The Two Sides of Bacteroides fragilis

Back in May, 2018, I wrote about Bacteriodes fragilis (B. fragilis), a species of bacteria some strains of which are toxic, some of which are highly beneficial.  The main thrust of that post was about how our immune system, when functioning properly, can recognize a probiotic species…and while antibodies ordinarily mark “invaders” for destruction, the main antibody of our digestive system, IgA, actually binds to B. fragilis to help it colonize the intestine.

One of the researchers involved in that work stated, “It is surprising to find that an immune response actually helps beneficial bacteria to thrive, which in turn helps the host thrive….The study of immunology has mainly been in the context of pathogenic bacteria. But there are trillions of bacteria in the gut, and most of the time none of them are making you sick. Our study shows that there is active immune recognition of these bacteria, but it helps rather than hinders them. This suggests that the immune system is more than just a defense system and antibodies are more than just weapons.”[i]

Fostering the growth of this beneficial species is just that crucial to our health.  Thus, I’ve tried to keep an eye out for anything new on it.

I was happy to read another article[ii] this week about B. fragilis. It is a truly fascinating organism that reminds me of the poem by Henry Wadsworth Longfellow:

There was a little girl,

Who had a little curl,

Right in the middle of her forehead.

When she was good,

She was very good indeed,

But when she was bad she was horrid.

A little about the organism first:  B. fragilis is comprises about 1-2% of fecal bacteria, and colonization with it begins at birth.  Diet, life style, exercise, medicines and so forth all affect levels of the species, with diet being by far the most crucial. Age is also a factor:  levels seem to decrease as we get older.  Exercise, however, boosts levels.  Colonization seems to rely upon a “tolerant host immune system that allows colonization of the gut, and certain host immune molecules (e.g. IgA) have even been shown to stabilize bacterial colonization.”  To sum up, healthy humans seem to host a meaningful number of the non-toxic strains of this organism, which is pretty indispensable for good health, as I will describe.

Non-toxic B. fragilis (NTBF) inhibits inflammation in various organs of the human body, including the digestive tract, obviously, but also the brain, the lungs, etc.  These probiotic strains “…inhibit infection by pathogenic bacteria…” and have actually been found to support cancer treatments.  The main functional molecule secreted by these bacteria is a polysaccharide called PSA, which enhances the production of T-regulatory cells – those which produce anti-inflammatory cytokines and which therefore, modulate the inflammatory response.  (I talk about these all the time in regards to helminths and our missing macrobiome.  You can read more about that many times on my blog, including here.)

NTBF also produces short-chain fatty acids in abundance, further reducing inflammation, improving GI health and the integrity of the gut barrier.

A few high points:

1. “Studies of mice indicate that PSA released by B. fragilis …has significant effects on the treatment of experimental colitis and may protect against weight loss and inflammation…” In animal models, PSA not only prevents colitis – it actually cures it.
2. In a rat model, a strain of NTBF alleviates antibiotics-associated diarrhea.
3. This is pretty amazing:
   • As a powerful anti-inflammatory and immune system regulator (i.e. booster of Treg), NTBF appears to inhibit “…central nervous system demyelinating disease” (ie. multiple sclerosis).
   • In mice, when pregnant mothers have their immune systems stimulated (ie. maternal immune activation( MIA)), pups are born with characteristics of autism, including social impairments as well as leaky gut. “However, oral administration of B. fragilis ameliorated both neurodevelopmental disorders and gastrointestinal abnormalities in these deficient offspring.”
4. NTBF seems to protect against airway inflammation and asthma.
5. It also seems protective against pathogenic bacteria, including, interestingly, Bartonella, a tick-borne disease.
6. As mentioned earlier, it also appears to promote anti-cancer therapies, and an in vivo experiment suggests it may prevent the development of colon cancer.

And now for the horrid:

ETBF (enterotoxigenic B. fragilis) – the strains that comprise the dark side of the species – “…have been implicated in various conditions involving intestinal and extra-intestinal infections, including inflammatory bowel disease (IBD)…systemic inflammation and neurological disorders.”  (Interestingly, healthy adults may harbor ETFB as well, although it is asymptomatic.)  There is a virulent factor, B. fragilis toxin, that can disrupt the integrity of the intestinal mucosa and induce inflammatory bowel disease and colorectal cancer.  In fact, “…a significant association has been detected between the proportion of ETBF and colorectal carcinogenesis.”

Because of the inflammation-induced leaky gut caused by ETFB, it may actually enter the blood stream causing major systemic inflammation.  Toxins from the organism “…may also pass through the blood-brain barrier and gradually promote the development of Alzheimer’s disease…”  In fact, the toxins produced by ETBF may be “…exceptionally potent drivers of pro-inflammatory degenerative neuropathology.”

The species is particularly adept at adapting itself to antibiotics, so resistance is a major problem.

On the bright side, NTBF is now on the short-list of what is being called “next generation probiotics,” along with organisms you are all familiar with, like Akkermansia. The research currently suggests that it may well turn out to be a highly effective means of eliminating other bacterial infections as well as a treatment for leaky gut and more.  I’ll stay on top of this one – hopefully it won’t be too many years before these “new generation probiotics” become available commercially.

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[i] https://www.sciencedaily.com/releases/2018/05/180504133624.htm

[ii] Sun, F, Zhang, Q, Zhao, J, Zhang, H, Shai, Q, Chen, W. A potential species of next-generation probiotics? The dark and light sides of Bacteroides fragilis in health. Food Researcher International. 2019;126.  https://doi.org/10.1016/j.foodres.2019.108590