Although plenty of research in both animal models and humans during the last decade has explored the relationship between the gut microbiota and obesity and related metabolic disorders, the clinically relevant contribution of gut microbiota to obesity and related metabolic disorders is still unknown.
The relationship between obesity and metabolic diseases has been recently covered in a review article by Dr. Maria Carlota Dao from the Jean Mayer United States Department of Agriculture Human Nutrition Research Centre on Aging at Tufts University (Boston, Massachusets) and Dr. Karine Clément from the Institute of Cardiometabolism and Nutrition at the Assistance Publique Hôpitaux de Paris, the National Institute for Health and Medical Research (INSERM) and Sorbonne Universités in Paris (France).
The first part of the review introduces the cross-talk between the gut microbiota and both host health status and clinical outcomes in metabolic disorders. Gut microbiota is modified in obesity per se, but it is also modified due to related comorbidities such as type 2 diabetes (T2D), non-alcoholic fatty liver disease and cardiovascular diseases. In the close relationship between gut microbiota and metabolic disorders, local effects including both the gut-associated immune system and intestinal barrier are involved, as well as effects on distal organs and tissues such as the brain, liver and adipose tissue.
One of the main reasons explaining the difficulty of establishing a causal role of the gut microbiota in metabolic diseases is the fact that multiple factors (both host intrinsic characteristics and environmental factors) can affect both gut microbiota composition and function and the development of metabolic diseases. Thus, when considering the potential of gut microbiota in clinical care, the gut microbiota composition and function (e.g. focusing on metabolites synthesized from fibre metabolism by certain bacterial groups), intrinsic patient characteristics (age, gender, genetics), health status (obesity and related co-morbidities, pharmacology, and host immune response), lifestyle and environment, and epigenetic factors should be taken into account.
There is some indication that a healthy gut ecosystem is needed in maintaining the intestinal barrier’s integrity and proper immune system function and prevention of autoimmune disease or chronic inflammation. Specifically, microbial metabolites such as short-chain fatty acids (SCFAs) seem to be involved in maintaining the integrity of the intestinal epithelial barrier and controlling body weight and insulin sensitivity, which in turn can reduce hunger and satiety via a central homeostatic mechanism. Thus, the role of the gut microbiota in the aetiology of obesity and cardiometabolic disorders is partially mediated by gut microbiota itself. However, most data are derived from animal and in vitro studies, and consequently the importance of SCFA and differential SCFA availability in human energy and substrate metabolism remains to be fully established. There are plenty of ways by which gut microbiota -either directly or through its metabolites- may be involved in metabolic diseases. For instance, resveratrol from plant sources is able to change the gut microbiota composition of mice and thus prevent atherosclerosis. Altogether these findings highlight the importance of new studies focusing not only on composition of the gut microbiota, but also on its functional potential and how its metabolites can interact with the host in metabolism.
Gut microbial diversity and richness as a marker of host health is also another field covered in the review. Lower gut microbial diversity has been repeatedly identified as a specific feature in metabolic diseases. Specifically, lower diversity has been associated with greater abdominal adiposity and greater long-term weight gain. Several specific bacterial groups including butyrate-producing bacteria and Akkermansia muciniphila have been found markedly reduced and are expected to be involved in deterioration of metabolic health in obese subjects. A previous post has covered the latest scientific research behind the potential use of A. muciniphila as a next generation probiotic for improving metabolic health in overweight and obese adults. However, it is too early to know whether lower microbial diversity is a consequence or one of the causes of deterioration of host metabolic health.
The final part of the review covers how gut microbiota can be modulated to address metabolic conditions. The top factors involved in modifying gut microbiota composition are diet and drugs.
According to review co-author Dr. Karine Clément: “Gut microbiota can be modulated in many ways. The nature of the diet is key in the maintenance of gut health, especially regarding gut microbiota diversity. There is a relationship between the diversity of the diet and the diversity of gut microbiota; the more diverse the diet, the richer the gut microbiota… when switching for example from a Western to a Mediterranean diet. You can also modulate the gut microbiota by changing some food components, e.g. adding fibers or vegetables, which are known to increase the diversity of the gut microbiota or prebiotics such as soluble fibers, or by the intake of probiotics (living bacteria). However, their impact on metabolic health will have to be demonstrated. There are also very interesting examples of how specific modification of the diet by adding fibers or prebiotics can increase some beneficial bacteria in the gut, such as Akkermansia muciniphila or Faecalibacterium prausnitzii.”
When considering the role of diet and nutrition for improving metabolic health outcomes, several interventions including probiotics, prebiotics, calorie restriction, and bariatric surgery have been explored. The fact that there is still no clear answer with regard to the definition of a “healthy microbiota” and the characterization of the dysbiosis linked to metabolic disorders makes it difficult to design personalized interventions as an attempt to counteract metabolic diseases. So far, evidence of the beneficial role of different lactobacilli and bifidobacteria and vegetable fibres on metabolic diseases has been mainly obtained from animal models of dietary-induced obesity and related metabolic disorders. Besides this, the number of human studies focused on targeting the gut microbiota composition and functional diversity for metabolic disease management are still few, and it is too soon to judge their potential efficacy, especially when considering the fact that the individual responses vary according to intrinsic factors, the overall composition of diet, and their interactions. Further human studies focusing on whether calorie restriction or bariatric surgery synergize with pre or probiotic supplementation to enhance weight loss interventions are warranted.
Regarding whether these interventions in the gut microbiota could help reduce the risk of getting metabolic diseases, Dr. Clément says: “It is very well known that a dietary intervention with decreased caloric intake reduces metabolic or cardiovascular risks. As such, even a small reduction in weight (less than 10%) will reduce significantly these cardiometabolic risks. But the question is still open, whether targeting directly the gut microbiota would significantly decrease these cardiometabolic risks and improve metabolic health in human[s]. We still need more data to understand if a substantial modification of gut microbiota will impact significantly on the host biology and improve metabolic health.”
Finally, when considering the role of faecal microbiota transplantation (FMT) in the treatment of metabolic disorders, the authors say it is a useful method in animal models to study causality in the relationship between gut microbiota and human metabolic disorders. However, it is too early to use FMT as a therapy for metabolic disorders.
The review concludes that in order to move toward personalized interventions in a clinical setting in the treatment of metabolic disorders that target gut microbiota, study design, statistical power, method selection and potential confounders, such as stool consistency and pharmacology, should be taken into account in future studies. Besides this, future studies should characterize the gut microbiota and consider patient characteristics (clinical background and lifestyle) prior to the intervention, as these elements have an impact on gut microbiota composition, functionality and metabolomics outputs and clinical response to the intervention.
The publishing team of GMFH invites you to read the interview with Karine Clément at the Bdebate conference at the beginning of July 2015 in Barcelona.
Dao MC, Clément K. Gut microbiota and obesity: Concepts relevant to clinical care. Eur J Intern Med. 2017; doi: 10.1016/j.ejim.2017.10.005.