2 | Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 research update Role of Gut Microbiome Dysbiosis in the Pathogenesis of Nonalcoholic Fatty Liver Disease The diverse gut microbiome population is crucial for maintaining the integrity of the mucosal barrier function, absorption of nutrients, and maintaining energy balance. The predominant gut microbiome population comprises the Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia. Of these, Firmicutes and Bacteroidetes account for 90% of the gut microbiome. The liver has an intricate interaction with the gut, wherein it receives more than two-thirds of blood from the gastrointestinal tract through the portal system. The interaction between the gut and the liver occurs through hormones, inflammatory mediators, and products of digestion and absorption. Any disturbance/disruption in this communication and feedback loops between the gastrointestinal tract and the liver can affect the mucosal integrity, immunologic function, and metabolism, and hence, can lead to chronic liver diseases such as nonalcoholic fatty liver disease (NAFLD). The Gut–Liver Axis NAFLD, involving a wide range of liver disorders that range from hepatic steatosis to nonalcoholic steatohepatitis, is characterized histologically by hepatocyte injury, inflammation, and varying degrees of fibrosis. Accumulating preclinical and clinical evidence suggests that the pathogenesis of NAFLD is delicately orchestrated by the gut microbiome. Gut dysbiosis serves as an important determinant for the development and progression of NAFLD. Research on NAFLD animal models shows a variety of changes in the relative abundances of Bacteroidetes, Firmicutes, and Ruminococcus. The composition of the gut microbiome is also observed to vary throughout different stages of NAFLD. Compositional Alteration in the Gut Microbiome in NAFLD: Research Findings A recent comprehensive review and meta-analysis on compositional alterations in the gut microbiome in patients with NAFLD found a characteristic compositional pattern and revealed the following findings: 1. The fecal microbiome constituted an increased number of Prevotella and species of Escherichia and Streptococcus, and fewer Coprococcus, Faecalibacterium, and Ruminococcus species. 2. The BMI may contribute to the change in the percentage of distribution (abundance) of Faecalibacterium species and Prevotella in patients with NAFLD, compared with healthy controls. 3. The change in the percentage of distribution of Streptococcus and Faecalibacterium species indicates increased systemic inflammation, which is a favorable index of progression of the NAFLD pathology. Pathomechanisms in the Dysregulation of the Gut– Liver Axis The following are the pathologic factors that dysregulate the equilibrium of the gut–liver axis and its relationship with the onset of NAFLD: Intestinal permeability Bacterial overgrowth in the intestine can affect the functionality of the tight
RkJQdWJsaXNoZXIy MjAwNDg=