A Keystone Gut Bacterium Christensenella minuta-A Potential Biotherapeutic Agent for Obesity and Associated Metabolic Diseases

Abstract

A new next-generation probiotic, Christensenella minuta was first discovered in 2012 from healthy human stool and described under the phylum Firmicutes. C. minuta is a subdominant commensal bacterium with highly heritable properties that exhibits mutual interactions with other heritable microbiomes, and its relative abundance is positively correlated with the lean host phenotype associated with a low BMI index. It has been the subject of numerous studies, owing to its potential health benefits. This article reviews the evidence from various studies of C. minuta interventions using animal models for managing metabolic diseases, such as obesity, inflammatory bowel disease, and type 2 diabetes, characterized by gut microbiota dysbiosis and disruption of host metabolism. Notably, more studies have presented the complex interaction between C. minuta and host metabolism when it comes to metabolic health. Therefore, C. minuta could be a potential candidate for innovative microbiome-based biotherapy via fecal microbiota transplantation or oral administration. However, the detailed underlying mechanism of action requires further investigation.

Keywords: Christensenella minuta; inflammatory bowel disease; metabolic diseases; next-generation probiotic; obesity.

Figure 1

Mechanisms underlying the anti-obesity role of Christensenella minuta. (1) Modulation of gut microbiota—C. minuta renormalizes gut microbiome composition by balancing the ratio between Firmicutes/Bacteroidetes. (2) Production of short-chain fatty acids—C. minuta enhances the browning of white adipose tissues, which promotes lipolysis. (3) Modulation of lipid metabolism—C. minuta promotes thermogenesis and reduces hepatic lipid accumulation in brown adipose tissues. (4) Regulation of gut epithelial integrity—C. minuta enhances intestinal barrier integrity by regulating the tight junction assembly through the activation of AMP-activated protein kinase (AMPK). (5) Modulation of bile acid metabolism—C. minuta shows a high-level expression of bile salt hydrolases (BSH), resulting in the stimulation of fatty acid oxidation while inhibiting triglyceride and hepatic fatty acid production.