This article was first published in聽
鈥淚t makes me sick to my stomach.鈥�
That鈥檚 the line I blurted out when asked by a reporter about the U.S. government鈥檚 assault on science. I hadn鈥檛 thought about the expression, it just came out automatically. Why? I hadn鈥檛 actually been sick to my stomach. Surely, I thought, there must be some foundation for this common utterance that links the mind and the gut. That needed delving into.
Around 400 BCE, Hippocrates reputedly asserted that 鈥渁ll disease begins in the gut.鈥� He had no evidence, just a gut feeling. This was echoed two millenniums later by English physician John Abernethy, who in his 1829 book The Abernethian Code of Health and Longevity traced not only bodily but mental disorders to 鈥済astric derangement.鈥� He maintained that the gut and the mind were linked via the nervous system and claimed that 鈥渓owness of spirits, restlessness, disordered sleep, weariness and fatigue鈥� were caused by 鈥渧itiated digestion.鈥�
Abernethy鈥檚 answer to the problem was that humans needed to eat simple, natural foods instead of 鈥渢he refined, unnatural and often adulterated foods being increasingly consumed in industrializing Britain.鈥� Quite prophetic, given that today the role of fibre as found in fruits, vegetables and grains is a hot topic in the blossoming research that focuses on the 鈥済ut-brain axis.鈥�
Hippocrates and Abernethy were on the right track, although of course they had no idea that the connection between the stomach and the rest of the body is forged by the trillions of bacteria that inhabit our digestive tract. As it turns out, these microbes are not just lethargic bystanders. They can crank out a host of 鈥減ostbiotics,鈥� compounds that can affect conditions ranging from obesity, depression and neurological disease to anxiety, stress and cancer.
Our first glance into the gut-brain connection came through a hole in a stomach. That historical stomach belonged to Alexis St. Martin, a Canadian trapper working for the American Fur Company in Michigan. In 1822, St. Martin was accidentally shot in the abdomen and was treated by U.S. army surgeon William Beaumont. The bullet wound healed, but not completely, leaving a hole, literally a window into his stomach.
Beaumont recognized that he had been presented with an opportunity to study digestion and convinced St. Martin to allow a series of experiments in which food would be inserted through the hole and then withdrawn along with the digestive juices that were at work. He showed that the juices contained hydrochloric acid, and that vegetables were digested more slowly than meat. He also noted that when St. Martin became angry and irritable, his rate of digestion was affected. Thoughts were indeed able to make one sick to the stomach.
How about the reverse, namely Abernethy鈥檚 notion that 鈥渓owness of spirits鈥� may be caused by 鈥済astric derangement鈥�? That view was revived in the early 2000s when DNA sequencing made possible the identification of bacteria in the gut and revealed associations between depression and the composition of the microbiome. That connection was further bolstered when rats that had received a transplant of fecal bacteria from depressed patients exhibited depressive-like behaviour.
Then along came a Dutch study in which thousands of participants donated fecal samples and filled out questionnaires that assessed mental status. Some bacterial strains, Eggerthella, for example, were found to be increased in people who showed symptoms of depression or anxiety, while others, like Sobdoligranulum, were found to be depleted.
A theory emerged that short-chain fatty acids such as butyrate, as well as the neurotransmitters serotonin, dopamine, glutamate and gamma-aminobutyric acid (GABA), all of which can be produced by gut bacteria, can somehow modulate brain activity. It was already known that such chemicals are produced in the brain and can certainly affect its workings. For example, low levels of GABA in the brain have been linked to depression and mood disorders, so the idea that certain bacteria in the gut that produce this chemical may be able to alleviate depression is an inviting one. However, so far the evidence suggests that GABA cannot cross the blood-brain barrier.
Well, maybe it doesn鈥檛 have to. There is another connection between the gut and the brain: the vagus nerve. Animal studies have shown that gut microbiota can indeed alter GABA activity in the brain through the vagus nerve. The prevailing idea is that this nerve has receptors for certain postbiotics and when they are stimulated, a message is sent to the brain to synthesize the same chemical that had activated the receptor.
In Japan, a whole industry has arisen based on this possibility. There are chocolates and all sorts of beverages that are fortified with GABA and claim to reduce anxiety and improve sleep. There is even a tomato that has been genetically engineered to have high levels of GABA with somewhat dubious claims of lowering blood pressure, relieving stress, improving sleep and protecting skin health by maintaining skin elasticity. For the latter, though, 5-7 high GABA tomatoes have to be eaten daily. Japanese researchers have even discovered that if tea leaves are stored for 10 hours in a nitrogen atmosphere, they accumulate a large dose of GABA that at least in rats is able to lower blood pressure. Along with GABA-enriched tea, the internet offers a host of GABA dietary supplements. Maybe they work, maybe they don鈥檛. No evidence of efficacy is provided.
Even more alluring than the possible influence of gut bacteria on the brain is their potential to improve the response to immunotherapy, a cancer treatment that enhances the ability of the body鈥檚 immune cells to seek out and destroy cancer cells. Some patients respond well to immunotherapy, others do not. However, response in the 鈥減oor responders鈥� can improve significantly if they are treated with fecal bacteria from 鈥済ood responders.鈥� It doesn鈥檛 work in all cases, but the results so far have been encouraging enough to organize larger trials.
The eventual goal is to identify the specific bacteria responsible for the improved response. So far, what we do know from a 2021 study is that melanoma patients who eat a high-fibre diet are more likely to respond favourably to immunotherapy. Shades of Dr. Abernethy鈥檚 dietary recommendations. Whichever bacteria are responsible, it seems they thrive on fibre. But, as usual, more research is needed.
Where do we look for more such research? To scientists who toil away at the National Institutes of Health or are funded elsewhere by government grants. Many are to be on the chopping block as decreed by the scientifically illiterate Robert F. Kennedy Jr. It makes me sick to my stomach! I better get some GABA-enriched tea to tone down the stress.
