Friends in low places preserve gut health

Figure 1: Commensal bacteria belonging to the Clostridiales order help to control inflammation in the mammalian gut. Credit: Centers for Disease Control and Prevention

The bacterial communities that live in our intestines should not be considered freeloaders—they contribute substantially to our well-being in a number of ways, including assisting in the breakdown of otherwise indigestible dietary fiber. Hiroshi Ohno from the RIKEN Center for Integrative Medical Sciences and colleagues have now discovered a mechanism by which this digestive assistance also helps to prevent gut inflammation.

Bacteria belonging to the order Clostridiales are known to metabolize indigestible to produce metabolites, such as short-chain fatty acids (SCFAs). Ohno's team found that mice lacking gut including Clostridiales exhibit bloating within the cecum—the start of the large intestine—after consuming a high-fiber diet. However, this problem could be repaired by transplanting a Clostridiales-enriched gut bacterial community (Fig. 1).

In other recent work, Ohno and his colleagues demonstrated that these same bacteria stimulate regulatory T (Treg) , which specifically prevent the immune system from overreacting. Ohno suspected that this and his most-recent observation might be connected. "This led us to hypothesize that bacterial metabolism of dietary fiber may be the cause of Treg induction," he says.

After searching for metabolic products that were elevated following consumption of a high-fiber diet, the researchers focused on one SCFA, butyrate, as a likely candidate. Butyrate proved capable of converting immature 'naive' T cells into Treg cells in culture, and a maize starch diet that had been chemically enriched with butyrate invoked a similarly potent Treg response within the mouse colon. The same butyrate-enriched maize starch diet failed to elicit Treg proliferation in mice lacking commensal microbes, suggesting that in addition to butyrate, bacterial components are required as an antigen to be recognized by naive T cells.

Butyrate modulates the activity of enzymes that introduce chemical modifications known as 'epigenetic marks' to chromosomes, which can dramatically affect gene expression, and Ohno and his colleagues identified alterations that selectively activate Treg-specific genes. "Bacterial butyrate affected the epigenetic status of naive T cells to propel their differentiation into Treg cells within the colonic tissue," he says. This resulted in a strong protective effect, and the increased numbers of Treg cells that developed following consumption of a butyrate-enriched diet ameliorated inflammation in a mouse model of colitis.

These findings may thus reveal a critical component of the pathology of human inflammatory bowel diseases as well as a potential means for treatment. Ohno and his now hope to explore whether the same mechanism is also relevant in the inflammatory response to food allergies.

More information: Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013). dx.doi.org/10.1038/nature12721

add to favorites email to friend print save as pdf

Related Stories

Unlocking the metabolic secrets of the microbiome

May 03, 2011

The number of bacterial cells living in and on our bodies outnumbers our own cells ten to one. But the identity of all those bugs and just what exactly our relationship to all of them really is remains rather fuzzy. Now, ...

Recommended for you

Team finds key signaling pathway in cause of preeclampsia

18 hours ago

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

22 hours ago

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments