You are who you eat

We have taken "down there" for granted for far too long.  Since the beginning of humanity 2 million years ago [since long before indeed], we have been toting around a couple of kilos of bacteria, mostly in our large intestine, but also up every orifice and on every epithelial surface.  Since the beginning of science 2 centuries ago, we have been studiously ignoring this ecosystem.  We know a helluva lot about trophic levels and population cycles on British chalk uplands, in New England ponds and across the Serengeti, but until recently we have been in the dark about our intestinal flora.  We have been utterly reckless over the last fifty years with the profligate use of antibiotics for trivial infections, let alone as growth promoters for chicken. Everybode kno that antibiotics don't work on viruses, but they are nevertheless widely prescribed for viral infections as a prophylactic against a secondary bacterial strike at the virus-damaged tissue.

Recently, the medicos (the brighter members anyway) have started to box a little clever rather than always using a kill-them-all broad-spectrum antibiotic.  If you can encourage the growth of good bacteria, then you can let them out-compete the bacterial black-hats.  It works, for example, in foul-water treatment plants. You can reduce the nitrate levels in sewage, and so reduce the eutrophication of natural water downstream, by encouraging bacteria to convert the nitrates to gaseous N₂ which disappears back to the atmosphere for another 100,000 years of inertness.  Which bacteria? Denitrifying bacteria, like Pseudomonas denitrificans and Alcaligenes denitrificans. How encourage?  By judiciously adding a carbon source to the treatment process; carbon is often the rate-limiting nutrient; adding a handful will cause a bloom of P. and A. denitrificans. A small eutrophication in the settlement ponds prevents a larger and less controlled one in the wild: neat! I've already reported on FMT - faecal microbiota transplantation as a solution to the frequently fatal infections by Clostridium difficile that are picked up in Western hospitals.  That's a rather zen-master solution, I find.

You could with advantage listen to the TED talk by Rob Knight, in which he describes some of the mind-boggling information that is emerging on the importance of our microbial flora for maintaining our normal health but also probably in setting a range of parameters for our mental state.  Apparently your attractiveness to mosquitoes is determined largely by the bacteria you host on your skin and the volatile chemicals they give off. It is not a huge leap to suppose that your attractiveness to sexual partners is driven by the same landscape. Inside, your intestinal flora determines whether the painkiller Tylenol is toxic to your liver or not.  What Knight's group have done is create a crowd-sourced project to sample the bacterial fellow-travellers of some 8000 different people and compare them with each other.  It's complicated and extremely data-heavy but if you apply some clever statistics you can identify trends in the genetic data - data which is based on perhaps 10,000 different species of bacteria in each of us with a combined toolkit of between 2 and 20 million different genes.  There are, for comparison, only 5,000 species of mammal across the entire globe.  The picture above right, shows the two major trends in the data.  Each dot represents a community of microbes from one of four locations (mouth, skin vagina, colon) in a few hundred individual human bacterial ferries. Two things pop out: 1) your oral flora is nearer to mine than it is to your own skin bacteria 2) Your oral flora is more distant from your vaginal flora than the ecological communities found in. say, the Serengeti compared to a Scottish Sea Loch. Neonates acquire an intestinal flora that looks more like normal vaginal bacteria . . . except if they a delivered by C-section, in which case their flora starts looking like normal skin bacteria. Mrs Knight's daughter was delivered by emergency C-section but they took remedial action to ensure that she the daughter was formally introduced to the vagina which she had bypassed in the birth-process. Why were they in such a hurry to slather the newborn in vaginal mucus?  Because the statistics suggest that Caesarian babies are more likely to develop asthma, eczema and obesity.  We'll come back to this story later, but right now you should see the TED talk!

Go easy on the antibiotics

Does MRSA put the frighteners on you? What about CRE?
Q. How do they make up these acronyms?
A. [Pick-an-antibiotic] + [R-for-resistant] + [pick-a-microbe]
You shouldn't worry unduly about these nightmare superbugs because you have probably been exposed before and your immune system is primed to deal with them as they present on a dodgy burger served by someone with poor food-hygiene. Your Aunt Jenny otoh going in for a hip-replacement really should worry because she is likely to come out in a box on account of there being a lot of MRSA about (up 30% of Irish noses) and Jenny is old and her immune system is slowing down. She needs a bit of help over-coming nosocomial (hospital-acquired) infection and we've squandered the antibiotic discoveries of Alexander Fleming and others by using them as growth-promoters in battery chicken factories.

That's bad, especially for Jenny, but largely in the past: we can't turn back the clock and limit the use of antibiotics to 'vital' treatment. Turns out that dosing infants with antibiotics may also pay forward in deadly coin by limiting the effectiveness of vaccination.  I say this because of some evidence about the interaction of antibiotics and antibodies in mice. Here blogged. Here the original Elsevier pay-walled paper. Remember that almost all of biomedical research works on the model of if it's true for mice it is quite possibly true for humans. First we'll have the Elsevier executive summary for the tweet-and-manga generation:

I'll develop that a bit because it may be important. What the group from SAHMRI, Adelaide have done is treat mother-mice and their offspring with oral antibiotics ampicillin and neomycin for different amounts of perinatal  time and then measure the quantity and diversity of their gut flora. Not surprisingly the flora took a hammering under the antibiotic regime [L]

• graph A at Day 21 the untreated NOABX pups have about 10,000x more bacteria in their guts than their ABX antibiotic treated litter-mates [it's on a logarithmic scale]. A week later, the effects of the bacterial holocaust are wearing off and the ABX mice have only 10x less bacteria. This is just counting bacterial bodies. 
• graph B shows that the Day 28 flora in the ABX group are recovering their numbers but are seriously adrift wrt their diversity. After the antibiotic treatment, certain species of the remaining bacteria get off to a flying start, seize all the best places in Café Coliform and leave only crumbs for the less assertive competition.  Exactly who gets gets there firstest with the mostest is a little unpredicable - it is chaotic [sensitive to initial conditions and random chance] at the start of the race.

The gut-microbe situation [imagine a human home with a septic infant who has been treated with augmentin] will get back to something approaching the status quo ante in time because the sibs, the parents and the family dog will be liberally sharing their bugs with the wean as s/he recovers. That's all very academic, and you might be tempted to cry So what? Particularly if you haven't read my report on how gut Lactobacillus is a key cog in the chemistry of maintaining blood pressure.

Blood pressure is important but Lynn and Co from SAHMRI are in the business of controlling pathogenic infection in children. If you don't survive to adulthood because you've been whacked by infectious diarrhoea, malaria or TB, then a healthy blood pressure in middle age is moot. They are convinced that vaccination is a key element in boosting the immune response to pathogens. What if, they wondered, the normal gut flora is an element in ensuring the efficacy of vaccination. Many vaccines have adjuvants, like Alumina, which work by geeing up the immune system to recognise the added pathogen but nobody really knows how adjuvants work. IF there are 10,000 species of bacteria in the normal gut each making several thousand proteins contributing to several hundred biochemical pathways ANDIF this complex eco-system is managed by our immune system (so we don't die or have persistent coughs or spend hours on the toilet) THEN maybe the normal flora is relevant to the response to vaccination.

Team SAHMRI did a lot of parallel experiments testing the response to BCG [TB]; meningococcus B (MenB); meningococcus C (MenC); pneumococcus conjugate vaccine (PCV13); and the INFANRIX Hexacombination vaccine (Hexa) which contains antigens from hepatitis B, diphtheria, tetanus, pertussis, Haemophilus influenzae B, and inactivated poliomyelitis virus (IPV). All of which are routinely applied to tiny Australians. They found that, in almost all cases, after vaccination there was more immunoglobulin G aka IgG circulating in the antibiotic-free mice than in those treated with antibiotics before vaccination. I've shown the data for menC [L] which shows neither the clearest nor the noisiest difference between IgG concentration in NOABX vs ABX.  Production of pathogen-specific IgG is known to be a key element in the immune system's response to infection. There is lots more belt-and-braces experiments described in the paper including a rescue of the flora in ABX mice with a fecal microbial transplant FMT, which has been shown to be so effective against C.diff. But I won't overwhelm you with details - you'll have to pay Elsevier for them. This-all suggests strongly that a course of antibiotics in first months of life may adversely affect the subsequent response to vaccination. Ho hum parenting is so damned hard: you take the kidder to the doctor because she has ear-ache and she gets a course of antibiotics. You-the-parent would never think that this action to spare your baby pain will be responsible for a gruelling bout with the whooping cough two years later because the pertussis vaccination didn't take.

Full disclosure note: David Lynn did his PhD in St Vincent's Hospital under my co-supervision. My supervisory style was similar to the way we allowed Dau.I and Dau.II to educate themselves at home: "shut up and get out of the way". You can see how effective this strategy can be, because The Boy Done Good.

Over the hill? Not!

Writing about "the delicate folds and subtle colours of the reproductive parts of some plants" last week made me think of  W. Keble Martin about whom I wrote this trib as the vicar who drew a year ago. There I characterised him as "not an idle sort of chap and spent every available hour hunting out ordinary and rare plants and recording their distribution".  I now know that the key word in that sentence is available because years would go by when Martin drew nothing at all because he was busy with his day-and-night job as a vicar and rector of the Church of England. I know this because I just finished a sequel to The Concise British Flora in Colour called Over the Hills, which is available super-cheap on Amazon.  His Concise Flora was hawked around numerous publishers who saw the colour plates as only a cost and not an opportunity and refused the project. When it was finally published in 1965, Martin was 88 and the book became a publishing sensation which shifted 100,000 copies before Christmas that year.  It cannot have been only because there was a foreword by the Duke of Edinburgh. Hoping to net some more profit from the tsunami of petals, Michael Joseph asked Martin to write an autobiography which came out in 1968. For those of us nearing retirement, we may note that when Martin resigned his last parish at the age of 72, he still had 20 years of active life - and a second marriage, the old dog - ahead of him.

Keble Martin was born in 1877, the first drawing for the Concise British Flora - of snowdrops Galanthus nivalis - was made at Dartington in 1899 while he was waiting to go to theological college. He was still tricking about with the drawings 60+ years later. Some of them had to be traced and redrawn to get them onto better quality paper, some suffered from fading of colours and he had to re-label all the early work when he realised that English common names wouldn't answer any more, and he relettered everything as Linnaean binomers. Indeed, he lived through the period when Latin came to be acknowledged as the universal language for clear communication.  Don't get me wrong, in my tribs to An Englishman's Flora I've delighted in the diversity of names which ordinary people attach to flowers in their local world. But we no longer spend our entire lives living in the same parish and we may need to talk about snowdrops with Hungarians [hóvirág - lit. snow flower] or Germans [Schneeglöckchen lit. snow-bell]. On the back of his Flora, he was invited to submit four designs for standard-rate postage stamps; they [see R above] were published in 1967. The design included "Keble Martin" the painter and "Harrison" the printer in small print but neglected to include any ID for the flowers themselves - neither English nor Latin. I guess that's because each design included several species and a complete inventory of names would fill the stamp on their own.

An Englishman's Flora

It's a strangely connected universe is the interweb. On the 6th November I mentioned an old flora that had intriguing and evocative lists of common flower names to supplement the rigid and rigorous Linnaean binomers by which biologists are required to refer to their favorite species.  I spent an hour or so trying to track down a proper reference to this book but to no avail. Nine days later I was whacked upside-the-head by this review of Geoffrey Grigson's An Englishman's Flora. It was obviously the same Flora! Although it's not nearly as old as I thought, having been published, just, in my lifetime. That evening I ordered up a 1996 reprint on Amazon and it arrived, by a tortuous route, in my hands less than three weeks after I'd been memory-prodded about it after decades buried in my head's increasingly inefficient filing system.  Well it's just wonderful and, if you live in these WEA islands and have the least interest in etymology or the living world, you should secure your own copy ASAP.  Cheap enough second-hand on Amazon.  Two of the thre
e plants which I'm singling out today are named officianale, which means of the [apothecaries] office: they were known/believed to be pharmacologically active.

As I promised you by implication, the common names of the dandelion Taraxacum officianale, I'll write the whole list here. As Grigson says about another wordier entry, the longer the list the more likely that the plant was noticed for its, real or perceived, functional uses (pharmacopoeia, cosmetic, poisoning your father-in-law, causing sickness in your livestock). Bitter Aks, Bum-pipe, Burning Fire, Canker, Clocks, Clock-flower, Clocks-and-watches, Combs-and-hairpins, Conquer more, Devil's Milk-plant, Devil's Milk-pail, Dindle, Dog-posy, Doonhead clock, Eksis-girse, Fairy clock, Farmer's clock, Four o'clock, Golden suns, Heart-fever grass, Horse gowan, Irish daisy, Lay-a-bed, Lion's teeth, Male. Mess-a-bed, Milk gowan, Monk's head, Old man's clock, One o'clock, One-two-three, Pee-a-bed, Pss-a-bed, Pissimire, Pittle bed, Priest's crown, Schoolboy's clock, Shepherd's clock, Shitabed, Stink Davie, Swine's snout, Tell time, Time-flower,, Wee-a-bed, Wet-weed, Wishes, Witch's gowan, Yellow Gowan.  The name that's familiar to you in Somerset will baffle your cousin from Northumberland, even though you both speak English - that's why we have the Linnaean binomer.  Some of the names are readily understood: the white sap looks like milk, all parts of the plant are diuretic, the bald receptacle after you've blown the seeds off (to tell the time) looks like a tonsured head . . . if the owner has had the smallpox.  Gowan is a Scots/Lallans word for any white or yellow field flower.

Dandelions are ubiquitous: found in all 112 vice-counties of Great Britain [see R] and all 40 in Ireland. A vice-county is a broad stretch of country with similar habitat. They are based on the old Local Government Act 1888 counties, so Wales is probably over-split.  Scilly gets binned with West Cornwall but the Isle of Wight gets its own. But the peony Paeonia mascula is found in only one vice-county and but a tiny part of that which is a 20 hectare island in the Bristol channel called Steep Holm. [Jakers, we're back to islands again] It is administered by Avon County [Bristol to you and me] while its neighbour, 5km North, Flat Holm is called Ynys Echni because it's under the Welsh flag.  As for the peony, it is a mystery as to how it got to this one isolated location so far North of its Mediterranean range. Botanists have gotten all exercised about whether it is native to the area or introduced and doubtless they have some rules for distinguishing among a) appeared after the ice-sheets retreated after the last glaciation b) was planted by an unknown herbalist when monks briefly inhabited the island in the 13thC c) fell out of the pocket of a Napoleonic era visitor.  It's barely 'there' in any case - growing in two clumps halfway up the cliff-face.

In the New Forward to the 1996 re-issue of An Englishman's Flora, Sophie Grigson the telly-cook [and his daughter] waxes lyrical about the comfrey Symphytum officinale fritters that her Dad used to cook up for the family.  Hmmm, very nostalgic but perhaps not such a good idea because comfrey is a known carcinogen in rat livers probably because of the high titre of the pyrrolizidine alkaloids [like retronecine, structure shown right] in the plant.

Flora de Yola

It's been months since I schlepped 40km SE on a Tuesday evening to do Wexford Science Café. It's so easy to get slumped on a sofa after tea. The May meeting, however, billed Paul Green from Ballycullane who has recently published (2022) his compendious Flora of County Wexford. Is there a better way to display the book than next of a clump of cowslips Bainne bó bleachtáin Primula veris in our front yard? eeee but I do love an expert - they can be so obsessive: and so, reader, I went.

I came away with some insight into what it takes to record all the plants in a given area. And 'area' is fractal; you can like Louis Agassiz get up close and personal with all the beetles in your back yard or you can go global like Phoebe Snetsinger clocking off 8,300 different birds before she died in a car-wreck in Madagascar. Green has split the difference: his checklist is the 2,558 monads of Co Wexford. That's larger than the official 2,367 km² area of the county because of the fringe of monads shared across the county borrrder.  A monad is any 100 hectare 1km x 1km square on the official Ordnance Survey grid which maps the county.  Naturalists also respect tetrads [a block of 4 monads] and hectads [a 10km x 10km region]. The whole island is overlain with a grid of 25 lettered 100km x 100km squares; most of Wexford being in squares S and T. 

Except on the open heath and moorland of the Blackstairs, pretty much every monad in Wexford is traversed by a public road. This is of great benefit to folks whose task involves checking off data on a clip-board containing a species list. Farmers, in general, are hostile suspicious about The Man checking up on their business especially if their own paperwork is perhaps sketchy. This introduces a bias: plants which like gateways and roadside verges are just more likely to be recorded than those which hug river-banks or thrive in the middle of pastures - it's the access innit?

So there I waszzzzz paying attention to the war stories of botanists in search of red-list rarities, when up pops a picture of a small Church of Ireland and its yard - they all look alike but this one was tinkling bells of family familiarity. It turns out that my grandfather's final resting place in Saltmills is the Go To place for orchids especially the green-winged one Anacamptis morio. The botanists have begged the parish not to mow the churchyard in May - when this orchid flowers and sets seed - but the parish is on autopilot for keeping the grass trim - protestants gonna protestant. Heisenberg's observer effect whereby the act of recording something affects its existence should encourage botanists to observe but not intercede but it's right difficult to let nature take its selective course. I gather that some patches of rare plants are reseeded occasionally from seed-banks in the National Botanic Gardens Garraithe Náisiúnta na Lus in Glasnevin. But I don't have a dog in that fight.

There are 850 different species of flowering plant in Ireland. Wexford, like most Irish counties, I guess, sports about 150 species per monad. Obviously, some species will be omnipresent while others will be clinging by their sepals in only one place. Linnaeus decided that the easiest way to definitively ID plant species was by considering the details of their reproductive parts. But flowering may happen at pretty much any [species-specific] time of the year except dead winter. Accordingly, a full survey requires visits in at least Spring, Summer and Fall if not every month. But each monad will occupy the recording angel for 1 to 3 hours, and they must go cross-eyed with the effort after a while. At two monads a day, six days a week, 40 weeks a year, it will take 5½ years to cover each location once. And who pays for petrol, let alone botanist-time? All told such a project, done properly, might cost €500,000 in billable hours and expenses. There is a reason why such Flora projects - which generate data essential to documenting the ecological status quo and thus getting a handle on The Future in a climate changing world - have been traditionally carried out pro bono mundo by vicars who have little to do between Sundays and elders who keep active in body by being engaged in mind.

It is notable that Wexford is, botanically, the best covered County on the island. The vast majority of the work has been carried out by Paul Green and his comrade Paula O'Meara neither of whom are inclined to let mere weather rain upon their parade of data. Hats on! - another lashing shower coming in from the West. Paul Green used to blog about his Wexford project. If there is a second edition of this Flora of County Wexford could someone take a leaf out of Geoffrey Grigson's An Englishman's Flora [bloboprev] and include the Irish names? There are only 800 species on the list! You may start here.

The vicar who drew

A bit more respect here, please! We treat of the Archvicar of Haccombe. Haccombe is one of the smallest parishes in the Church of England and the incumbent priest has, since 1315, the unique CoE distinction of being an Archvicar answerable only to the Archbishop of Canterbury. Where is Haccombe? Just North of Coffinswell, [see map R] another microscopic benefice both about 3km outside Newton Abbot in SE Devon. In 1921, W. Keble Martin was offered the benefice of the combined parishes of Haccombe [Archpriest] and Coffinswell [Rector] and he lived and worked there for 13 years until he was promoted to the parish of Great Torrington, in N Devon. Great Torrington is, by comparison, huge with a population of more than 5,000 people. Rector has higher status than a mere vicar because the parish supports him, while vicars get money from the diocese. I get the sense that this easy job was a reward for having paid his spiritual taxes in a series of rough urban parishes in the North of England and then serving as a padre [the title given to any man-of-the-cloth in the armed forces] in France during WWI.

Keble Martin was not an idle sort of chap and spent every available hour hunting out ordinary and rare plants and recording their distribution. His interest in plants grew out of a youthful enthusiasm for moths when he wanted to know which plants served as food sources for his favorite lepidoptera. In 1939, he published the definitive Flora of Devon at the age of 62, as the storm clouds of WWII grew heavy with dread. You can pick this book up 2nd hand - to you, madam, a snip at £86! To record what he was looking at, Keble Martin drew each specimen, often digging up a representative plant to bring it home, but being careful to trek the thing back to its original habitat when he'd finished. In The Institute we have a debate about whether students should be required to draw what they see or just snap it with the smart-phones. If you draw, you can picking out the salient [we don't use that word, of course] features which are key to identifying the species, a photo can become just another smudge of green. otoh, a drawing can introduce an unwelcome sliver of subjectivity into the record. Drawing forces you to consider the thing you're looking at. ANNyway, Keble Martin drew and coloured beautifully and he was persuaded to publish The Concise British Flora in Colour in 1965, when he was 88! As it says on the tin [R showing the dust-jacket], this flora illustrates nearly 1500 different species, in a series of gorgeous plates each faced by a page of short paragraphs describing where you can find each represented plant and defining details of what it looks like. The drawings represented 60 years of careful observation. We used the book a few weeks ago to identify a strange plant in our hay-field:
Rinanthus minor L. Hayrattle
Less robust; branches short; leaves crenate; intercalary none; corolla 15 mm.; straight; purple teeth broader than long; lowest bract teeth less deep; Common in pastures on basic soils. Flo. May-June.
Hmmmm. We're probably wrong on that, so; because our soil is the opposite of basic. Maybe we had Rinanthus serotinus Oborny Greater Hayrattle. Better check things out next year when they are in flower again.
The Concise British Flora in Colour was a huge best seller: my father was one of 100,000 people who bought a copy 50 years ago.  That's good because the price is as low as £4 on Amazon. Make a suitable gift for any British teenager you know: get 'em off their devices and out getting their knees wet in the grass.

If you look carefully at the map [top R] you'll notice the Plant World Garden Centre exactly midway between Haccombe and Coffinswell. It's called Plant World because the 4 ac = 1.6 ha. site incorporates a floral map of the World [aerial pic]. The proprietors, Ray and Linda Brown, have made some effort to grow Asian plants in Asia and so forth, which I think is a nice conceit. If you visit, you can buy plants and seeds as well as a ploughman's lunch and a cup of coffee. But I can't find any acknowledgement of the geographic connexion with W. Keble Martin; that is a missed opportunity in my opinion.

Bugging the uterus

I grew up as a geneticist and evolutionary biologist,  at the top of my modest game when analysing DNA sequences on a computer. I was safe there, although a disaster in the lab. Then about 15 years ago I got a billet in a comparative immunology lab on the theory that my expertise could bring a needed new dimension to their research.  It was hard for everyone because geneticists go all weak at the knees with B-cells, T-cells and dendritic cells and affect to be unable to understand the difference between CD4 and CD8 and the other proteins which coat the surface of these immune cells. Immunologists, on the other hand, have a model where CD4 and CD8, and the other proteins poking out of the membranes of cells, are just there without ever reflecting that they are there because of the DNA in the cell's nucleus.

I have a long-standing interest in microbiomes: the invisible freight of bacteria on which a lot of our health and happiness depends. The intestinal flora is one such ecosystem which you should cherish with kale and strawberries straight from the field. If you wage war down there with oral antibiotics for an earache, then you can get yourself in serious trouble with Clostridium difficile or worse.

Now here comes an interesting study of the uterine microbiome which gives a clue about two of the great immunological mysteries of mammalian reproduction.  The first is the miracle of bearing young at all.  Birds get their eggs fertilised and then unload them in a convenient hard-shelled package where they continue their development until hatching.  Mammals otoh hold these ever growing cluster of 'foreign' cells inside.  Immunity is all about recognising the difference between self and non-self.  The embryo may have half its genes in common with its mum but the other half is clearly foreign, yet women tolerate this interior growth for nearly 40 weeks.  If it was a tumour (which is much closer genetically than a fetus), the mother would be f**ked.  Lots of people have theories about how this tolerance is achieved but we're still short of data and evidence to clear up the conundrum.

The other mystery was mostly in my head and hinged on a false premise. If the uterus is effectively sterile and delivery is such a one-way ticket, then how come so many cows get endometritis [inflammation of the uterine lining] immediately after birth.  This is a major cause of bovine infertility and so economic loss to the dairy industry.  I was wrong about the sterile uterus.  Like every other warm wet place about us, bacteria like to set up home there. Endometritis occurs when the balance among the uterine flora changes with the disruption - physical and hormonal - of delivery.

It turns out that the uterine flora is more similar to that in the oral cavity than the wild bunch in the vagina next door.  I've shown that oral, fecal and vaginal bacteria are as different from each other, despite being in the same person, as the ecosystems of the Serengeti and a Rwandan jungle are different despite being on the same continent.  For a long time we couldn't get a handle on the microbial diversity in real ecosystems because swab we might but most bacteria have never been grown on a Petri dish and were effectively uncharacterisable because of this. Non-culturable bacteria are no longer invisible because of next generation sequencing NGS.  This allows researchers to pick up a mess of potage, give it a good whizz in a Moulinex blender and then sequence all the DNA. In particular they tend to pick out all the 16S RNAs which will tell them what sort of bacteria were present in the sample before they were turned into soup.  We have, for example,  the complete sequence of Neisseria meningitidis, which can be grown in the lab. If they pull out similar but not identical 16S RNA they can surmise that Neisseria unknowniditis is present. And the researchers can even get a quantitative estimate of what's present.

The paper gives a really interesting insight into the complexity of microbial interactions.  Several adverse conditions including premature birth depend on (are caused by) the presence of more than one species of microbe: it's the interactions, stupid. But normal full-term pregnancy seems to be mediated by the bacterial flora of the uterus as well. The solution to the mystery of pregnancy may well lie with our beneficial bacteria.

C-sections for all

. . . those who wish to dice with a hospital-acquired infection. The rate of C-section in Ireland, at ~30%, at the high end among Western industrial nations. And it's not a First World solution / problem, Dominican Republic, Brazil, Egypt, Turkey, and Venezuela all have more that 50% of delivery by scalpel. The absolute numbers of caesarian births has doubled since 2000; the rate [12% in 2000 to 21% now] not quite so much because nobody is dying any more and the total population is up 1.5 billion people in that short time. What differ? Labour is so called because it is hard-work: certainly for Mum because she can remember it but it can't be easy for the emergent one, either. If modern tech can bypass the whole messy business and everyone survives, what possible harm?

Well a recent paper in Nature is not beating about the bush [so to speak] Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth in characterising and following up just under 600 full-term babies: 314 vaginal births and 282 C sections.  It's part of the Baby Biome Project BBC; Sanger Centre. The thing is that, unless something has gone seriously wrong there are no bacteria within the amnion - the fluid filled bag in which the foetus develops; obtaining the nutrients to do that development via the placenta and umbilical cord. The mother's skin, her vagina, let alone the nearby rectum (leaking a little as push comes to shove) are, by contrast, home to a rich variety of microbes. Not the same chaps in each niche, however: each place has a characteristic and different family of bacteria.

With an old style vaginal delivery, the new born gets a a good mouthful of his mother's microbial flora, either directly or as soon as he starts sucking his thumb or his mother's breast. Babies delivered by Caesarean section do in deed get a dose of bacteria but they are much more likely to be those typical of hospital acquired infections. The researchers have to an extent controlled for this but the fact that All C-sections are followed by broad-spectrum anti-biotics (as a prophylaxis against infection through the incision) is another variable that drives the neonatal flora towards the bad bacteria. And while I am definitely pro-choice, mothers who plan on a C-section followed by Nestlé powdered cows milk with or without melamine should really read the details of these comparative outcome studies. There is a huge difference in the quality of the child's intestinal flora when measured 4, 7 and 21 days after delivery . . . but when sampled in "infancy" = 9 months later, everything looks like it's evened out between the two modes of appearance:

Down in the dark

Classes started at The Institute on the 11th September and the next day I gave my Pharm Tech the How much do you know? Human Physiology Prequiz. As in previous years only a third of ordinary adults know their guts well enough to correctly order the different sections: Appendix - Colon - Duodenum – Esophagus – Stomach. Of course you can get through your whole life, and be a nett contributor to human health and happiness, without being able to name different parts of your body. But my data suggests that most people have a) no idea how the digestive system works [that's okay] b) no idea how it might work better [less okay if the goal is health and happiness]. This ignorance is appreciated beyond the confines of The Blob: it is explicit in the sub-title Giulia Enders book Gut: The Inside Story of Our Body's Most Underrated Organ; [Darm mit Charme. Alles über ein unterschätztes Organ] which I have finished reading.

I'm a professional biologist, so I can't remember a time when I didn't know the basic arrangement of my internal wobbly-bits [diagram R]. Nevertheless, I'm continually learning new stuff, most recently about the importance of the intestinal flora. The Blob records microbiome 26 times apart from this mention and flora 62 times; and rarely as a girl's name. I reckon I'll have more to say on our intestinal co-workers in the future.

On farts. One phrase I've never used before is sphincter ani internus SAI - because I'd never heard of it until Giulia Enders kicked off her book with a discussion of its value. Those of us who maintain some semblance of bowel continence are aware of the sphincter ani externus known to his pals as sphincter ani. When we grow up enough to stop having a accident downstairs we have achieved conscious control of when to open [rarely] and close [mostly] this little ring of smooth muscle. Actually it opens rather more often than when we are sitting at stool because the active microbial flora is producing quite a lot of gas methane and carbon dioxide mainly with a touch of hydrogen sulphide if we've been eating eggs or cabbage. The SAI is a sampler gate-keeper and every so often opens up to allow a sample of gut contents into the ante-chamber of outside. IF that sample is a bubble of gas ANDIF we are not having tea with Great Aunt Gwendoline THEN we can let rip; ELSE NOT. If the sample is more substantive we need to find a toilet - OR the woods IF a bear. It is not only 12 y.o. boys who find a darn good fart to be immensely satisfying. Or dangerous: methane fart deflagration; not the same as a BLEVE. Are you still a 12 y.o?

On sitting at stool. As we get older all the subtle, intricate, multiply-redundant systems of human physiology start to become more erratic: blood-pressure more variable; blood-sugar less reliable; brain function sketchy; bowels sluggish. In Ireland we have adopted a standard toilet which makes it much less easy to have a good crap; compared to all them foreign johnnies who squat to defecate. Squatting puts all the poo-ducks in a row making evacuation of the rectum a bit easier. You can do it sitting on a throne that is 450mm higher than your heels but you are making it more difficult for the poor old bowel. Ironically, as having a good shit become more difficult with age, some dogoodnik carers will actually raise the height of the seat to make it easier for dear old dad to get up and down to it with his enfeebled leg muscles and degenerate sense of balance.

<over-sharing alert>I have taken this Giulia Enders analysis on board and am experimenting with a little step (330 x 330 x 80 mm & made from a square of polystyrene: previously the lid of a biological-sample cool box) to raise my feet and make the experience more squatty.</over-sharing>. There are probably 1,000s of elderly British and Irish folk who are forking out for Movicol or Senokot.; when foot-shelf 10 or 15cm high in front of the jacks might do the trick.

Here's a TED Giulia Enders preview or an exec summary.

Other women in science.

Shit storm

Clostridium difficile infection is the very divil [prev], not least because they've renamed it Clostridioides difficile. It's more familiar as C.diff because few can pronounce the difficile - me I prefer it as Italian diffíchilleh. It is 'difficult' because very hard to shake if once it takes hold of your gut. Much better not to get it at all but a) people with a healthy gut flora will often harbour manageable quantities of the bad boy b) the most common route of infection is nosocomial - in hospital - where / when your flora has been cleaned out by a regimen of antibiotics to treat some other infectious disease. Then it turns out that C.diff is resistant to every other antibiotic in the hospital's medicine chest.

FMT has been one of the most unexpected, most wonderful, most appropriate technology solutions to the difficile problem. The idea behind fecal microbial transplant FMT is that my intestinal flora - the whole community down there in the dark - is able to keep C.diff in check . . . so what say we throw in the whole microbial black box and see what happens. Miracle happens: within days the symptoms - bloody watery frequent diarrhea, heart racing, abdominal cramping, fever, nausea, loss of appetite - subside and disappear permanently. Nobody knows how it works - and FMT only really works for C.diff  it's no good for bowelly shite like IBD, Crohn's, ulcerative colitis: let alone for depression, autism, multiple sclerosis or Parkinson's. As 10,000 people shit themselves to death from C.diff  each year in the USA alone, it's hard not to like FMT. And since it was given an experimental licence in 2013, some 50,000 people have been treated many of them successfully. Obviously it depends on the quality of the fecal matter and there may well be horses-for-courses compatibility issues. I guess there are sooper poopers out there whose discard is as keenly sought after as Premier Cru Bâtard-Montrachet.

The FDA and EMA, the regulatory authorities in the USA and EU respectively, are deeply ambivalent about FMT. They want to licence any efficacious therapy, yes, but they also want to have quality control and that requires a) purity and b) the vendors knowing what's in their product. Then again, they really want to licence a few commercial [accountable, quality assured, protocol following] products because there are too many people who are doing the transplant themselves in the utility room. They say that all you need is a blender, a sieve, some clean water and a turkey-baster. Yes yes, that same turkey-baster which your lesbian pals used to get pregnant two years ago. And yes yes, they put it through the hottest dish-washer cycle twice.

Now the FDA is reporting a dark lining to this silver cloud with half a dozen cases of people who got sick after FMT. Seems that there have been 2 cases of enteropathogenic E coli (EPEC) infections, while 4 people came down with Shiga toxin–producing E coli (STEC). All the FMT doses involved came from OpenBiome a Massachusetts supplier of quality poop. This is a profitable non-profit turning over €7,250,000 in 2017 - there are six executives on six-figure 'compensation'. That same year they shipped ~10,500 treatments from their stool bank. For the last couple of years, I've been supervising MSc students on our Pharmaceutical Regulatory Affairs [Pharm-Regs] course at The Institute. From reading about and discussing the differences between Europe and America, it seems that the EMA is rather more risk-averse; while the FDA more utilitarian: being prepared to tolerate some shit happening, if the overall benefit is positive. I can't see them closing down the authorised supply-chain because 1/1000 of the products is contaminated with over-aggressive coliforms. The benefits - medical, psychological, economic, social - of having a workable treatment for C. diff outweigh the costs. If the FDA can hold their nerve and OpenBiome can up-grade their screen protocol then these 6 adverse outcomes will fizzle out to a storm in a tea-cup.

Go Nobó

I do so have friends. I do have social life. There is life beyond The Blob and The Institute. An old friend from London had Irish business to transact in Kinsale and took a lay-over in the Sunny South East for the weekend. We got invited to dinner, which we ate outside watching the Sun set over Bannow Bay. As you might expect when wrinklies get together, the talk was about retirement, pensions and grandchildren but also about the diminishing store of aged parents. Like the boys night in, which I've been passing with 91 y.o Pat the Salt each Sunday evening since February, one of my pals goes up to Dublin every week to spend the night with his widowed mother and sleep in the bedroom that he ceased to occupy more than 40 years ago. He fixes dinner, fixes the gutters, and they might go shopping together while he's there with the car.

A few weeks ago, knowing her fondness for ice-cream, he saw a tub of Nobó ice cream in the freezer section and popped that in the basket. A week later, he was back home and asked his Mum how she enjoyed the Nobó "Oh, I didn't like it at all, dear, I threw it away". Ho hum, I guess the older generation [I soon won't be able to use that phrase, as our parents shuffle off and my generation steps up to the plate for the final play of the game] is quite conservative in their tastes. Isn't it also true that as we age, our taste-buds fall off, and we're reduced to requiring a snow of salt and/or lashings of sugar to taste anything at all at all.

On cue  last weekend, along with fruit crumble dessert, a little tub of  Fresh Lemon Nobó made its appearance, along with Créme Fraiche and plain yoghurt. When we were all growing up in the 60s, none of that would be available, except the fruit crumble, which would have been served with either

• a ferociously yellow [prev yellow confection] gloop made from milk, sugar and Bird's Custard Powder [cornflour + colouring]
• fresh cream, possibly whipped
• plain vanilla ice-cream which would have been flat white in Ireland or pale yellow in England

We've come a long way in 50 years: milk treated with many different species of lactic acid bacteria has raised the variety of dairy products available in Ireland from milk, butter, cheese [two sorts only: red and white], cream and buttermilk. All the extra LABs makes life more interesting and possibly, just possibly, improve the make-up of our intestinal flora [actimel etc.].  But with the increased choice, there has been an epidemic of neuroses about food. It seems that more than half our tree-hugging friends are lactose or gluten intolerant or both and must have more expensive alternatives to ordinary bread and cheese.

There is no doubt that gluten intolerance exists. It is an auto-immune pathology called coeliac disease and can cause distressing feelings of bloating and abdominal discomfort because the intestinal flora cannot handle certain of the wheat storage proteins. I've never heard of anyone dying of coeliac disease although the symptoms are persistent and no fun. There may even be a coeliac "epidemic", in that the incidence seems to have increased up to 5-fold over the last 50 years. But that's from a very low base: was 0.2% in the USA, now scraping 1%; and up to 3% in some Scandinavian countries. This could be more diagnoses as parents and GPs get to recognise the symptoms and/or it could be a 'real' increase driven by changes in the weaning pattern in The West. Or from the wholesale turn-over destruction of the gut flora with repeated doses of oral antibiotics for sniffles and ears ache?

There is far better evidence that lactose intolerance exists, indeed it is the norm in human adults. From an evolutionary mammalian perspective, milk is a super food for infants: every dietary requirement from 0 to 6 months supplied in a one-stop stop. After about six months - as the teeth start to erupt! - the poor old breasts are no long sufficient to supply the growing monster, and extra food needs to be supplied. Lactose, milk sugar, is a disaccharide, as is sucrose, cane sugar, but it consists of glucose and galactose rather than glucose and fructose. Lactose is sweet and delicious but requires an enzyme called lactase to break the bond between the two mono-saccharides as the first step in converting everything to glucose which is the basic internal sugar currency for mammals. In the normal development of most humans, the genes that go to make lactase are switched off when they are no longer required shortly after weaning. In a few human cultures, 10 or 20,000 years ago, some bright spark had the idea of domesticating certain artiodactyl species - cows, sheep and goats mainly - and feeding on their nutritious mammary exudates.

This cunning plan would have come to nothing without a co-incident mutation in the upstream control region of the lactase genes. Instead of turning off in childhood, this mutation allowed the persistence of lactase into adulthood. Lactase is only 'expressed' in certain cells along the lining of the small intestine which leak the material into the lumen of the gut. But only in these cells in some individuals. The map [R from UCL] shows that there are 3 foci where this mutation is at all common: Northern Europe, West Africa and the Middle East. In Ireland pretty much everyone - code red on the map is >90% - can convert milk sugar, and Chicago policemen with lactose intolerance are exceedingly rare.  If you're Chinese, say, or Ashkenazi Jewish or a !ung bushman from the Kalahari, you really shouldn't try ice-cream as you'll find it is 'too runny'.

I know one case of milk allergy, which is different from lactose intolerance, this chap's lips puff up at the least touch of dairy like people who are peanut allergic. Allergic reactions can be fatal and should be taken very seriously. In Ireland, the genetic epidemiology suggests that almost all of the half of my Irish friends who are faddy and demanding in their diet are really suffering from a First World problem. They should try spending a few months in an Ethiopian refugee camp where the EU is unloading its powdered milk lake and wheat mountain. It will be like a medieval witch trial, the true coeliacs and Jews will die, and the neurotic will come back to eat buttermilk scones like the rest of us.

Mais revenons nous a nos Nobós. Nobó, like Deliveroo, was gestated in NYC where everything is available !instantly! but born in Ireland: the brain child of Rachel and Brian Nolan. They are young and hip and media-savvy - nowhere on the Nobó website, for example, does it mention their last name: surnames are for old people. As we've seen above, old people are not the demographic for Nobó. Like Deliveroo, the website is slick and band-width heavy: movie clips, big graphics, luscious pictures and engaging style. If you're accessing the web from a dial-up in Bangalore - if you work in the call-centre for an Irish insurance company, say - then you'll get a lot hungrier before you download the information about a local stockist. But $2-a-day men are not the demographic either.

It will be really frustrating for the fellow in Bangalore because after the long wait, there will be no local stockist because as of this week, Nobó is only available in Ireland, and a handful of outlets in the UK including, conveniently close to Dau.I in Stroud, one in Cheltenham: Wholefoods, Gallagher Retail Park, Tewkesbury Road, Gloucestershire, GL51 9RR  . . . and a rash of them in the United Arab Emirates [all located on the zoomable stockists map so you can pick up the nearest Nobó-shop from your smartphone]. Four in the vicinity of the Dubai Marina for example [L].  I guess either Brian or Rachel has an enterprising cousin out in the Middle East.

I make something of a blood-sport reviewing craziness in the food industry but I will say for Nobó is that the ingredients are pared down to the essentials. Ice-cream usually has a quite frightening table of contents: E-numbers, emulsifiers, guar-gum, stabilisers, colours. But this isn't ice-cream, 'tis a long way from cream it was r'ared, it's a new confection based on the saturated fats in coconut milk and avocado rather than on saturated animal fat and lactose. The product list is, currently, trim as well. Six varieties:

• Choc and toasted almonds
• Coconut Milk, Honey, Avocado, Cocoa Powder, Water, Toasted Almonds, Irish Sea Salt
• Fresh lemon
• Coconut milk, honey, avocado, fresh lemon juice 6%, vanilla extract, pure lemon oil
• Passion fruit and mango
• Coconut milk, honey, passionfruit 11%, mango 8%, avocado, vanilla extract
• Irish salted caramel
• Coconut milk, coconut sugar 13%, brown rice syrup, avocado, vanilla extract, Irish sea salt 1%
• Mint humbug
• Coconut milk, coconut sugar, brown rice syrup, avocado, vanilla extract, peppermint oil 1%
• Vanilla coconut
• Coconut-milk (71%), honey, avocado, vanilla extract (2%)

So they are quite within their rights to claim No Dairy, No Gluten, No Eggs, No Soya, No Refined sugar, No Colourings, No Stabilisers, No Nasties. Just a note of clarification. Coconut milk is not the thin grey stuff than slops about inside the un-cracked nut - that is coconut water. Coconut milk is made in a very similar way to butter. The white flesh is grated and heated up with water to release the saturated plant fat which floats to the top. It is viscous, white with a creamy mouth-feel.

I was persuaded to try a sliver of Nobó on my crumble on Saturday - I'm not an ice-cream fan any more, I ate too much as a graduate student. The Nobó was fine, a bit more like a sorbet than regular ice-cream but that's okay and probably healthier. The brand has won prizes, positive reviews and accolades but I cannot web-easily find out how much the stuff costs. It will probably turn out like when my sister-in-law complained about the price for getting the family's Land Rover Discovery serviced. The manager of the dealership responded "If you have to ask how much a Land Rover costs to run, Madam, maybe you should choose a different marque".

Wallace Line

As I said before, Alfred Russell Wallace was a much travelled person. After a trip up the Amazon with Henry Bates, he went East and cruised about the spice islands collecting a staggering number of species new to science.  He has something like 500 species named wallacei or wallacii after him; as well as craters on the Moon and Mars  - but those are just hat-tips: he never got that far from London. Joe Public knows him because he lit a fire-cracker under Darwin's couch by sending The Ternate Letter to the great man which contained the core of the latter's own Big Idea. Darwin lay on his couch reading for about 50 years after his return from his own mind-opening voyage on HMS Beagle. There was a huge incoming correspondence from all over the world describing weird and wonderful aspects of the biological world; including of course the above-mentioned Ternate Letter from Wallace.

The Theory of Natural Selection proposed independently by these two men was the cohering conclusion to several strands of wildly different data:

• The graded similarities among adults of related species: we look more like our dogs than either looks like frogs - it's the nipples, stupid
• The divergence of embryonic development: a 6 day whale fetus is almost indistinguishable from a 6 day bat fetus
• Trends in the fossil record
• Biogeographical distribution: that are no marsupials in Europe outside of zoos; the flora of Ireland is really similar to the flora of England and wildly different from Brazil's - the explosive difference shook European naturalist [Darwin, Hooker, Wallace, Bates, Huxley, Humboldt, Bonpland etc.]

Darwin was a little lax in documenting his specimens - all his Galapagos finches were labelled 'Galapagos' but the key insight was that each island in the archipelago had different species. Wallace OTOH became acutely aware of the of the geographical provenance of his burgeoning collection and he started to notice trends and patterns.  He has been called the father of biogeography because he really put that way of thinking on the map.

Actually, that's literally on the map, because as well as the hundreds of species named for him, he also 'owns' a chunk of the East Indies called Wallacea and the most famous, not obvious to all thinking people, boundary in biogeography  - the Wallace Line [R in a bold blue] which marks the end of Asia and the beginning of marsupial land.  It's not as black-and-white, on/off as the bold line implies and there's another Lydekker's Line which separates Australia and New Guinea from the smaller islands to the North and West. Wallacea is the tropical paradise between the two lines is the grey where the flora and fauna show both Asian and Australasian attributes.  Of course 'grey' is entirely the wrong word to describe the brilliance of life in the tropics.  Wallace's Line is quite unexpected - why is there such a shift in fauna between Bali and Lombok when the two are separated by only 35km of ocean? That becomes a lot clearer if you metaphorically drain the ocean to levels experienced during the ice-ages when the water was all piled up in mighty glaciers and at the poles. Even with the seas 120m below the current datum, there is still a deep wet cleft between those two islands marking the boundaries between the archaecontinents of Sunda [W] and Sahul [E].

Wallace was also remarkable for his longevity, dying at age 90 in 1913: a year an a half after Alfred Wegener published his iconoclast suggestion that the continents have been romping about the face of the globe crashing into each other and groaning apart. That's why you find marsupials in Australia and South America but not in Ukraine or Ireland. But everyone ignored Wegener until 50 years after Wallace was dead.

aspartame makes you fat

Nearly two years ago towards to Birth of the Blob, I wrote a comment on a poorly nuanced RTE report about the association between diabetes and 7up (and other sweetened soft drinks).  If true it needed to be stated in a less hysterical fashion to convince me.  One of the factors that tuned my skepticism antenna was the fact that diet coke appeared to make you even fatter than regular sugar-loaded soft-drinks.  Although, when the increase in diabetes was properly contexted by BMI, the apparent association disappeared.  Turns out I was quite possibly >!gasp!< wrong . . . to think that aspartame and saccharine were irrelevant to the obesity epidemic.

It's all in the microbiome, stupid: the 10,000 species of bacteria that we all tote around with us, mostly in the large intestine.  On 18th September last year, there was a nutrition report which laid out some pretty convincing evidence that drinks loaded with artificial sweeteners, far from being a solution to our increasing girth might actually be making things worse.  Check out the work of Eran Elinav from the Weizmann Institute in Israel. Elinav at the movies!  One of the early (that's as long ago as 2006!) studies searched for twins, identical and fraternal, who differed primarily in trouser size. They took twin-paired samples from the twins' intestinal flora and introduced them into germ-free (caesarian-sectioned, brought up in a bubble eating gamma-irradiated mouse-chow) genetically identical mice.  The mice receiving the 'obese' bacteria reliably ballooned out, while their cousins who received slim bacteria gained weight at half the rate.  Why is this important?  Because we have in the last 100 years developed an epidemic of "metabolic disease" - a syndrome involving the woes of Western society: obesity, diabetes, fatty liver, high blood pressure and heart disease.

They have now done similar controlled experiments with mice getting artificial sweeteners in the water and mice getting glucose.  The mice taking saccharine.etc. rapidly developed glucose intolerance.  If you experience the following symptoms and are not recovering from a night on the batter, you might consider seeing your diabetologist:  Feeling very thirsty; Dry mouth; Extreme tiredness Blurred vision; Drowsiness; Frequent need to urinate; Loss of muscle mass.  Glucose intolerance essentially means that glucose doesn't get cleared from the blood circulation quickly after food intake but hangs around rather than getting converted into glycogen for future use. Apart from anything else, glucose is a universal currency and you are much more likely to develop septicaemia if you are hyperglycaemic - peripheral gangrene, anyone?  Convincingly, this glucose intolerance evaporated when the mice had their intestinal flora eliminated with a short course of broad-spectrum antibiotics.

Perhaps the most important factor that has developed from Elinav's huge sampling of people, their lifestyle, their circulating glucose levels and their microbiome and cross-referencing of these different threads (or tsunamis - we're talking terabytes of information, here) of data is that Folks are Different. The Atkins diet may work a charm for that lady you met at the water-cooler . . . and her sister; but will do nothing at all for you because your bacteria are not her bacteria. When I was working in St. Vincent's Hospital a dozen years ago, we were just beginning to talk seriously about personalised medicine: only 50% of people with chronic Hepatitis C Virus infection will respond to interferon-α therapy, and it costs €12,000+ a year, so we'd dearly like to know who will respond: not least because the side-effects of interferon are almost as bad as the disease.  Now we are clearly talking about personalised intestinal bacteria.  There are people out there, whom I've never met who have something in common: they have essentially the same bugs as me and therefore the same pitch of glucose intolerance, possibly similar food preferences, the same sort of winter sniffles.

As this intestinal flora changes radically and within a couple of days when we have a change in diet, it is not beyond belief that the bugs inside are telling us what to eat. That, frankly, seems a little invasive.

Multitudes down there

I have finished Ed Yong's I Contain Multitudes, his book about the intestinal microbial flora. It's gallop and has a number of interesting stories about how unexpectedly nifty are the interactions that have been driven into nature by evolution. For many of us in Europe, such stories negate the idea of a deity.  Darwin and many others have objected to the cruelty: I cannot persuade myself that a beneficent and omnipotent God would have designedly created parasitic wasps with the express intention of their feeding within the living bodies of Caterpillars. But for me it's the complexity: surely if Your Omnipotence wanted to creates something nifty from scratch you'd be a bit more streamlined and efficient.

Dr Yong's thesis is that "the world we see is profoundly influenced by the world we can't see". My Food & Ferm microbiologists can see microbes, because they can do a Gram stain and use a microscope. But not all microbes; because the vast majority won't grow happily, or at all, on a Petri dish in a laboratory incubator. In one of our series of experiments, I brought in a jar full of soil and they isolated different bacteria fom the jar but we had no confidence that the colonies of dividing cells observed a couple of days later were major players in the ecosystem of that spoonful of soil.

As a modern multimedia publisher, Yong wrote a book but teamed up with a film company TangleBank Studios to make a series of <wow> short films based on the book. I don't know about you but I'm spoiled for reading my the presence of youtube which is effortless in its digestibility. It took me weeks of snatched snippets and rare whole chapters to plough though the book: my brain fighting for consciousness with the requirements to process dinner. Talking of dinner, I Contain Multitudes, is pretty comprehensive in its rejection of oral probiotics as aids to a healthy gut and hence to health & happiness. It is more or less inconceivable that pot or two of Actimel containing a single [purity ensured to get licenced] strain of a single species of Lactobacillus is going to be able, on its own, to do enough. On the other hand a far more complex mix is used in FMT as effective treatment for Clostridium difficile aka Cdiff. But that is definitely not reproducible from treatment to treatment and is administered per anum. No sane person is going to try a fecal microbial transplant by mouth: leave that to dogs . . . and indeed to rabbits.

It is more elegant to eat bacteria-food than bacteria themselves. Most living bacteria get blitzed by the concentrated hydrochloric acid in the stomach but complex sugars can come through intact. This is one of the peculiarities of breast-milk. There are a bunch of indigestible sugars secreted into the milk that do no direct good to the nursing infant but seem to tilt the balance of power in the intestinal flora; giving a bit of a leg-up to some species, so that they can more effectively exclude the black hats.
https://www.metafilter.com/161203/Breast-Feeding-the-Microbiome

If we're talking about babies we're talking about birth. Yong went to NYU and innerviewed Maria Gloria Dominguez-Bello: the Go-To for thoughts about what she calls vaginal yoghurt and its importance in establishing a functional microbiome in a newborn when s/he is delivered. It is called labour for good reason because a lot of work is going on down there to extrude an enormous 'uman 'ead (and the smaller trailing tadpole of shoulders and feeble diminutive legs) through a smaller hole in the pelvic floor. All that oxytocin squeeeze forces the yoghurt . . . good bacteria . . . vaginal microbial community into every orifice, fold and crevice of the baby's body. There are definite and reproducible differences in the gut flora of kids delivered vaginally or by C-section but these diffs regress to the mean over the next sveral weeks. The jury is out on whether there are long-term effects on the health {obesity? diabetes? asthma?) of the two cohorts.
Too much in Ed Yong's book to cover here. Get it out of the library - I did.

We all got guts

Wexford Science Café WSC met, as ever, on the 3rd Tuesday [15th] of October 2019 in the Sky&Ground. It was me, again [*], talking about the gut and its darkling denizens. This has been of spectator's interest to me for at least a decade and is more recently surfacing into public discourse both scientific and popular-press. Needless to say, a lot of unsubstantiated nonsense is uttered in the latter medium. The field is at the stage now where a lot of data is accumulating that changes in the gut microbiota are associated with irritable bowel syndrome IBS; inflammatory bowel disease [worse!] IBD: Crohn's Disease CD, ulcerative colitis UC; peptic ulcer [Helicobacter prev]; obesity; diabetes. No surprises there; although it is not obvious what is the cause and what the effect of these co-occurences. What might be more surprising are the psychobiotic associations between the gut flora and . . . anxiety, autism, chronic fatigue, dementia, depression, Parkinson's. And note that your gut flora goes on a journey from cradle to dotage with different classes of microbes rising and falling in a reasonably predictable manner as we age.

Sources: nobody expects you, dear reader, to get down and dirty with the scientific literature. Each paper will normally present only one study indicating that bacterial strain X is associated with condition Y in either mice or humans, occasionally both. If you take the materials and methods on trust [and you shouldn't!], you can get the key factlet from the PubMed abstract. Or you can read Giulia Enders book: Gut: The Inside Story of Our Body's Most Underrated Organ; [originally Darm mit Charme. Alles über ein unterschätztes Organ] which I reviewed a tuthree weeks ago. I was all set to present an ExecSummary of that book when one of the WexSciCaf lurkers pointed me at The Psychobiotic Revolution by Anderson, Cryan and Dinan. Scott Anderson is a US-based science journalist, while John Cryan and Ted Dinan are academics from UCC in the Independent Republic of Cork.

In the airy arm-wavy world of popular science books you have to polish your crap-detector before you invest time and money in 'facts' therein presented. Here, I'll share some of the interesting intel which I gleaned from my reading.

The money is in probiotics but you and I don't want to spend our hard-earned dollars on products of dubious efficacy and doubtful quality control. Dinan & Cryan cite one study where the contents of 13 probiotic supplements were compared to what it said on the tin. Only 4/13 had a table of contents than actually matched the contents. Probiotics are food supplements and have a far lower administrative and licencing bar to leap than drugs which are classified as medicine. But the thrify should follow the prebiotics route: these are the dietary changes that can encourage the growth of good bacteria: try ginger, garlic, carrots, apples for starters. Actually, keep it simple and follow Michael Pollan [multiprev]: Eat food; not too much; mostly plants. Un-food is anything that comes in a packet with more than 6 indredients.

There has been a bit of interest recently in the few cases of auto-brewery syndrome. This occurs when a colony of bakers' yeast Saccharomyces cerevisiae, against the odds and its normal environment, sets up shop in some person's intestine. There it scarfs up any passing sugar and anaerobically converts it to ethanol and carbon dioxide. The CO₂ causes a certain increase in fartiness but the alcohol crosses the intestinal epithelium and starts to intoxicate. I don't think you'd have a leg to stand on [you'd be legless, arf arf] in court if you got arrested for driving under the influence.

Now before I forget, I'll note some of the major players in the gut flora: some good and some bad; all just tryimng to make a living. There may be 1,000 different species of microbe donw in the dark, but 99% of them fit into 4 different Phyla [major groups of bacteria]

• Actinobacteria
• Bifidobacterium longum, B. breve; B. dentium [richer in infant guts]
• Proprionobacterium shermanii [bubbles in Emmenthal]
• Firmicutes
• Clostridium difficile, C. botulinum [botox]
• Bacillus cereus [re-heated rice poisoning]
• Lactobacillus spp. LABs good guys
• Bacteroidetes
• Bacteroides thetaiotaomicron [prev]; B. fragilis; B. plebeus [freq in Japan]
• Prevotella
• Proteobacteria
• alpha: Rickettsia prowazekii; Brucella abortus [prev Alice Evans]
• beta: Neisseria gonorrhoeae, [the clap] N. meningitidis [meningitis]
• gamma: Escherichia coli and other enterics incl Salmonella; Pseudomonas aerogenosa
• epsilon: Campylobacter jejuni [food poisoning] Helicobacter pylori [ulcers]

[*] Footnote: Wexford Science Café is still trundling along - but seemingly only if  I continue to push and heave t'bugger up hill. It just doesn't seem to be gathering momentum although further adherents occasionally appear. As with a lot of such voluntary things, 90% of the work is done by 10% of the people. As a max of ten people turn up on a good day, the 10% is Me. When the call for next month's speaker is issued, everyone looks at their feet. And nobody seems willing to take on the minute adminstrative burden of calling the faithful to prayer once a month [Over the Summer, I e-asked this question direct of several of our most frequent attenders, only some of whom bothered to reply and all of whom were too busy]

Clostridium damned difficult

Clostridium difficile was being written up again last week in Nature.  It's an awkward sort of a microbe: difficult to diagnose, difficult to culture in the lab, and a serious killer to boot.  Ordinary folk don't even know how to pronounce the specific name:  a ploddy diffiseel ? a pedantically sounded final e diffisilé ? a florid italinate diffeechilley?  Most of us, including wikipedia, give up and call it C-diff.  It's interesting because it is somewhat opposite to Marshall and Warren's H.pylori, which can be cleared up pretty damned quick with a short course of antibiotics.  Gonorrhoea used to be similarly amenable to treatment until we squandered our augmentin on pigs and as growth promoters in chicken.

C-diff on the other hand usually springs up to kill after a short course of antibiotics has shifted the balance of power in the gut to allow this minor (<2%) player in our intestinal flora to foment its revolutionary take-over.  C-diff is indicated by a watery diarrhoea with a distinctive odour, fever, and a recent course in antibiotics. It is a classic iatrogenic (doctor induced) nosocomial (hospital acquired) infection, far more common in places for healthcare than in the outside world and often induced by medications which suppress acid production in the stomach (hello Tagamet). It makes you think that having a gastric pH not far off that of car-battery acid might not be primarily about digesting food but rather for digesting pathogens before they get access to the goodies further down the tube.  And once you've got C-diff in spades, it's really hard to shake off because it is resistant to so many of the antibiotics - that's presumably why it is triggered by a course of these drugs administered for something else.

In teaching Food and Fermentation Microbiology this last year (great fun!!), I've tried to encourage the students to use their noses, which can be pretty accurate diagnosticians.  You know how domestic trash has a really distinctive smell which is different from toilets which is different from pig-slurry. After 5 days without a fridge during the last power-cut, my sour-dough starter developed a worrying smell of acetone with overtones of esters (pineapple, pear-drops, hint of jasmine to a better nose than mine).  It was still full of oomph for raising bread but the product was very sour.  So I'm still dithering about throwing it out and getting fresh start from a neighbour.  Needless to say (the young of today - harrrumph) the students refused to engage and skittered about the room squeaking girlishly holding their noses - some literally.  I'm sorry to use "girlishly" but you know what I mean and the boys were worse than the women.

But as with so much in our scientific world there is a three-letter acronym (TLA) in the wings which is showing great promise for forcing Cthulhu-diff back into the cellar and shutting the trap-door on it: not to wipe it out entirely but to allow the other denizens of the dark to keep it under control.  FMT is faecal microbiota transplantion and it works on the old principal "Eat shit, a trillion horse flies can't be wrong".  Of course, science tries to make it more sciencey than that and to make it more uniform and reliable but the idea is to deliver an aliquot of microbes from a healthy gut into the intestine which is infested with C-diff: by nasal tube or from the other end by enema or colonoscope.  This is rather humbling: the intestinal flora is comprised of about 200 trillion cells from maybe 10,000 different species, and we have less idea about how they function and interact than we do about the animals than cavort and copulate and kill on the plains of the Serengeti.  Despite not knowing how it works, we now cannot deny that work it does. A year ago the first randomised controlled trial of this therapy was wrapped up early because those receiving FMT were twice as likely to have their symptoms resolved and it was deemed unethical to continue giving the crappy no-crap option when the crap option was clearly better.

The FDA is now scrabbling to get its regulatory act together to allow this therapy before C-diff kills its annual quota of 14,000 US citizens and a pro-rata equivalent of Europeans.  BUT we don't want to repeat the errors of the Blood Transfusion Board which developed and delivered a new therapy for hemophilia which, because it was badly thought through, contrived to infect 300 misfortunate bleeders with HIV.  So regulation is probably a Good Thing if only because it might "reduce the demand for risky at-home procedures" (!?).  Also because we know so little about how the human intestinal flora works, we want to be careful that we don't leap from the C-diff frying pan into the, as yet unknown/unnamed, C-death fire.  The whole story is freely available at Nature.

Great God Mullein

Great Mullein | Coinnle Muire | Verbascum thapsus is [triffid alert] an arresting part of the Ireland's native flora. Up to 2m tall with pale greyn furry leaves as big as a Sasquatch boot-sole and distinctive upstanding reproductive parts. Sometime last year, one of our slightly-woo friends dug up a specimen up and gave it to The Beloved. It was deposited in a packing crate [because it came with a large ragged clot of top-soil] in a corner of the polytunnel and more or less forgotten. Occasionally over the last 12 months, I've dumped a bucket of water into the crate and most if it has run straight through to make a temporary downhill puddle.

But in mid-May, I discovered some poppies Cailleach dhearg Papaver rhoeas struggling in the same adverse xerophytic desert corner of the tunnel. Poppies are the best of weeds, growing in most unlikely places and producing culinary seed - I like poppies. I started clearing around the poppies until The Beloved stopped me with "Whoa, sunshine, that's my mullein you're messing with". So I stopped hacking at the leaves and we carried the crate outside. Later the great mullein (just beginning to show yellow flower) was re-installed with honour in our largest blue-glazed earthenware planter on the recently de-thatched patio in front of the house. Now that I can reach my log-table without getting wet socks, I am resolved to sit out beside the mighty mullein with my morning quart of tea.

Botanical Society of Britain and Ireland BSBI publishes distribution maps of most-all of the plants found on these islands: herrrre's Mullein [map L] the darker the square, the more recently that species has been observed in that 10x10 km location. The Sunny South East seems to be the epicentre of V. thapsus's plan to take over the island and reduce mere people to Those Who Serve Mullein. But that recent activity may be all down to the indefatigable Paul Green populating his Flora of County Wexford [bloboprev]. 

The medical take seems to be that mullein is mostly harmless. If you choose to extract the active principles [saponins, polyphenols] from the leaves by steeping them in hot or cold oil, then you're not going to kill anyone. But you're unlikely to cure asthma bronchitis congestion dropsy eczema frostbite gout . . . either. Part of the problem is that there are 250 species in the Genus Verbascum and folk-practitioners may be using them inter-changeably. Some known anti-inflammatory and anti-microbial compounds have been isolated from some of these species. Maybe it will be as effective for me to commune with the The Mullein (while having tea, like) to spare my life when they uproot and take over the world.

God? Verbascum blattaria moth mullein seems to be immortal. The Beal weed-seed longevity project 1879-2100 is still going.  2021 Seedlings upcommmming.