Modulation of the Microbiome–Fat–Liver Axis by Lactic Acid Bacteria: A Potential Alleviated Role in High-Fat-Diet-Induced Obese Mice

Abstract

The major characteristics of obesity are abnormal lipid metabolism, chronic inflammation, and imbalanced gut microbiota. It has been reported that lactic acid bacteria (LAB) possess potential for alleviating obesity, considering which the strainspecific functions and diverse mechanisms and the roles and mechanisms of various LAB are worthy of investigation. This study aimed to validate and investigate the alleviating effects and underlying mechanisms of three LAB strains, Lactiplantibacillus plantarum NCUH001046 (LP), Limosilactobacillus reuteri NCUH064003, and Limosilactobacillus fermentum NCUH003068 (LF), in high-fatdiet-induced obese mice. The findings demonstrated that the three strains, particularly LP, suppressed body weight gain and fat deposition; ameliorated lipid disorders, liver and adipocyte morphology, and chronic low-grade inflammation; and reduced lipid synthesis via activating the adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling pathway. In addition, LP and LF decreased the enrichment of bacteria positively correlated with obesity, like Mucispirillum, Olsenella, and Streptococcus, but facilitated the growth of beneficial bacteria negatively correlated with obesity, like Roseburia, Coprococcus, and Bacteroides, along with increasing the short-chain fatty acid levels. It is deduced that the underlying alleviating mechanism of LP was to modulate the hepatic AMPK signaling pathway and gut microbiota by the microbiome−fat−liver axis to alleviate obesity development. In conclusion, as a diet supplement, LP has promising potential in obesity prevention and treatment.

Probiotic-fermented tomato with hepatic lipid metabolism modulation effects: analysis of physicochemical properties, bioactivities, and potential bioactive compounds

“…Western blot analysis was conducted according to our previous study 17 to analyze the relative expression of hepatic proteins by using the primary antibody of adenosine 5′-monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), acetyl-CoA carboxylase (ACC, Abcam, Cambridge, UK), phosphorylated ACC (p-ACC), carnitine palmitoyltransferase-1 (CPT-1), fatty acid synthase (FAS), peroxisome proliferator-activated receptor α (PPARα), and β-actin (Beyotime, Shanghai, China). All primary antibodies were purchased from Proteintech Group, Inc. (Rosemont, USA) unless otherwise noted.…”

“…In our previous study, Lactiplantibacillus plantarum NCUH001046 (LP) and its fermented tomato (FT) were found to possess alleviating effects in high-fat diet-induced obese mice, including lowering body weight gain, ameliorating dyslipidemia, and modulating the gut microbiota. 17,18 However, the modulation effects of FT on hepatic lipid metabolism were not clear. Furthermore, FT, especially live probiotic-fermented tomatoes (LFT), exhibited enhanced obesity-alleviating effects compared to unfermented tomatoes (UFT), which may be partially attributed to the live LP in it.…”

Gut microbiota and metabolite interface-mediated hepatic inflammation

“…The gut-liver axis, a physiological crosstalk between the gut and liver via immunological and metabolic signals, can be regulated by dietary, genetic, epigenetic, and environmental factors [5,6] . Most metabolic diseases, such as obesity [7,8] , type 2 diabetes [9,10] , and cardiovascular diseases (CVDs) [11,12] , are associated with a disruption of the balance of gut microbiota (dysbiosis) leading to changes in intestinal permeability and systemic inflammation [13] . Accumulating evidence also shows that gut microbiota dysbiosis can specifically impact hepatic inflammation and metabolism in chronic liver diseases at different stages [14,15] .…”