Lactobacillus acidophilus LA5 improves saturated fat-induced obesity mouse model through the enhanced intestinal Akkermansia muciniphila

Thunnicha Ondee,Chitrasak Kullapanich,Peerapat Visitchanakun,Suthicha Kanacharoen,Lampet Wongsaroj,Krit Pongpirul,Natharin Ngamwongsatit,Naraporn Somboonna,Wilasinee Saisorn,Asada Leelahavanichkul,Sarn Settachaimongkon

doi:10.1038/s41598-021-85449-2

Abstract

Obesity, a major healthcare problem worldwide, induces metabolic endotoxemia through the gut translocation of lipopolysaccharides (LPS), a major cell wall component of Gram-negative bacteria, causing a chronic inflammatory state. A combination of several probiotics including Lactobacillus acidophilus 5 (LA5), a potent lactic acid-producing bacterium, has previously been shown to attenuate obesity. However, data on the correlation between a single administration of LA5 versus microbiota alteration might be helpful for the probiotic adjustment. LA5 was administered daily together with a high-fat diet (HFD) for 8 weeks in mice. Furthermore, the condition media of LA5 was also tested in a hepatocyte cell-line (HepG2 cells). Accordingly, LA5 attenuated obesity in mice as demonstrated by weight reduction, regional fat accumulation, lipidemia, liver injury (liver weight, lipid compositions, and liver enzyme), gut permeability defect, endotoxemia, and serum cytokines. Unsurprisingly, LA5 improved these parameters and acidified fecal pH leads to the attenuation of fecal dysbiosis. The fecal microbiome analysis in obese mice with or without LA5 indicated; (i) decreased Bacteroidetes (Gram-negative anaerobes that predominate in non-healthy conditions), (ii) reduced total fecal Gram-negative bacterial burdens (the sources of gut LPS), (iii) enhanced Firmicutes (Gram-positive bacteria with potential benefits) and (iv) increased Verrucomycobia, especially Akkermansia muciniphila, a bacterium with the anti-obesity property. With LA5 administration, A. muciniphila in the colon were more than 2,000 folds higher than the regular diet mice as determined by 16S rRNA. Besides, LA5 produced anti-inflammatory molecules with a similar molecular weight to LPS that reduced cytokine production in LPS-activated HepG2 cells. In conclusion, LA5 attenuated obesity through (i) gut dysbiosis attenuation, partly through the promotion of A. muciniphila (probiotics with the difficulty in preparation processes), (ii) reduced endotoxemia, and (iii) possibly decreased liver injury by producing the anti-inflammatory molecules.

Highlights

Obesity, a major healthcare problem w orldwide[1], is associated with diabetes, dyslipidemia, and cardiovascular disease that leads to several major complications in critically-ill p atients[1]
Beneficial molecules secreted by probiotics may be delivered alongside harmful pathogen-associated molecular patterns (PAMPs) into the circulatory system during gut leakage
Because (i) Gram-negative bacteria in the gut is a source of endotoxin (LPS)[7], (ii) obesity enhances endotoxemia from gut translocation[25] and (iii) molecules from gut translocation is possibly directly transported to the liver through portal v eins[7], the reduced serum endotoxin in Lactobacillus acidophilus 5 (LA5) administered-obese mice implies the improved gut dysbiosis

Summary

Introduction

A major healthcare problem w orldwide[1], is associated with diabetes, dyslipidemia, and cardiovascular disease that leads to several major complications in critically-ill p atients[1]. Obesity-induced chronic inflammation leads to atherosclerosis which is a key vascular complication in obesity[2]. Obesity and a high-fat diet (HFD) cause gut d ysbiosis[8] (an alteration of organisms in the intestine9), enhancing gut-mucosal injury enough to allow the direct translocation of high molecular weight (MW) molecules, such as LPS, into the liver and circulatory system[10,11]. Beneficial molecules secreted by probiotics may be delivered alongside harmful PAMPs into the circulatory system during gut leakage. (i) Lactobacillus spp. attenuates gut dysbiosis in several animal models[20,21,22,23,24,25] and (ii) Lactobacillus acidophilus (LA), in combination with other probiotics, attenuates hyperlipidemia, overweight and obesity-induced hepatitis (steatohepatitis)[12,26,27,28,29], the effect of LA alone upon obesity and steatohepatitis is still unclear. Lactobacillus acidophilus LA5 (LA5) was used as a single strain probiotic in a mouse model with saturated fat induced-obesity and was tested in the hepatocyte cell-line experiments

Methods

Results

Conclusion