Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

Abstract

The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a "low bacterial richness" may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier ("leaky gut"), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.

Calcium Reduces Liver Injury in Mice on a High-Fat Diet: Alterations in Microbial and Bile Acid Profiles

“…Additionally, in a subset of individuals, chronic NASH leads to hepatocellular carcinoma (HCC) [9–12]. NAFLD is rapidly becoming the most common cause of chronic liver injury in industrialized countries, in parallel with the increased consumption of a high fat, “Western-style” diet (HFWD) [3,4]. Dietary caloric restriction to reduce steatosis is a mainstay of NAFLD prevention, but its efficacy is hampered by poor compliance and potentially by early life metabolic and gut microbial alterations that have prolonged inhibitory effects on weight loss [4].…”

Oral Glutamine Supplementation Protects Female Mice from Nonalcoholic Steatohepatitis

“…Here, through feeding a WSD, early metabolic as well as molecular changes associated with the development of NASH (e.g., steatosis, inflammation, and insulin resistance) were induced in mice. Chronic intakes of this WSD promote pathological changes in the liver as well as at the level of intestine, which are also found in many humans with early NASH [for an overview of alterations, see also (20)(21)(22)]. Of course, despite many similarities with the human situation, it needs to be emphasized that the chronic intake in mice of a pair-fed liquid diet containing 50% wt:wt fructose and 25 E% fat with 0.16% wt:wt cholesterol does not resemble all alterations found in humans with NAFLD (e.g., genetic predisposition, lack of physical inactivity).…”

Can NASH lipidome provide insight into the pathogenesis of obesity-related non-alcoholic fatty liver disease?

“…The authors concluded that visceral adipose contributing to overall lipidome was secondary to that of other sources of the drainage into the hepatic portal system, for example, the gut. While this is by no means a novel suggestion in the field of NASH [5][6][7], the exact mechanism of this contribution has yet to be demonstrated.…”