May 2015


Gut feelings

By Jo Chandler
Gut feelings

A scanning electron microscope image of Campylobacter jejuni, a species of bacteria commonly found in animal faeces. Image by De Wood and Chris Pooley, US Department of Agriculture

The mysteries of the microbiome

The tapas was a mistake. Or maybe the wine that washed it down?

Suffice to say that come morning, at the business end of a flying trip to Brisbane, I’m a bit embarrassed about my specimen. But I’m on a deadline. Done is better than perfect.

I wave a pair of long swabs about the clench of toilet paper as per the crisp instructions folded into the collection kit. (“Quality, not quantity,” the subtext pleads.) Slide them into the test tube, seal it and swaddle it in tissues. Deposit the job into a postage-paid padded envelope and drop it deep into my handbag.

The plan was to deliver it personally to a University of Queensland laboratory, home to the fledgling Australian Gut Project, where I had presented myself the previous afternoon with dual credentials – journalist and lab rat. (For reasons we shall return to, my entrails are uncommonly interesting.) I’d hoped to observe as my sample was fed into the “poo-bot” for processing. But bravado has failed at the prospect of my contribution to science being critiqued by double-gloved faecal connoisseurs who can’t quite meet my gaze. A post box will do nicely.

Rachel Carson once observed that “in every grain of sand there is a story of the earth”. As a biologist, she might also have recognised that in every shit there is the story of a life. But given what science has learnt in just the past decade, this would be a grievously short-sighted and anthropocentric view: our guts harbour tens of trillions of microbial lives entwined with our own, and with the ancestral human narrative.

Their collective story is so intimately exposing, little wonder we might hesitate to dwell on it, let alone share it. Yet the torrent of medical literature compels us. Journalists at the New York Times and the Guardian delve deep into their own poo to explain the unfolding science. To borrow the title of a recent public lecture at the University of Sydney, ‘The Importance of Talking Shit’ is beyond question.

So if you have not yet had the pleasure, let me introduce your microbiome. This is the genetic entirety of the invisible bespoke ecosystem of your microbiota – bacteria, viruses, archaea, eukaryotes and fungi.

They roam your skin, foment in every ripe crevice: vagina, mouth, armpits. But their main habitat is the gastrointestinal tract, home to 95% of your microbial community, some 1000 species. They work the boundaries of your external world and your human genes. They power and instruct the machinery of your body, process food, educate and fire the immune system, battle malicious invaders, build tissue, and communicate with the brain and lymphatic systems.

For the longest time this invisible realm has been unexplored; the vast majority of its life forms evaded all attempts to capture and culture them in the laboratory. Now science is launching the microbiological equivalent of the Apollo missions up what my father likes to call the Khyber Pass.

We’ve had the US$180 million National Institutes of Health Human Microbiome Project (HMP) and the €22.2 million European equivalent, MetaHIT (Metagenomics of the Human Intestinal Tract). Gut analysis projects under way in San Diego, London and now Brisbane enlist next-generation genetic sequencing technology and stool samples from across the globe.

For a small fee, individuals can obtain readings of their faecal biota and contribute to the emerging census of the planet’s dominant living populations. We measure and compare our Actinobacteria and Proteobacteria; we learn that fat Americans have more Firmicutes and fewer Bacteroidetes than thin ones; that children in a village in Burkina Faso have whole communities in their gut that are not found in children living in Florence; and that while the DNA of every human is 99.99% identical, as little as 10% of our gut microbes may be similar.

But the ambitions of microbiologists and the medicos drawn into their orbit are much grander than plotting this shit storm. Just as Louis Pasteur and Robert Koch harnessed germ theory 150 years ago to begin identifying, preventing and treating acute disease-causing bugs, today’s researchers investigate the potential of manipulating our microscopic fellow-travellers to tackle chronic diseases and some cancers.

Their hypothesis is that our microbial populations could play as powerful a role as genetics, lifestyle and environment in determining health. In developed societies, where the incidence of a clutch of chronic and so-called lifestyle diseases has risen as the threat of infectious disease has retreated, disturbances in the relationship between our external and microbial worlds have emerged as prime suspects in explaining rates of inflammatory bowel disease, colorectal cancer, allergies, asthma, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, metabolic syndrome and obesity.

There’s also intense scrutiny of the “brain–gut axis”, the interplay of bugs in the gastrointestinal tract with the central nervous system, and how it might influence neurobiology and conditions like Alzheimer’s, Parkinson’s, autism, depression, schizophrenia and anxiety.

All this depends on deeper scientific penetration of the microbial biosphere. The genetic material of the bacteria we carry in and on our bodies outnumbers our human genes by a humbling factor of at least 200 to one. And for every bacterium there are ten viruses. We are not ourselves.

We are, rather, “a seething ecosystem that has to be kept in balance and fed and maintained”, says Alan Cooper, director of the Australian Centre for Ancient DNA at the University of Adelaide. His breakthrough analysis of calcified bacteria plucked from the teeth of our ancestors has exposed the deep history of humanity’s shifting microbial inheritance. “We’re wandering around with this massive ecosystem which is influencing our mood, our diet, our immune response, our behaviour.”

These bugs relate the human story over generations, as Cooper’s work revealed. He discovered upheavals in populations of human mouth bacteria 10,000 years ago, when we started farming, and then again 150 years ago, with the industrial revolution.

In the span of our own lifetimes, microbial baggage records the pets we’ve owned, the partner we’ve chosen, the diseases we’ve caught. Most influential are the bugs encountered in our earliest months – from the floors we crawled, the milk we suckled, even the way we were delivered into the world. Babies born by caesarean section miss out on microbes normally acquired en route down the birth canal.

Our understanding of the influence of this history on our health and character is exploding. In 2004, fewer than 200 papers mentioning the microbiome were published in science journals; in 2014 the number nudged 4500.

The caveat is that much of the research is still in the exploratory phase. The picture emerging is of a deeply complex discourse of microbes, human genes, lifestyle and environment. Experts caution against hopes of off-the-rack therapies in the near future.

Nevertheless, “I think ten or 15 years from now, when you get sick, one of the first things the doctor will be measuring is your microbiome,” says Alan Cooper.

“Western medicine has ignored it for a thousand years,” he says, but now the rush is on. His laboratory has had approaches from more than a dozen medical teams in the past year who wanted help learning how to collect, measure and manage human microbial data. “I’m a disciple,” Cooper admits. “But it is going to be huge.”

In biologist Ernst Haeckel’s classic 1866 monograph depicting the tree of life, bacteria are tucked down the bottom as “Moneres”. By the 1990s phylogenetic analysis had evolved to position multi-cellular organisms (including humans) at the margins, overshadowed and vastly outnumbered by other Eukarya, Archaea and Bacteria.

Phil Hugenholtz, director of the Australian Centre for Ecogenomics at the University of Queensland – and overseer of the laboratory that will analyse my poo – is a modest type with a grand ambition. He wants to reconfigure the tree of life again, to fully recognise the dominance and diversity of microbes. This would “do for biology what completing the periodic table did for chemistry”.

The technological tools are close enough to dare to imagine it as a quest for our times, though the scale is terrifying. Microbes have been around for 4 billion years, which gives them a 3.5-billion-year head start on multicellular organisms. Most are still characterised as microbial dark matter. It’s Hugenholtz who likens the search for them to deep space exploration. These life forms are apparent in the vortex only by virtue of the noise pulsing from their sequenced DNA.

Hugenholtz opens a file on his computer and sends the cursor rappelling down pages of G–A–T–C code, the base script in which DNA is written, spelling out the genetic evidence of millions of unidentified creatures. This is the black hole into which his crew will boldly go.

That our environment harbours teeming populations of teeny life forms is not news. As the English polymath Robert Hooke wrote in Micrographia, his watershed foray into the invisible world, in 1665:

By the means of Telescopes, there is nothing so far distant but may be represented to our view; and by the help of Microscopes, there is nothing so small as to escape our inquiry; hence there is a new visible World discovered to the understanding.

The creatures sharing our bodies were exposed in 1683 when a Dutch amateur scientist scraped some gunk from his teeth and examined it under lenses he made with such precision they could magnify the view 200 times. Antonie van Leeuwenhoek observed “with great wonder … many very little living animalcules, very prettily a-moving”. These are credited among the first observations of living bacteria.

The reason these “animalcules” are again exciting interest is that we stand at a similarly transformative moment, explains Hugenholtz. “It’s like where physics was in the 1950s. It’s just going crazy.”

Genetic sequencing technology and the evolving systems of wrangling the information it yields – bioinformatics – have come of age together to deliver scientists a step-change in apparatus equivalent to the advent of the microscope or the telescope.

“For most of the history of microbiology, if we wanted to know about a bug we had to grow it in a Petri dish. But it turns out that only a very small number of microbial species can pull that trick off,” says Hugenholtz. “We all know about E. coli [Escherichia coli] because we can grow it on a plate. But E. coli in your gut is an absolute bit player.” It gained notoriety by virtue of being among the mere 1% of microbes that scientists had been able to culture in the 300 years after van Leeuwenhoek’s discovery.

Without cultured bugs, microbiologists couldn’t crack open the genetic information to determine what they were dealing with. Even if they could see something under a microscope, was it new? How did it relate to other organisms? Where did it sit in the tree of life?

Then one day in the early 1980s, Norm Pace, a Colorado microbiologist trying to culture specimens out of the Yellowstone hot springs, “was so frustrated that he thought, What if I just throw them in a bucket of phenol to get the DNA out?” says Hugenholtz. By mixing pond scum with phenol and spinning it in a centrifuge, he could purify and extract DNA without having to grow cultures.

Within ten years the process was streamlined and samples were routinely distilled to their DNA and RNA by feeding them through a machine that works as a sort of molecular photocopier (a polymerase chain reaction, or PCR, machine), yielding millions of copies, enough material to plunder for genetic information.

Bypassing the Petri dish put the microbiological world up for grabs. Scientists could scoop up samples from anywhere – swabs from a mouth or fungi from a tree or vials from the deep ocean – analyse whole communities and discover new species.

“There was this huge amount of diversity out there that we’d been completely ignorant of,” says Hugenholtz, who found himself in the thick of it as a postdoctoral researcher in Pace’s laboratory. “It’s like we have this telescope, and it’s only 20 years old, and it’s increasing its resolution.”

It started by scanning the bugs for one marker gene – 16S rRNA – a short genetic barcode shared by almost all life forms (in eukaryotes it’s the slightly larger 18S). This serves as the microbial gold standard for distinguishing one organism from another, or building a profile of all the characters in a community.

Then the technology progressed to metagenomics, collecting all the genes of all the members of a sampled community. “In addition to telling who is there [bacterially speaking], you can tell what they are capable of doing,” says Hugenholtz.

“We look at humans, mice, termites, plants, marine samples, sludge – basically any ecosystem that you can extract DNA out of. In some ways humans are a little bit on the dull side. We don’t have the diversity of, say, a deep sea sediment.”

Dull, and profoundly self-interested. The interconnection between the human genome (the entire book of our genetic instructions) and the microbial genome quickly became ripe for exploration and discovery.

For instance, comparisons of laboratory-bred germ-free mice (without micro-organisms) and regular mice, and obese and lean mice, revealed the role of gut microbiota in regulating fat storage and metabolism. Differences in the relative abundance of two major bacterial groups – the Bacteroidetes and the Firmicutes – emerged as key influencers. If germ-free mice were colonised with the poo of obese mice, they got fat, while those dosed with the gut community of lean mice stayed lean.

A similar experiment found that gut bacteria influenced the brain chemistry of mice, making them calm or anxious.

Inevitably, it’s complicated. Microbes matter, as do the host’s genes, environment, diet and lifestyle. But the potent role of previously neglected bacteria in the mix has energised relationships between microbiologists, medical researchers and clinicians.

Phil Hugenholtz’s laboratory is working with various teams investigating the microbial ecology associated with conditions ranging from urinary tract infections to chronic and acute respiratory conditions and diseases including cystic fibrosis, pulmonary fibrosis and sinusitis.

It has recently collaborated with a team at the University of Newcastle looking at how cigarette smoking can alter gut bacteria, and which is experimenting with “transpoosions” of faeces from mice with emphysema into healthy mice and vice versa.

“The ‘smoked’ mice, if you exposed them to the healthy poo, would improve, lose some of the lung disease,” says Hugenholtz. “What that is telling you is that the gut bacteria are involved in some of the symptoms. That makes sense, because the gut is like the focal point of conversation between us and our microbiome … It can have systemic effects.”

The findings – soon to be published – are poised to excite substantial interest because the experiment is shaping up as the first to link activity in the gut microbiota to disease elsewhere in the body.

In another project, the laboratory is analysing microbes from the skin rather than the gut. The research is led by Ian Frazer, co-creator of the HPV cervical cancer vaccine (and former Australian of the Year), and investigates whether skin microbes have a role in switching on squamous cell carcinoma.

“It makes some sense in helping us understand why, for example, diseases which obviously have some genetic component don’t appear in everyone who has the right genes, and don’t appear straight away when you are born. It all depends on when you encounter the bugs [those genes] can’t deal with.” It is, Frazer says, “a whole new way of thinking about the causes of disease”.

Frazer’s findings – also pending publication – build on the work of a Swedish team showing a strong association between a particular bug and skin cancers.

Hugenholtz has also set up the Australian Gut Project in association with Rob Knight, the New Zealand–born scientist who initiated the American Gut Project and is a dynamic force in the research. “I bumped into him once in an airport in the US and he had a thermos flask,” Hugenholtz recalls. “I asked, ‘What’s in there?’ And he said, ‘Diarrhoea – I got a bad case of the squirts in Mexico, so I’ve been tracking it.’”

It was Knight’s team who found that babies delivered by C-section had a different ecosystem of bacteria to those born vaginally, and who wondered whether this might be linked to higher rates of allergies, asthma and some infections. When his own daughter was born by emergency caesarean, Knight and his wife “took matters into our own hands”, as he explained in a TED talk, and “made sure she was coated with all those vaginal microbes that she would have gotten naturally”. A long-term health study of a cohort of newborns similarly handled is now under way in Puerto Rico.

Meanwhile, Knight has kept a close eye on his daughter’s microbiota and that of a colleague’s baby. Their nappies were routinely sampled, and the creatures found therein will likely be worming their way into medical literature for years to come.

The first two years of life are crucial in shaping a mature microbiome. We now know that the good stuff in breast milk includes ingredients that nourish a newborn’s gut bacteria, and it is recognised as defining for lifelong health. Multiple studies have demonstrated that early exposure to pets or siblings gives protection against allergies. And the use of antibiotics in children under two is being closely examined, with evidence emerging of links to obesity.

Alongside rising awareness of the microbes that safeguard health comes increasing scrutiny of the use and overuse of antibiotics to kill off those that are a threat, and concern about the antibiotics that are so prevalent in farming and food production. These conspire to create the evolving biological “tragedy of the commons” of antibiotic-resistant infections.

Using antibiotics to treat disease is akin to napalming a jungle to kill a tiger, says Hugenholtz. With some tigers there’s little alternative, though doctors and individuals should be judicious. The indications are that in otherwise healthy adults the microbial community is resilient and will usually bounce back after an antibiotic assault, but there are increasing questions, particularly about the effects on young children.

What’s clear, says Hugenholtz, is that it is important to “let nature calibrate your immune system, through your microbiome, so that it knows how to react in a sensible way” when it comes across something unfamiliar. Otherwise you can get a hyper-immune response, inflammation being the classic one.

This mechanism underwrites the “hygiene hypothesis” for rising rates of autoimmune and allergic diseases in Western societies, the idea that we have so sanitised our world that our defences have grown weak. In a validation of old wives and the five-second rule, it turns out that a little dirt never did hurt anyone.

Now, at the risk of vanishing up my own bottom, I’d like to talk about my microbiome. Trust me, it’s instructive.

On an assignment investigating Papua New Guinea’s tuberculosis epidemic a couple of years ago, I got too close to the story. A little Mycobacterium tuberculosis stowed away in the lining around my right lung, eventually emerging as multi-drug resistant (MDR) TB.

I was treated with a dozen antibiotics over 18 months – some very potent, some via intravenous drip, most in tablets by the handful. That’s a lot of napalm, but then it’s a bastard of a tiger. Each year, around 500,000 people develop MDR TB, and just one in ten are – as I was – identified and successfully treated. The emergency is shaping up as a scourge experts characterise as ebola in slow motion.

My gut endured a nuclear winter. Six months on, what survived? I’m curious to find out what clues my poo contains about how things are going up there. So are some of the experts I overshare with. The effects of antibiotics on gut microbiota, and how those microbiota respond to medicine’s arsenal in the context of rising rates of antibiotic-resistant disease, are urgent areas of investigation.

It turns out that sifting microbes out of shit is a bit like panning for gold. You may find tantalising glimpses, but the mother lode is hidden somewhere upstream. As microbiologist Mark Morrison at the University of Queensland counsels, in a remark that could only be delivered straight by a person with 30-something years of gastric investigation in their CV, “there’s a lot of noise around stool samples”. (He’s talking in research terms.)

Faecal profiles give an indication of whether some communities might be out of whack. They might suggest that you cut down on protein if your Firmicutes are too dominant, or eat more whole grains to encourage Prevotella. But the heavy-duty action occurs deep inside, along the difficult-to-access mucosal lining of the gut.

Morrison is part of a team developing a prototype technology that will, via endoscope to avoid faecal contamination, collect biopsy samples from the gut wall, allowing uncontaminated investigation of the microbiome’s ground zero. (I don’t, dear reader, volunteer for this one.)

The hope is that this technology will provide some insight into the ubiquitous tummy aches and gastric gripes that account for one quarter of GP consultations, and almost half of all specialist consultations. Most of these remain undiagnosed.

But there is also a huge amount to do to untangle cause and consequence when a particular microbial profile is identified in relation to a particular condition. “We are still very much in the data acquisition and association phase,” says Morrison.

He reflects that it is only 30 years since Western Australian researchers Barry Marshall and J Robin Warren published a watershed finding that linked a bacterium they discovered in the gut of patients, Helicobacter pylori, with peptic ulcers and gastroenteritis. Marshall took drastic steps to prove the bug as cause rather than effect by swallowing a mouthful of the bacteria and developing acute gastritis. The duo endured “the full seven stages of scientific disbelief”, says Morrison, before eventually being recognised in 2005 with a Nobel Prize.

There are now less dangerous ways for scientists to examine microbial communities in a holistic and mechanistic way. Morrison is working at the front line of that effort in collaboration with gastroenterologist Gerald Holtmann under the auspices of Brisbane’s Translational Research Institute (TRI), co-founded by Ian Frazer.

I meet the pair in TRI’s lush tropical atrium. Stacked high around us are glass-walled laboratories. White-coated researchers circle about like fish in a bowl. Holtmann, a German of gracious manners, politely declines to shake hands as he has had flu and is still suspicious of his own microbes. He is in no doubt of the power of the unseen.

“I would expect a complete paradigm shift in many fields based on this knowledge,” he says. “I am very confident that many book chapters have to be rewritten due to the microbiology technology that has become available.”

He and Morrison are working on projects investigating microbial triggers and therapies for increasingly common gastrointestinal complaints such as Crohn’s disease and functional dyspepsia (reflux, upset stomach).

The villain of the peptic ulcer story, H. pylori, is a particular focus. Holtmann is investigating it as a suspect in Crohn’s, “which has gone up like crazy”, but in this scenario his working theory is that the absence of the bug might be the problem.

In societies with a lot of H. pylori there is a very low incidence of Crohn’s, whereas in “clean” countries like Australia its prevalence is high. It’s a kind of hygiene barometer – if H. pylori is missing, chances are that the broad spectrum of exposure to a variety of bugs has been narrowed.

Holtmann’s particular passion is neurogastroenterology – the brain–gut connection. All those patients going to the doctor with symptoms like fullness, abdominal pain, nausea and indigestion “are also frequently fatigued, prone to be depressed and anxious”.

“You could argue – is it just a psychosomatic condition?” Holtmann says. “Now the hypothesis is that the gut inflammation is not simply driving a disordered function in the gut, like indigestion, but that this inflammation is systemic with implications for our brain function.”

“My belief,” he continues, “is that very specific interaction between the person-specific mucosal microbiome and the immune system is the determinant for a lot of disease conditions.”

Inflammation has long been a suspect in the pathogenesis of cancer. Hence interest in the microbiome extends from debilitating to potentially deadly disease.

“The body is pissed off. It’s constantly having to put out bacterial-caused fires, which seems to be a key component of cancers and other irritations,” says Alan Cooper, the evolutionary specialist from the University of Adelaide. His work explaining that it hasn’t always been thus is one of the insights exciting medical researchers.

He’s discovered, for instance, that our ancestors had magnificent teeth and gums, and that the dental pathogens that thrive in modern mouths exploit tooth and gum disease to enter the bloodstream. “This is a whole new route of infection we never had before.

“All through our co-evolution we’ve had these mutually beneficial relationships, everything sorted out over millions of years. Bacteria are important in so many ways. Then we change the relationship by completely changing our diet and lifestyle.”

Almost three weeks after I pop my sample in the post, it is returned in the form of an emailed spreadsheet with 180 lines of Gs, Cs, As and Ts and a cast list of the identifiable bacteria residing in my gut. It’s a scary line-up.

Other journalists who have gone down this route smugly share report cards of enviable bacterial biodiversity, brandishing their Prevotella and Roseburia as testimony to their healthy diets and free-range lives. But my shit is full of shit.

TB treatment has clear-felled my gut. Microbial weeds inured to the antibiotic barrage have exploited opportunity in a denuded landscape, pushing out major populations like the Firmicutes. “You are indeed very atypical for a human,” observes Phil Hugenholtz. He wonders if I may have more in common with the kakapo, a critically endangered New Zealand parrot species that was also dosed up on antibiotics to try to secure its survival. Google reveals it as a nice enough little bird, yet it’s not a happy comparison.

Hence I have a visceral interest in the next chapter of this medical revolution, the one where we learn what a healthy microbiome looks like; the precise consequences of a compromised one; and what might be done to rehabilitate damaged microbial ecology.

Are there strategies to help me evict the feral opportunists and lure back friendly tribes? What is the potential for any of us to manipulate our bugs to improve our health?

In a recent publication by Nature and Scientific American, devoted to “innovation in the microbiome”, Stanford University microbiologist Justin L Sonnenburg forecasts that advances in synthetic biology mean that “in the not too distant future each of us will be able to colonise our gut with genetically modified ‘smart’ bacteria that detect and stamp out disease at the earliest possible moment”.

The stumbling block between here and there is the highly individual and complex nature of every microbiome. “It is not as simple as ‘push A and B happens’,” Hugenholtz cautions. “We’re at the beginning of this. These are complex relationships. You’ve got to think of your microbiome as a rainforest. It’s an ecosystem, a food web.”

Interfering in natural systems is a fraught business, a lesson never far from consciousness in Queensland. Remember when the cane toad seemed like a good answer to the cane beetle?

This is why Mark Morrison says that the next step forward for microbiology will require a step back – to the Petri dish, finding ways to cultivate biological specimens. In an anaerobic chamber in his laboratory at TRI he shows me plates dusted with samples of poo from the University of Newcastle’s smoked-mice experiment – trays and trays of painstaking attempts to spawn the suspect bacteria linked to emphysema.

“Genomics has empowered us in terms of providing an inventory of what the microbial dark matter is. [But] we don’t know what its genetic information is doing, what it is driving, how it responds to signals, what are the ramifications. Now the challenge for microbiologists like myself and Phil is to turn that genomic information into life.”

If microbial medicine is “going to go anywhere near achieving the panacea people are proposing, we need to understand a lot better the biology of the organisms and their interactions”.

Meanwhile, there’s a lot of chatter, educated and otherwise, about the use of faecal microbiota transplantation (FMT) to tackle a range of gastrointestinal and other conditions.

Stool from a healthy person is transferred into the colon of a sick person to recolonise the sick system with beneficial bacteria. Despite the yuck factor and the obvious perils of messing about with other people’s unscreened poo, there’s a thriving DIY movement in this area.

In medicine, faecal transplants are, so far, only accepted as therapy for relapsing cases of the deadly antibiotic resistant Clostridium difficile. The method has been spectacularly successful in beating this diabolical bug, which causes severe diarrhoea, particularly among hospital and aged-care patients, killing an estimated 29,000 people in the US in 2011.

But Morrison’s colleague Gerald Holtmann counsels that, as yet, the clinical data to evaluate FMT in other contexts does not exist. A recent trial on patients with ulcerative colitis identified no beneficial effects. “In spite of the enthusiasm, it is important to wait for proper data.”

There is some good data suggesting that patients prescribed antibiotics can benefit from dosing up in advance with probiotics (live cultures), he says. How useful probiotics are after the event is less clear, but I’m giving them a shot.

There’s also recognition that the microbiome can be changed by altering the diet to starve out unwanted bugs. A scan of the suggested dietary regime is enough to make most creatures give up the will to live. Still, it is more palatable than a poo transplant, and it’s unlikely to do any harm.

I have another idea, inspired by Alan Cooper’s work on how modern living has so diminished the spectrum of our microbiota. What if I went to one of those shrinking pockets of old Earth? Someplace where humans and microbes coexist mostly as they have through the ages? Roll around in the dirt, eat local, breathe deep. Maybe this time I could imbibe some friendly bugs.

If that fails, there might at least be a quid to be made. As Cooper has quipped, “someone should go out to the pygmy bushmen in Africa, or into the Amazon, and tell them to patent their shit”. There’s gold in that bacterial diversity.

Jo Chandler

Jo Chandler is a freelance journalist who writes on human rights, development, climate and science. She’s a senior lecturer at the University of Melbourne’s Centre for Advancing Journalism.


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