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Feed your friends; starve your enemies

June 03, 2019


We are born, we live, and then we die. It may be comforting to know that along this journey, we are never truly alone: Trillions of gut microbes journey with us throughout life, and if we take care of them, they allow us to live longer, healthier lives, according to the presenters in session MDD002, “Overview of Gut Microbiome, Diet, and Health,” and session MDD003, “The Role of Probiotics and Gut Microbiome on Metabolic Health: An Overview of the Clinical Science and Market Positioning of Probiotics for Weight Management and Metabolic Syndrome.”

The gut microbiome is an integral part of the human genetic landscape and helps shape immune and metabolic health throughout life. Greater gut microbial diversity is key to a more resilient and healthy gut, and the best way to increase the diversity of gut microbes is through diet, said Bruce Hamaker of Purdue University. In fact, what we eat has a far greater impact on the composition of gut microbiota than genetics. Nondigestible carbohydrates (i.e., prebiotics) are the major food source for most gut bacteria. Nondigestible carbohydrates are fermented in the colon, yielding gases such as methane and carbon dioxide and short-chain fatty acids such as butyrate, acetate, and propionate. These short-chain fatty acids lower the pH of the colon, transforming the gut into an inhospitable acidic environment for bad gut microbes. Moreover, increased production of butyrate and acetate is associated with leaner body mass; these short-chain fatty acids act as signaling molecules, stimulating the release of the satiety hormone leptin.

The U.S. weight loss market is approximately $65 billion, yet two-thirds of the U.S. population is either overweight or obese. Most of the weight management solutions and programs on the market do not appear to be working, said Kiran Krishnan of Microbiome Labs, so there must be a missing link. That missing link is utilizing diet as a vector of change for metabolic disorders, which is far more effective than standalone supplements for metabolic problems, Krishnan said. This is because a nutritious diet increases the production of good microbes in the gut while a poor diet leads to dysbiosis.

Bacteria such as Akkermansia muciniphila, Bifidobacterium species, and certain Lactobacillus species appear to be highly beneficial microbes that protect against obesity, diabetes, and chronic low-grade inflammation. These gut microbes also protect against metabolic endotoxemia, or leaky gut, which Krishnan said is the primary cause of obesity. In fact, research indicates that metabolic endotoxemia induces obesity and insulin resistance. Metabolic endotoxemia allows toxins (in particular, lipopolysaccharide) to leak from the gut and into the circulatory system. A nutritious diet including nondigestible carbohydrates promotes high diversity of protective microbial strains, which leads to a greater production of short-chain fatty acids.

Short-chain fatty acids construct well-formed tight junctions that prevent metabolic endotoxemia. Metabolic endotoxemia causes an immune response that activates chronic low-grade inflammation and is a self-perpetuating problem. Only one biomarker predicts the development of type 2 diabetes: lipopolysaccharide-induced endotoxemia. Lipopolysaccharide endotoxemia also causes leptin resistance, i.e., no appetite regulation or unchecked production of ghrelin (the hunger hormone). If the gut and the brain cannot communicate, then obesity and metabolic syndrome can never or resolved, said Krishnan.

Can probiotics be used for metabolic health and weight management? There is evidence that certain strains can be beneficial in improving body composition, Krishnan said; however, their mechanisms of action are not yet known. More research is needed in this area, but experts suggest that probiotics for weight management and metabolic disease should be consumed as part of a healthy diet, not on their own. Krishnan said that the most powerful biotics approach to tackling obesity and metabolic disease would be the use of a symbiotic—a combination of a prebiotic and a probiotic. It thus appears that a nutritious diet including prebiotics and probiotics will not only promote good health but will ensure that we have a diverse group of microscopic friends that will stick with us throughout life, helping us along the way.