Lactobacillus lactis and Pediococcus pentosaceus‐driven reprogramming of gut microbiome and metabolome ameliorates the progression of non‐alcoholic fatty liver disease

Abstract

Background Although microbioa‐based therapies have shown putative effects on the treatment of non‐alcoholic fatty liver disease (NAFLD), it is not clear how microbiota‐derived metabolites contribute to the prevention of NAFLD. We explored the metabolomic signature of Lactobacillus lactis and Pediococcus pentosaceus in NAFLD mice and its association in NAFLD patients. Methods We used Western diet‐induced NAFLD mice, and L. lactis and P. pentosaceus were administered to animals in the drinking water at a concentration of 10 9 CFU/g for 8 weeks. NAFLD severity was determined based on liver/body weight, pathology and biochemistry markers. Caecal samples were collected for the metagenomics by 16S rRNA sequencing. Metabolite profiles were obtained from caecum, liver and serum. Human stool samples (healthy control [ n = 22] and NAFLD patients [ n = 23]) were collected to investigate clinical reproducibility for microbiota‐derived metabolites signature and metabolomics biomarker. Results L. lactis and P. pentosaceus supplementation effectively normalized weight ratio, NAFLD activity score, biochemical markers, cytokines and gut‐tight junction. While faecal microbiota varied according to the different treatments, key metabolic features including short chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites were analogously restored by both probiotic supplementations. The protective effects of indole compounds were validated with in vitro and in vivo models, including anti‐inflammatory effects. The metabolomic signatures were replicated in NAFLD patients, accompanied by the comparable levels of Firmicutes / Bacteroidetes ratio, which was significantly higher (4.3) compared with control (0.6). Besides, the consequent biomarker panel with six stool metabolites (indole, BAs, and SCFAs) showed 0.922 (area under the curve) in the diagnosis of NAFLD. Conclusions NAFLD progression was robustly associated with metabolic dys‐regulations in the SCFAs, bile acid and indole compounds, and NAFLD can be accurately diagnosed using the metabolites. L. lactis and P. pentosaceus ameliorate NAFLD progression by modulating gut metagenomic and metabolic environment, particularly tryptophan pathway, of the gut‐liver axis.

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

“… 493 Lactobacillus lactis and Pediococcus pentosaceus also restored metabolite dysregulation in the gut of western diet‐induced NAFLD mice. 494 …”

Analysis of Gut Microbiota Signature and Microbe-Disease Progression Associations in Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Concurrent Chemoradiotherapy

“…A study focusing on the role of the microbiome in obesity and diabetes in humans and rodents revealed significant differences of gut microbiota between lean and obese subjects, most notably an increased F/B ratio in obesity subjects ( Ley et al., 2006 ). Analysis of non-alcoholic fatty liver disease patients also showed an elevated F/B ratio compared with healthy control ( Yu et al., 2021 ). In addition, higher risk of breast cancer recurrence was reported to be associated with lower F/B ratio ( Okubo et al., 2020 ).…”

Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine

“…Studies have demonstrated that the gut microbiota is involved in NAFLD disease progression with complex roles ( Brandl and Schnabl, 2017 ). Yu et al (2021) used GC-MS, LC-MS and other metabolomics analysis methods to detect the cecal metabolic profile of NAFLD mice and the fecal metabolic profile of NAFLD patients. They found that compared with normal controls, NAFLD patients and NAFLD mice had intestinal metabolites and microbial communities were significantly changed.…”