Evidence that Gut Bacteria Affect the Brain

Some of the most important unknowns about diet and health center around the effect of different foods on one’s gut bacteria—also called the gut microbiome. Different types of gut bacteria like different kinds of food, so what we eat affects which types of gut bacteria flourish and which types of gut bacteria wither away.

The best types of gut bacteria do part of the processing of food and can serve as a buffer between problematic aspects of food and the intestinal wall. And the worst types of gut bacteria can themselves produce unpleasant chemicals. And even if a type of gut bacteria is neutral in and of itself, if it crowds out the worst types, that is a big service. So it matters which types of gut bacteria are flourishing.

So far, the one set of recommendations I have discussed that are heavily informed by thinking about gut bacteria are those I discuss in “What Steven Gundry's Book 'The Plant Paradox' Adds to the Principles of a Low-Insulin-Index Diet.” And I talk about evidence that eating sugar causes bad gut bacteria to thrive in “Anthony Komaroff: The Microbiome and Risk for Obesity and Diabetes.”

Possible mechanisms involving gut bacteria should keep you from being complacent about the effects of diet on your health. David Kohn’s Atlantic piece, “When Gut Bacteria Change Brain Function,” points to likely effects of gut bacteria on the brain. Here are some key passages from that article, shown by indentation, with my characterizations interleaved without indentation:

By now, the idea that gut bacteria affect a person’s health is not revolutionary. Many people know that these microbes influence digestion, allergies, and metabolism.

Putting B. fragilis bacteria into a mouse model for autism reduces repetitive behavior and symptoms that look like anxiety and being noncommunicative:

In a paper published two years ago in the journal Cell, Mazmanian and several colleagues fed B. fragilis from humans to mice with symptoms similar to autism. The treatment altered the makeup of the animals’ microbiome, and more importantly, improved their behavior: They became less anxious, communicated more with other mice, and showed less repetitive behavior.

Exactly how the microbes interact with the illness—whether as a trigger or as a shield—remains mostly a mystery. But Mazmanian and his colleagues have identified one possible link: a chemical called 4-ethylphenylsulphate, or 4EPS, which seems to be produced by gut bacteria. They’ve found that mice with symptoms of autism have blood levels of 4EPS more than 40 times higher than other mice. The link between 4EPS levels and the brain isn’t clear, but when the animals were injected with the compound, they developed autism-like symptoms.

Lactobacillus and bifidobacterium reduce anxiety-like symptoms in mice, while gut bacteria from anxious humans increases anxiety-like symptoms in mice:

Stephen Collins, a gastroenterology researcher at McMaster University in Hamilton, Ontario, has found that strains of two bacteria, lactobacillus and bifidobacterium, reduce anxiety-like behavior in mice (scientists don’t call it “anxiety” because you can’t ask a mouse how it’s feeling). Humans also carry strains of these bacteria in their guts.

Collins transferred gut bacteria from anxious humans into “germ-free” mice—animals that had been raised (very carefully) so their guts contained no bacteria at all. After the transplant, these animals also behaved more anxiously.

Humans who were fed the a favorite food of Lactobacillus and Bifidobacteria—galactooligosaccharide (GOS)—ended up with lower levels of cortisol and were drawn more to positive words:

Some subjects were fed 5.5 grams of a powdered carbohydrate known as galactooligosaccharide, or GOS, while others were given a placebo. Previous studies in mice by the same scientists had shown that this carb fostered growth of Lactobacillus and Bifidobacteria; the mice with more of these microbes also had increased levels of several neurotransmitters that affect anxiety, including one called brain-derived neurotrophic factor.

In this experiment, subjects who ingested GOS showed lower levels of a key stress hormone, cortisol, and in a test involving a series of words flashed quickly on a screen, the GOS group also focused more on positive information and less on negative.

Gut bacteria produce many chemicals that could potentially affect the brain:

It’s not yet clear how the microbiome alters the brain. Most researchers agree that microbes probably influence the brain via multiple mechanisms. Scientists have found that gut bacteria produce neurotransmitters such as serotonin, dopamine and GABA, all of which play a key role in mood (many antidepressants increase levels of these same compounds). Certain organisms also affect how people metabolize these compounds, effectively regulating the amount that circulates in the blood and brain. Gut bacteria may also generate other neuroactive chemicals, including one called butyrate, that have been linked to reduced anxiety and depression. Cryan and others have also shown that some microbes can activate the vagus nerve, the main line of communication between the gut and the brain. In addition, the microbiome is intertwined with the immune system, which itself influences mood and behavior.

Two types of effect not clearly stated in this extensive just above are the possibilities that (a) certain gut bacteria could intercept and neutralize chemicals from food that might otherwise affect the brain and (b) certain gut bacteria could intercept and neutralize chemicals that might otherwise damage the intestinal wall, which in turn would let other nasty chemicals into the bloodstream.

Why would certain types of gut bacteria do helpful things? One possibility is that it might help aid the spread of that type of gut bacteria:

Cryan suggests that over time, at least a few microbes have developed ways to shape their hosts’ behavior for their own ends. Modifying mood is a plausible microbial survival strategy, he argues that “happy people tend to be more social. And the more social we are, the more chances the microbes have to exchange and spread.”

The other possibility is that, other things equal, killing off one’s host is bad for the spread of one’s type of bacteria. But it takes many humans dying over a long period of time for this to create significant cumulative evolutionary pressure towards nice bacteria, and any change in dietary habits can put in motion a much quicker process of nasty bacteria flourishing.


There are many things about gut bacteria that we still don’t understand. For a simple example, to what extent do gut bacteria themselves burn calories so that get absorbed through the intestinal wall are less than the calories that are eaten?

In terms of guesswork, an argument I alluded to above is that it takes many generations of humans, with those infested with bad gut bacteria being more likely to die, in order to cumulate a significant evolutionary advantage to nice gut bacteria. That is, coevolution of gut bacteria with humans requires many human generations, since it is differential survival of the human hosts that gives an advantage to the nice bacteria. Other than evolutionary pressures from the deaths or degradation of human hosts, evolutionary pressures on bacteria are all for the benefit of the bacteria, not for the benefit of humans.

Evolutionary pressures on bacteria for the benefit of the bacteria, without regard to their effects on their human hosts, can act very fast. It is likely to be quite delicate to maintain a short-run equilibrium that keeps a nice type of bacteria ahead of the nasty type of bacteria for long enough to gain the long-run benefit from human hosts not dying as much. Dietary changes could easily disrupt that short-run equilibrium so things shift toward a nasty type of bacteria that persist for a long time before the long-run disadvantage of killing of human hosts takes its toll on that type of bacteria.

So the bottom line is that it is wise to eat in a way that is close to how our ancestors ate over the period of time when gut bacteria coevolved to be nice to humans. Eating in a newfangled way that changes the competitive environment for bacteria is likely to hurt the competitive strength of some of the old friends we have among gut bacteria. “True paleo” (as distinct from what is called “paleo”) is what I talk about in ““What Steven Gundry's Book 'The Plant Paradox' Adds to the Principles of a Low-Insulin-Index Diet.”

In principle, we should be able to figure out the details of which bacteria we need to take care of to stay healthy and what we need to do for them. In the meanwhile, before we have figured everything out about the gut microbiome, eating in a fairly traditional “true paleo” way is a good precautionary strategy.

Don’t miss my other posts on diet and health:

I. The Basics

II. Sugar as a Slow Poison

III. Anti-Cancer Eating

IV. Eating Tips

V. Calories In/Calories Out

VI. Wonkish

VIII. Debates about Particular Foods and about Exercise

IX. Gary Taubes

X. Twitter Discussions

XI. On My Interest in Diet and Health

See the last section of "Five Books That Have Changed My Life" and the podcast "Miles Kimball Explains to Tracy Alloway and Joe Weisenthal Why Losing Weight Is Like Defeating Inflation." If you want to know how I got interested in diet and health and fighting obesity and a little more about my own experience with weight gain and weight loss, see “Diana Kimball: Listening Creates Possibilities and my post "A Barycentric Autobiography.