Prevotella: The Good, The Bad and The Ugly

How many times on this blog have a talked about how insanely complex is the human biome?  Yesterday, I had one of those moments where I almost threw up my hands and thought, “I give up!”  Everything seems so damn contradictory.  Then, of course, being me, I dig in my heels and keep reading, having faith that someday, scientists will figure this all out.

I have mentioned the Prevotella family (and a type of it called Prevotella copri (P. copri)) of bacteria over and over on this blog.  When I first started to read about it, it was always in the context of it being a probiotic species, associated with high-fiber, non-Western diets.   Just a few examples: in late March of this year, I wrote about the maternal microbiome and the risk of developing food allergies in babies.  From that post:  “They found that 20% of the babies that did not develop allergies had P.copri in their stool samples versus only 8% of babies with allergies: the presence of P.copri in the mom’s stool sample meant less risk of developing allergy for their baby.”  Just a month before, I wrote about the microbiome in infancy and its relationship to the development of anxiety issues in toddlers:  Australian researchers found that decreased levels of Prevotella in babies was associated with behavioral issues at 2 years of age.

In April of this year, I wrote about research out of Washington University in St. Louis in which researchers analyzed the fecal microbiomes of wild chimps and gorillas, and compared these to captive chimps.   What was especially interesting about this research is that the captive animals, who were fed a high fiber diet but one made up of agrarian products as opposed to the native, non-human-grown foods eaten by the wild animals, had (from that post):  “…a higher abundance of Prevotella (including P. copri), which as you know from reading my posts these past few weeks (for example, here), is associated with a high fiber (i.e. non-western) diet.  In fact, the Congolese humans tested, who eat a non-western diet, showed the same high levels of Prevotella. The researchers postulate that this difference, between captive and wild animals, is due to the actual composition of the fibers they each eat.”  The TYPE of fiber seemed to dictate the amounts of Prevotella bacteria.

So, Prevotella is generally considered a probiotic species associated with a healthy plant-based diet, and is often found at decreased levels in the industrialized world.  So increased levels are always good right?

No.

Ugh.

To understand Prevotella‘s duel personality, it’s critical to know more the organism.   This research might be crucial in gaining that understanding:  a 2019 study in Cell Host & Microbe found that P. copri is a “…common human gut microbe that has been both positively and negatively associated with host health.”[i]  And why might this be?  Because, they state, they have found 4 different “clades” (which means a group of organism believed to have evolved from a common ancestor) of P.copri, and in non-Western cultures, all 4 are ubiquitous and co-present. However, as we began to move toward a Western diet, these ancient diverse forms of this bacteria were lost and now this diversity is “…underrepresented in Western-lifestyle populations.”  In the discussion section of this paper, the researchers state that, “A major element of Westernization has been a shift in diet over the course of the last two centuries with the advent of industrialization and food processing, from one typically high in fiber and complex carbohydrates to one high in sodium, fat, and simple sugars and low in fiber. It was previously shown that P. copri provides a host benefit in response to a high-fiber diet (but not one high in fat). The P. copri complex shows a diversity in plant-derived carbohydrate utilization which may suggest that diet is a key driver responsible for its ultimate demise in Westernized populations.”  So diet is the key driver of the shift in the kinds of P. copri we host…and now, in our current Westernized life-style, whether this bacterium is “…a positive or negative influence on health in the context of other microbiome members, diet, lifestyle, and host genetic factors” remains to be seen.  As they state, this study reveals that this one bacterial species is “far more complex than previously imagined…”

So, now to some of the negatives:

A new study out of Kings College, London,[ii]  looking at blood and stool samples of twins with genetic variations known to put individuals at risk for developing rheumatoid arthritis (RA), found that “Prevotella spp [species] in the gut microbiota are associated with the rheumatoid arthritis genotype in the absence of rheumatoid arthritis, including in individuals at high risk of developing rheumatoid arthritis. Our findings suggest that host genotype is associated with microbiota profile before disease onset.”  Genetic susceptibility plays a role in the development of the disease as does this variant of microbiome profile.[iii]

A late 2019 paper looked at what is known about the microbiome/RA risk, and points to one study in which those newly diagnosed with RA in the United States had an increased abundance of P. copri, as well as decreased abundance of other important species.[iv]  They state flat out that among studies analyzing the gut microbiomes of those with RA, “Prevotella species, especially, P. copri, are the dominant fecal microbiota in early RA patients,” and further research has homed in on this species as a primary trigger for the disease.

Consider the findings in the primate study I mention above:  different kinds of fibers (i.e. agrarian versus wild) affect the gut bacteria, and Prevotella in particular.  You really have to wonder if, once again, what we eat (even those of us who make a huge effort to eat right) is problematic.  It will be really interesting to follow this line of research to see where it ends up going.  Are we eating the wrong kind of fiber?  Is there a way to supplement with the right one, similar to what is in wild foods? Is the problem P. copri?  Or…is the problem the lack of diversity in our P. copri populations?!

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[i] Tett, A, et. al. The Prevotella copri complex comprises four distinct clades underrepresented in westernized populations.  Cell Host & Microbe. 2019;5(13):666-679. https://doi.org/10.1016/j.chom.2019.08.018

[ii] https://www.nutraingredients.com/Article/2020/07/22/Does-gut-bacteria-play-a-role-in-rheumatoid-arthritis#

[iii] Wells, PM, et. al. Associations between gut microbiota and genetic risk for rheumatoid arthritis in the absence of disease:  a cross-sectional study.  Lancet Rheumatology. 2020;2(7).   DOI:https://doi.org/10.1016/S2665-9913(20)30064-3

[iv] Maeda, Y., Takeda, K. Host–microbiota interactions in rheumatoid arthritis. Exp Mol Med 51, 1–6 (2019). https://doi.org/10.1038/s12276-019-0283-6