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Review

Obesity and the microbiome

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Pages 1087-1099 | Published online: 16 Jun 2015
 

Abstract

Obesity constitutes a significant and rapidly increasing public health challenge and is associated with significant co-morbidities and healthcare costs. Although undoubtedly multifactorial, research over the last decade has demonstrated that the microbes that colonize the human gut may contribute to the development of obesity through roles in polysaccharide breakdown, nutrient absorption, inflammatory responses and gut permeability. Studies have consistently shown that the Firmicutes to Bacteroidetes ratio, in particular, is increased in obesity and reduces with weight loss. In addition, we and others have shown that the methanogenic Archaea may also contribute to altered metabolism and weight gain in the host. However, much remains to be learned about the roles of different gut microbial populations in weight gain and obesity and the underlying mechanisms before we can begin to approach targeted treatments.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues
  • Obesity is one of the largest global health problems of this century, and is associated with significant healthcare and economic costs.

  • The human GI tract is host to a diverse and dynamic community of an estimated 1014 microbes, comprising approximately 1000 species that include eukaryotes, archaea and five bacterial phylae, of which Firmicutes and Bacteroidetes are predominant.

  • Gut microbes contribute to human health through roles in host metabolism and energy homeostasis, including breaking down non-digestible foods for absorption, energy harvest and vitamin synthesis, modulation of the host immune system and protection against enteric pathogens. Gut microbes can provide up to 10% of the host’s daily caloric intake.

  • The trait of obesity can be transmitted through colonization of the gut with different microbial populations. Although results vary between studies, increases in Firmicutes and decreases in Bacteroidetes are typically associated with obesity, and the reverse occurs following diet-induced weight loss or Roux-en-Y gastric bypass.

  • There are several potential mechanisms by which gut microbes may contribute to the development of obesity. These include: enhancing the absorption of monosaccharides from the gut by increasing the density of capillaries in the gut epithelium, enhancing the availability of nutrients to the host by breaking down otherwise indigestible polysaccharides, reducing the activity of fasting-induced adipose factor and increasing the cellular uptake of fatty acids and storage of triglycerides in adipocytes, increasing the inflammatory responses through the action of lipopolysaccharides, and effects on gut permeability mediated by tight junction proteins zonula occludens-1 (ZO-1) and occludin, as well as changes in the endocannabinoid system.

  • The methanogenic archaea have been particularly implicated in altered metabolism and weight gain in the host, and use hydrogen produced by neighboring microbes for the generation of methane. Also, 15% of individuals have detectable levels of methane on breath testing. Although controversial, we have found that this is associated with increased body mass index and percent body fat, and that levels of methane and hydrogen on breath testing are reduced following Roux-en-Y gastric bypass.

  • Methanogens may contribute to weight gain in the host by facilitating increased polysaccharide fermentation and nutrient production by neighboring microbes. Methane gas also slows the intestinal transit and affects gut motility, which may also allow increased time for nutrient absorption.

  • Eradication of methanogens in obese prediabetic subjects using specific antibiotics results in significant improvements in total cholesterol and LDL levels.

  • Although we have made tremendous progress, much remains to learned about the influence of gut microbes on weight gain and obesity, and the underlying mechanisms by which they do so.

Notes

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