Another Reason to Eat More Apples and Whole Grain: How Inflammation and Hematopoiesis are Affected by Dietary Fiber and GI Microbes

One day, sometime in the 1970s, when I was a medical student attending Medicine Grand Rounds, I remember hearing Professor Denis Burkitt extol the wonders of dietary fiber, arguing persuasively that, compared with Westerners, Africans experience a lower incidence of diseases ranging from colon cancer to hemorrhoids because their diet is relatively fiber-rich. The mechanisms that accounted for the beneficial effects of high dietary fiber were unclear at the time, and the simple concept of more rapid stool transit time was invoked to explain the difference.¹  Subsequent investigation, however, has uncovered an intricate relationship between dietary fiber, the microbes in our gut, and both intestinal and systemic immuno/inflammatory processes. Dietary fibers are complex carbohydrates that can be fermented by certain species of gut bacteria, leading to production of bioactive products including short-chain fatty acids (SCFAs). SCFAs serve as an energy source for certain bacteria, but they also provide fuel for intestinal epithelial cells. Available evidence suggests that their effects are exerted through a surprisingly diverse range of mechanisms including engagement of G-protein coupled receptors and inhibition of histone deacetylase activity. And SCFAs such as acetate, propionate, and butyrate are not confined to the gut, being disseminated diffusely after entering the circulatory system and thereby becoming available to participate in systemic processes. Now, from Dr. Aurélien Trompette and colleagues at the University of Lausanne, in Lausanne, Switzerland, we learn how generation of SCFAs by gut microbiota metabolism both ameliorates allergic airway inflammation (AAI) and drives hematopoiesis.

To examine the role that dietary fiber plays in modulating AAI, mice were fed a standard diet containing 4 percent fiber or a low-fiber diet containing 0.3 percent fiber and exposed to house dust mites. Compared with mice fed the low fiber diet, mice fed the higher-fiber diet had less lung eosinophil and lymphocyte infiltration, reduced production of cytokines IL-4, IL-5, IL-13, IL17A, lower levels of IgE, and IgG1 antibodies against the dust mite. Mice fed a high-fiber diet had less severe AAI in response to methacholine, and lung DCs were less activated as shown by lower expression of CD40, CD80, PDL-1, and PDL-2. Complementary studies confirmed these findings in mice that were fed a diet supplemented with the fermentable fiber pectin (a substance enriched in apples).

Dietary fiber changed the gut and lung microbiota by enhancing bacterial diversity, especially in the proportion of bacteroidaceae and bifidobacteriaceae, both potent fermenters of fiber into SFCAs. Both serum and cecal acetate and propionate levels were higher in the high-fiber fed animals. To show that increased SCFAs mediate the protective effect of fiber against inflammation, mice were fed acetate or propionate. One day after mice were given an intranasal house mite challenge, inflammation was similar in control- and propionatefed animals, but after two to four days, eosinophils and cytokine levels in the lung were reduced in SCFAs-treated mice. This protective effect was dependent on G-protein coupled receptor 41 (also called free fatty acid receptor 3). There was impaired TH₂ differentiation and decreased dendritic cell (DC) activation in SCFAs-treated mice four days after the challenge. Other experiments showed that propionate enhanced hematopoiesis, increasing both common DCs and macrophage DCs in the bone marrow.