Intestinal Microbiota Modulation in Obesity-Related Non-alcoholic Fatty Liver Disease

Abstract

Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.

Functional Interactions between Gut Microbiota Transplantation, Quercetin, and High‐Fat Diet Determine Non‐Alcoholic Fatty Liver Disease Development in Germ‐Free Mice

“…Due to the crucial role of gut microbiota and the lack of a gold standard treatment for NAFLD, strategies to modulate it, including the use of probiotics and prebiotics, emerge as potential therapeutic approaches. Recently, it has been discussed regarding the capacity of flavonoids to modulate gut microbiota composition, intestinal inflammation, and barrier integrity . Quercetin, flavonoid widely studied for its antioxidant and anti‐inflammatory properties, has demonstrated its ability to diminish lipid accumulation in the liver, ameliorate insulin resistance, and modulate lipogenic genes in animal models of metabolic syndrome and NAFLD .…”

A Network Involving Gut Microbiota, Circulating Bile Acids, and Hepatic Metabolism Genes That Protects Against Non‐Alcoholic Fatty Liver Disease

“…Similarly, it has been shown that gut microbiota transplantation from NAFLD‐prone donors can replicate the phenotype in germ‐free recipients . Underlying mechanisms are not completely understood yet, but they include dysbiosis‐induced deregulation of the intestinal barrier integrity and alterations in the metabolism of dietary and endogenous compounds, among others …”

“…The gut microbiota not only determines a differential extraction of nutrients and energy from the diet but also synthesizes a broad variety of metabolites that could modulate host metabolism, including ethanol, short‐chain fatty acids, secondary bile acids (BAs), and choline derivatives . BAs are synthetized from cholesterol in the liver and undergo metabolization by the gut microbiota in the intestine.…”

“…Having in mind the important contribution of gut microbiota to NAFLD, new strategies to modulate intestinal microbial composition of the host emerge as potential therapeutic approaches. Among them, the administration of substances with prebiotic properties such as nutritional supplements, probiotics, or fecal microbiota transplantation have been tested with promising results . Thus, quercetin, a flavonoid with high antioxidant capacity and strong anti‐inflammatory properties, has shown a potential prebiotic effect modulating gut microbiota composition in animal models of obesity and NAFLD .…”

The Regulation of Host Intestinal Microbiota by Polyphenols in the Development and Prevention of Chronic Kidney Disease

“…Polyphenol-rich cocoa decreased the Firmicutes/ Bacteriodetes ratio and increased Faecalibacterium prausnitzii levels in pigs (59). The countering of intestinal microbiota dysbiosis in rats fed with an HFD and sucrose diet inhibited body weight gain, decreased serum insulin, reduced the Firmicutes/Bacteriodetes ratio, and restricted bacterium production associated with lifestyle-associated obesity (60,61). A relative increase in the abundance of bactericides in subjects drinking red wine polyphenols has also been reported (62).…”