Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans – towards treatment with probiotics

Abstract

Changes in the gut microbiota are associated with metabolic disorders, such as overweight and elevated blood glucose. Mouse studies have shown that gut microbiota can regulate metabolism with a mechanism related to gut barrier function. An impaired gut barrier permits the translocation of bacteria and their components which, when in contact with the sub-mucosal immune system, evoke metabolic inflammation and distract signalling in metabolically active tissues. Despite thorough research of the topic in animals, the hypothesis is yet to be proven in humans. Cross-sectional studies have shown that certain bacterial populations - such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Methanobrevibacter smithii and Christensenellaceae - are better represented in lean individuals compared to those who are overweight or metabolically unhealthy. Although these differences reflect those seen in mice, it is possible that they are caused by different dietary or other lifestyle habits. Diet has an indisputable influence on gut microbiota making it very difficult to draw conclusions on microbiota-host interactions from cross-sectional studies. Certain research areas do, however, indicate that gut microbiota could causally influence metabolism. Several studies show that antibiotic use in infancy increases body weight in later childhood. Also, probiotics are emerging as a potential therapy for metabolic syndrome. In fact, a handful of human studies and numerous animal studies show promise for probiotics in reducing blood glucose levels or improving insulin sensitivity. For weight management human evidence is scarcer. Nevertheless, it is becoming increasingly recognised that gut microbiota plays a part regulating metabolism, also in humans, which gives rise to novel opportunities for preventative and treatment strategies.

Function of Akkermansia muciniphila in Obesity: Interactions With Lipid Metabolism, Immune Response and Gut Systems

“…Dietary interventions for reducing obesity have been suggested that focus on calorie restriction, energy reduction, or a diet rich in prebiotic fibers, all of which are associated with an increased level of A. muciniphila in the host (Verhoog et al, 2019). For example, clinical trials have shown a significant increase in A. muciniphila in a calorie restriction study of 49 overweight and obese adults (Stenman et al, 2016). Diets rich in prebiotic fiber increased the number of A. muciniphila in the microbiome (Gomez-Gallego et al, 2016).…”

Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults—Randomized Controlled Trial

“…Since the discovery of a link between gut microbiota and obesity in 2006 (Turnbaugh et al, 2006, Ley et al, 2006), increasing evidence has been presented to suggest a causal relationship between gut microbiota and metabolic disorders (Stenman et al, 2015a). …”

Targeting the gastrointestinal tract to treat type 2 diabetes

“…Further, chronic treatment with dietary phenols from grapes, or cranberry extract, improved glucose tolerance and insulin sensitivity which was hypothesized to be due to A. muciniphila abundance (Anhe et al 2015, Roopchand et al 2015. Although A. muciniphila remains to be tested in humans, this is one example in an ever-expanding list of potential probiotics that could help lower glucose levels in type 2 diabetes (Le Barz et al 2015, Stenman et al 2015a. It is interesting to note that metformin treatment has been shown to alter the gut microbiota, with chronic treatment resulting in A. muciniphila abundance, as well as changes in bile acid levels, suggesting a gut microbiota-mediated role for metformin treatment (Lien et al 2014, Napolitano et al 2014, Shin et al 2014.…”