Direct Link Between Diet, the Microbiome and the Immune System Found

This is an awesome piece of research out of Harvard Medical School, along with Brigham and Women’s Hospital, Seoul National University, and Monash University in Australia.  They have essentially found a key piece of evidence that what you eat directly affects your immune system.[i]

In mice, the scientists followed the digestion, and subsequent breakdown, of dietary amino acids (branched-chain amino acids). For those unfamiliar, amino acids are the building blocks of proteins. When you eat protein, your body breaks it down into amino acids, which it then uses to create the proteins necessary for your body to function.

The researchers saw that our old friend, Bacteroides fragilis (remember this post on the good and bad of this particular bacterium?!) takes up these branched-chain amino acids and, using a specific enzyme, converts them into a sugar-lipid (fat) which are also branch-chained.  These molecules are released by the bacteria, and then picked up by special immune cells, called antigen-presenting cells. These immune cells induce natural NK T cells to “…exercise their immunoregulatory response through upregulating inflammation-controlling genes and immune-regulatory chemicals.”[ii]  That is, these molecules released by branch-chain-amino- acid- eating B. fragilis have a downstream anti-inflammatory effect.  (It turns out that NK T cells “…line the human gastrointestinal tract and the lungs and are also found in the liver and spleen, they likely play a significant role in immune regulation.”)

Interestingly, each of the 3 different branch-chained amino acids consumed by the mice led to different structures of the bacterial sugar-lipid molecule, which led to a different pattern of binding to the immune cells.  Said one of the researchers involved, “Our findings yield fascinating insights about the microbiome, diet, and immune function and provide interesting clues about how molecules made by our inner neighbors can be used to design therapies…”

Mice with ulcerative colitis were treated with these B.fragilis sugar-lipid molecules and compared to untreated controls (with UC).  The intestinal cells of these treated animals showed minimal signs of colonic inflammation. This work follows previous research by the same team published in 2014.  At that time, they realized that the anti-inflammatory effects of B.fragilis were due to it releasing some kind of molecule that spoke directly to the immune system but now, they have figured out the source (i.e. branch-chained amino acids) and the structure of that molecule (also a branch-chain structure), and it is the latter that causes the molecule to induce an anti-inflammatory effect, as opposed to a pro-inflammatory effect.

By the way, non-branched amino acids did not induce the anti-inflammatory effects.  So,  what foods contain branched-chain amino acids, you ask?  Dairy products, beef, poultry, fish, eggs, beans, legumes, whole wheat and brown rice, for starters.

These anti-inflammatory molecules can be made in the lab so in the future, the scientists hope that this can be turned into a medication for those with IBD and other inflammatory illnesses:  “We can never isolate enough of these immune-modulatory molecules from bacteria for therapeutic use, but the beauty of this is now we can synthesize them in the lab…The idea would be that we’d have a drug that can modulate inflammation in the colon and beyond.”

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[i] Oh, S.F., Praveena, T., Song, H. et al. Host immunomodulatory lipids created by symbionts from dietary amino acids. Nature (2021). https://doi.org/10.1038/s41586-021-04083-0

[ii] https://hms.harvard.edu/news/diet-gut-microbes-immunity