Probiotics and other microbiome manipulations have been touted as cures to everything from obesity to colitis to allergies and autism. Certainly the potential for these agents and methods are exciting, but what where is the line, now, between dangerous hype and the state of the art research being done?
The perfect way to answer that question was a symposium this past week at Harvard Medical School on gut health, microbiota, and probiotics, bringing together world experts in the field.[...]
His lab has worked out fascinating interactions between how the microbes in the gut metabolize bile acids and downstream changes in how the liver processes our food, which could explain a piece of how our gut could be a key battleground in the fight against obesity and diabetes.
In both human and rodent studies, increasing obesity, insulin resistance, and fasting glucose levels correlate linearly with decreasing distance between gut bacteria and the cells lining the intestine. This invasion of bacteria on the front lines of the gut is called "bacterial encroachment," reminding us that our relationship with our microbiota is best characterized as "frenemies." Andrew Gewirtz leads a team at Penn that published the sobering paper in Nature last year, showing how modest amounts of emulsifying agents nearly universally found in processed food damaged the microbiome and intestinal cells, causing colitis in mice. He made the sensible recommendation to avoid processed food in favor of eating fresh, whole foods.
He's also been able to reverse some damaging effects of more processed, purified diets in mice by adding the fermentable fiber inulin to their chow. The inulin feeds the microbiota and makes them more diverse and robust. However, along the lines of the "frenemies" designation, immune compromised mice got sick when fed inulin, meaning we have to be careful about making recommendations for fiber blooming of our gut microbes. It may make sense to use multiple step treatments, eliminating pathogens with temporary low fermentable fiber diets and possibly antibiotics, then adding in more friendly probiotics, feeding them with fiber. These complex protocols have yet to be studied in a systematic way in humans and remain experimental.
On the second day of the symposium, several scientists, including one of my favorites, psychiatrist Ted Dinan from University of College Cork, spoke about the evolving work on interactions between the gut and the brain. He's studied small but significant differences in cognition and stress tolerance in mice born via c-section vs. vaginally, and, crucially, found some similar differences in young adult humans. He showed data from a study taking fecal transplants from depressed individuals into rats, leading to dramatic changes in behavior in these rats when they became more anxious and anhedonic. They also had elevated levels of inflammation compared to rats who got fecal transplants from non-depressed, healthy humans.
All the speakers linking gut and brain health mentioned how microbiota affect the metabolism of serotonin, a key behavioral neurotransmitter, and Elaine Hsiao, PhD of UCLA showed some of her work illuminating this complex process down to the molecular level. In addition, many microbes make neurotransmitters in the gut, which can send signals to the brain via the vagus nerve. In previous studies, certain strains of probiotics have been shown to decrease anxiety in rats, and this effect was lost by cutting the vagus nerve. Dinan has also shown improved cognition in humans using the probiotic b. longum.
He made a key point that these measured microbial effects in humans are modest but significant. If a new class of treatments for depression or anxiety is made from probiotics, they will likely be most useful for mild depression or anxiety. Most folks who experience depressive disorders have more mild cases, and many people for various reasons don't have access to the psychotherapy that is first line for milder depression. "Psychobiotics" could be an inexpensive and low risk way to bridge the treatment gap. [...]
