The Human Microbiome and Obesity: Moving beyond Associations

Abstract

Mounting evidence indicates that the gut microbiome responds to diet, antibiotics, and other external stimuli with speed and high precision and in ways that impact a variety of metabolic conditions including obesity and non-alcoholic fatty liver disease. Despite a decade of research establishing a strong association between the gut microbiota and obesity in humans, a causal relationship and the underlying mechanism remain outstanding. Several technological and methodological limitations in obesity and microbiome research have made it difficult to establish causality in this complex relationship. Additionally, limited collaborative interaction between microbiome and obesity researchers has delayed progress. Here, we discuss the current status of microbiome research as it relates to understanding obesity from the perspective of both communities, outline the underlying research challenges, and suggest directions to advance the obesity-microbiome field as a whole, with particular emphasis on the development of microbiome-targeted therapies for obesity prevention and treatment.

The microbiome of translocated bacterial populations in patients with and without inflammatory bowel disease

“…38,39 The presence of viable bacteria in non-IBD controls is not unexpected given the underlying pathology in these patients. In addition, other factors that have been associated with changes to the microbiome, such as diet, 40 smoking, 41 medications 42 and obesity, 43 could not be controlled for. 4 There are several limitations to our study.…”

Influence of Early Life, Diet, and the Environment on the Microbiome

“…Since then, animal studies have shown that gut microbes can influence weight gain and adiposity by affecting host gene expression, metabolic pathways, and the gut-brain-axis. 117 Moreover, weight loss interventions have also been associated with distinct shifts in the gut microbiome. A variety of surgical weight loss intervention in humans and in animals have shown distinct and long lasting microbial profile differences.…”

Microbiome diurnal rhythmicity and its impact on host physiology and disease risk

“…Through the portal vein that connects the liver to the gastrointestinal tract, the liver is exposed to the influence of the gut microbiome. Perturbations of the gut microbiome, coupled with disturbances in gut barrier function, have been associated with common liver disorders, such as non-alcoholic fatty liver disease [138][139][140], non-alcoholic steatohepatitis [139,[141][142][143][144][145][146][147][148][149][150][151][152], alcoholic liver disease [139,140,142,145,147,148,150,151,[153][154][155][156][157][158][159][160][161][162][163][164], and liver cirrhosis [165][166][167][168][169][170]. Thus, the microbiome serves as a modulator of liver rhythmic functions.…”