Cross-Talk Between Bile Acids and Gastro-Intestinal and Thermogenic Hormones: Clues from Bariatric Surgery

Abstract

Obesity is rapidly increasing and has reached epidemic features worldwide. It´s linked to insulin resistance, systemic low-grade inflammation and common pathogenic pathways with a number of comorbidities (including cancer), leading to high mortality rates. Besides change of lifestyles (diet and physical exercise) and pharmacological therapy, bariatric surgery is able to rapidly improve several metabolic and morphologic features associated with excessive fat storage, and currently represents an in vivo model to study the pathogenic mechanisms underlying obesity and obesity-related complications. Studies on obese subjects undergoing bariatric surgery find that the effects of surgery are not simply secondary to gastric mechanical restriction and malabsorption which induce body weight loss. In fact, some surgical procedures positively modify key pathways involving the intestine, bile acids, receptor signaling, gut microbiota, hormones and thermogenesis, leading to systemic metabolic changes. Furthermore, bariatric surgery represents a suitable model to evaluate the gene-environment interaction and some epigenetic mechanisms linking obesity and insulin resistance to metabolic diseases.

Microbial regulation of organismal energy homeostasis

“…Bariatric surgery is an efficient intervention leading to weight loss and improving glycaemic control. In addition to positively modulating bile acids and gut hormones, this surgery leads to dramatics shifts in the gut microbiota composition, a major contributor in bariatric surgery-mediated health effects [203][204][205] . However, for severe obesity, recent data are jeopardizing this general thought, as the bacterial species associated with a low bacterial richness (before surgery) were only marginally modified after the bariatric surgery despite numerous metabolic improvements 206,207 .…”

Liver Steatosis, Gut-Liver Axis, Microbiome and Environmental Factors. A Never-Ending Bidirectional Cross-Talk

“…The interaction is bidirectional since gut-derived products permeate the intestine going through the portal vein to the liver, while liver-secreted bile and antibodies are flowing from the liver through the intestine. Moreover, BAs are markedly influenced by the intestinal microbiome but also control the intestinal microbiome, besides their classical physiologic functions that allow food digestion and absorption, as well as stimulation of nuclear receptors and specific receptors at the intestinal level [ 12 , 89 , 90 ]. The gut barrier integrity results from a balanced cross-talk between microbiome, mucus, intestinal cells, immunological system and gut-vascular barrier.…”

“…A first level of the gut barrier is the resident microbiota, which is composed by hundred trillions of microorganisms [ 94 ], with more than 10 times the genes of the human genome and a weight of about 1–2 kg [ 95 ]. The gut microbiota plays a key role in nutrient and vitamin processing, and biotransformation of intestinal primary BAs to secondary BAs [ 12 , 89 , 96 ].…”

“…As mentioned earlier, the intestinal microbiota is essential during the process of enterohepatic circulation of primary BAs. At the level of the colon, the bile acids undergo complex biotransformation by the resident microbiota and are transformed into secondary BAs [ 12 , 89 , 270 ]. Under specific circumstances, the dysbiosis may contribute to hepatocellular injury because of increased deconjugation of BAs (i.e., production of more cytotoxic secondary bile acids) and inactivation of hepatic lipotropes (i.e., choline).…”

Mikrobiom und metabolische/bariatrische Chirurgie

“…Grundlagenwissenschaftliche Studien konnten zeigen, dass der Darm als physiologische Schaltzentrale dient und nach anatomischer Umstellung wie beispielsweise nach einer Magenbypass-Operation veränderte neuronale und endokrine Signale an unterschiedliche Organsysteme aussendet [18,19].…”