Microbial Reprogramming Inhibits Western Diet-Associated Obesity

Abstract

A recent epidemiological study showed that eating ‘fast food’ items such as potato chips increased likelihood of obesity, whereas eating yogurt prevented age-associated weight gain in humans. It was demonstrated previously in animal models of obesity that the immune system plays a critical role in this process. Here we examined human subjects and mouse models consuming Westernized ‘fast food’ diet, and found CD4+ T helper (Th)17-biased immunity and changes in microbial communities and abdominal fat with obesity after eating the Western chow. In striking contrast, eating probiotic yogurt together with Western chow inhibited age-associated weight gain. We went on to test whether a bacteria found in yogurt may serve to lessen fat pathology by using purified Lactobacillus reuteri ATCC 6475 in drinking water. Surprisingly, we discovered that oral L. reuteri therapy alone was sufficient to change the pro-inflammatory immune cell profile and prevent abdominal fat pathology and age-associated weight gain in mice regardless of their baseline diet. These beneficial microbe effects were transferable into naïve recipient animals by purified CD4+ T cells alone. Specifically, bacterial effects depended upon active immune tolerance by induction of Foxp3+ regulatory T cells (Treg) and interleukin (Il)-10, without significantly changing the gut microbial ecology or reducing ad libitum caloric intake. Our finding that microbial targeting restored CD4+ T cell balance and yielded significantly leaner animals regardless of their dietary ‘fast food’ indiscretions suggests population-based approaches for weight management and enhancing public health in industrialized societies.

Epithelial Adhesion Mediated by Pilin SpaC Is Required for Lactobacillus rhamnosus GG-Induced Cellular Responses

“…While the former are often bacteria with fermentative capacity, recent work suggests that mucosa-associated microbes are responsible for many of the physiological functions normally attributed to the entire population. These taxa, which include Lactobacillus, Bifidobacterium, and Bacteroides, have a wide variety of functions ascribed to them: for example, Lactobacillus reuteri can inhibit Western-diet-associated obesity (26), Bifidobacterium infantis-conditioned medium enhances intestinal epithelial cell barrier function (27), Bacteroides thetaiotaomicron is known to induce gene regulatory events in the upper GI tract (28), and Bacteroides fragilis has been shown to influence immune development and enhance barrier function (29). Studies from our research group and others have shown that lactobacilli stimulate epithelial ROS generation and activate motility and proliferation events.…”

Dietary Microbes Modulate Transgenerational Cancer Risk

“…Impaired regulatory capacity leads to uncontrolled immune inflammatory responses, obesity and cancer later in life (2, 3). Our recent studies in mice have shown that Westernized diet (NWD)-associated obesity and cancer coincide with changes in gastrointestinal (GI) tract microbial communities and immune regulatory capacity preventable by dietary enrichment with beneficial bacteria(4–7). We test here whether these postulated effects of gut microbes transcend generations.…”

Oral Lactobacillus Counts Predict Weight Gain Susceptibility: A 6-Year Follow-Up Study

“…Through biopsies in the duodenal mucosa of healthy adults receiving either live or heat-killed L. plantarum , Baarlen et al [15] demonstrated a regulation of the key inflammatory transcription factor in subjects receiving live bacteria. Supporting this immunomodulatory role of Lactobacillus , Poutahidis et al [16] showed that Lactobacillus reuteri administered in the drinking water facilitated resistance to diet-induced obesity, despite L. reuteri failing to colonize the intestinal cavity. Subsequent experiments confirmed that L. reuteri induced an adipose-specific increase of anti-inflammatory regulatory T cells.…”