The Gut Microbiome in Obesity: A New Frontier in Therapeutic Targets

A Message from Dr. Christopher Still

Christopher Still, DO, FACN, FACP, Co-Clinical Editor, Bariatric Times; Medical Director for the Center for Nutrition and Weight Management, and Director for Geisinger Obesity Research Institute, Geisinger Medical Center, Danville, Pennsylvania.

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Dear Readers,

In this issue of Bariatric Times, we feature a fantastic article and CEU-accredited activity in our Integrated Health Continuing Education Department that explores the role that the human microbiome plays in obesity-related health. The microbiome, which refers to the collective genomes of microbes that live within and on the human body, and its effect on body processes is a promising new area of research. The study of the gut microbiome, in particular, represents a new frontier in therapeutic targets for management of chronic diseases, such as inflammatory bowel disease (IBD), fatty liver disease, and obesity.

The gut microbiome, which is of highest interest when exploring composition as it relates to obesity, comprises a complex system of microbes, including bacteria, fungi, protists, archaea, and viruses, that populate the human gastrointestinal tract. Extensive research has established the involvement of the gut microbiome in human metabolism, nutrition, physiology, and immune function, and we now know that an imbalance in the gut microbiota can significantly impact our health. For instance, recent research reinforces the hypothesis of dysbiosis of the gut microbiome and diet as relevant mechanisms underlying IBD pathogenesis.[1] Even slight dysbiosis in the intestinal microenvironment has been shown to increase host susceptibility to Clostridium difficile infection, an infectious Gram-positive spore-forming bacillus microorganism of the gastrointestinal tract.[2]

Further study into the gut microbiome that observes changes after fecal microbiota transplantation is fascinating, and researchers have found that transplanting microbiota between lean and obese mice models changes the lean subject’s metabolic profile, which leads to an increased rate of fat deposition.[3,4] These observations provide evidence that this complex system is indeed related to obesity.

At Geisinger, we are interested in examining microbiome changes in humans that might occur during different stages of weight loss. Currently, we are collecting stool samples as part of a longitudinal study of changes in gut microbiome before and after bariatric surgery. We have samples from over 1,000 patients and will be observing gut microbiome changes in individuals who have lost a significant amount of weight after surgery, individuals who have not lost as much weight as expected, and those who demonstrated improvement or resolution of type 2 diabetes mellitus (T2DM) and/or fatty liver disease. Our hope is to discover and understand specific microbiota changes in relation to obesity and translate this understanding into changes in clinical practice. For instance, if we find that patients who experienced the most success following surgery had a particular balance in bacterial phyla Bacteroidetes and Firmicutes, then perhaps we could mimic that ratio in other patients using dietary interventions. Generally, research shows that individuals with obesity typically display a relative decrease in Bacteroidetes and an increase in Firmicutes, whereas the opposite is expected in lean individuals.[5]

However, manipulating the microbiome to an ideal balance is likely not as easy as it sounds. Currently, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation represent the most widespread options. There are also studies that are examining dietary components, specifically emulsifiers, ubiquitous components of processed foods, and their role in altering the gut microbiome. Data are showing that emulsifiers might be what is increasing the incidence of IBD, which has been observed since the mid-20th century, and the increased societal incidence of obesity/metabolic syndrome. Moreover, efforts are being made to identify foods with anti-inflammatory properties, which could possibly be effective in chronic inflammatory disease improvement.

Emerging research focused on the human microbiome suggests that gut microbiota plays an important role in metabolic processes. As we strive to identify factors influencing obesity, further studies into microbiome and its interactions with the endocrine and digestive systems and the brain will lead to a better understanding of these processes, ultimately resulting in more customized and effective interventions in obesity prevention and management.

Sincerely,

Christopher Still, DO, FACN, FACP

References

1. Rapozo DC, Bernardazzi C, de Souza HS. Diet and microbiota in inflammatory bowel disease: The gut in disharmony. World J Gastroenterol. 2017;23(12):2124–2140.
2. Bien J, Palagani V, Bozko P. The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease? Therap Adv Gastroenterol. 2013;6(1):53–68.
3. Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–1031.
4. Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214.
5. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007;104(3):979–984.
6. Chassaing B, Koren O, Goodrich JK, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015 Mar 5;519(7541):92-6.

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