Trust your Microbiome (Gut)

The gut feelings of psychic “scatomancers” who studiously examined the color, shape, and buoyancy of poo to forecast well-being and life prospects were more reliable than palm-reading, tarot cards, and astrology. They had “data,” and now we have the microbiome.

Who would have guessed a few years ago that traffic passing through the colon destined for elimination could be dignified with the name “organ,” or fecal transplants become a state-of-the-art medical therapy, or a national stool bank opened at M.I.T.?

The fermentation services of gut microbes were taken for granted, like their brethren in the garden compost heap. But no more!  The microbiome has a larger role in health than the digestion of food, and might even fill mysterious voids in human psychology and behavior. Since it is now being mined by researchers funded by the NIH Human Microbiome Program, the US military, European governments, and Big Pharma, the microscopic living soul of poo is no longer derided as an odious subject. The W.C. has swung open for scientific limelight to shine inside.

Friends or foes?
Friends or foes?

The first rays were focused on gut microbes by Elie (Ilya) Metchnikoff who introduced the concept of probiotics over a century ago. He studied people in the Caucasus Mountains reputed to live longer than anywhere else (their claims now repudiated), attributing their luck to fermented yogurt for conquering the putrefying bacteria supposed to release poisons into the body. He thought an unhealthy diet promoted growth of malign microbes with pro-inflammatory (pro-aging) effects that could lead to cardiovascular and other diseases which curb our years. Yogurt was proclaimed an elixir of life.

But his radical idea wasn’t sustained until modern bacteriology and genomics revealed the microbiome world and endorsed therapeutic probiotics. A recent study found that probiotics extended longevity in mice, but more surely they restore and rebalance the gut’s microbiome after antibiotic treatment and various intestinal ailments. It is easy to imagine that patients will soon take capsules packed with beneficial bugs for Crohn’s disease and irritable bowel, although cartoonists may rue the day when this more discreet treatment replaces fecal transplants for C. diff. infections.

Wilder speculations about the impact of microbes in mental health and ability were made by one of Metchnikoff’s contemporaries. Robert T. Morris who helped to bring aseptic surgery to America, wrote in Microbes and Men (1915): “A man is only what his microbes make him … freedom of the will is subject to dictation by the microbe.” He dared to suggest that microbes affect human character, psychopathy, and even genius. Sounds exaggerated?

He was not the first to notice that some of the most creative people had poor health—Nietzsche, Schopenhauer, and you name the rest. We might imagine a melancholic George Orwell inspired to write stories during his last tuberculous years, but is it really plausible that microbes themselves or their products boost the highest and the meanest achievements of the human mind? Morris’s big idea was nebulous, but at least a nice contradiction of Hereditary Genius (1869, 1892) by Francis Galton, the man leading the charge to eugenics who thought that genius and psychopathy ran in families. Since they occur rather sporadically, it is not quite so ridiculous to wonder if microbes play a role, or at least in combination with certain genetic alleles. Besides, we know the rabies virus affects behavior– rage, fear, and hydrophobia—and cumulating evidence suggests that Lyme disease and infectious mononucleosis cause chronic fatigue and other neurological symptoms.

So why not the microbiome too, which consists mostly of bacteria that vastly outnumber cells in the body? A gathering breeze of data supports the idea.

Tiny viruses slip easily through the blood-brain barrier, but bacteria can assault the fortress indirectly via fatty acid metabolites or triggering inflammation and powerful cytokine molecules from the immune system. The data are still far from sure, but animal experiments and association studies offer tantalizing clues that the microbiome affects the brain.

Germ-free mice have subtle neuroanatomical differences compared to normal animals—less serotonin (linked with depression in humans) and myelination (affecting nerve conduction), and altered transmission at synapses. More compellingly, gut microbes transplanted from one strain of mouse to another change the behavior of the recipient to mirror the donor’s.

Human populations are much harder to study but, for example, when Walkerton was flooded in 2000 the Canadian town’s water supply was contaminated with E. coli and Campylobacter many of its residents developed irritable bowel syndrome, anxiety, and depression. The question remains—were their symptoms “purely psychological” (a non sequitur?), or were they caused by inflammation from the original infection? Persistent, low-grade effects are hard to expose, as we know from the controversy over “chronic Lyme disease,” although science will eventually get to the bottom of it.

The neuroscience community with its refined sensibilities isn’t accustomed to musing about stool stories, but we hear murmurs about a relationship between the microbiome and autism, anxiety, Alzheimer’s disease, and schizophrenia.  The prospect of research grants is bending ears.

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