Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury

Abstract

Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endotoxin absorption. Probiotic bacteria have been shown to promote intestinal epithelial integrity and protect barrier function in inflammatory bowel disease (IBD) and in ALD. Although it is highly possible that some common molecules secreted by probiotics contribute to this action in IBD, the effect of probiotic culture supernatant has not yet been studied in ALD. We examined the effects of Lactobacillus rhamnosus GG culture supernatant (LGG-s) on the acute alcohol-induced intestinal integrity and liver injury in a mouse model. Mice on standard chow diet were supplemented with supernatant from LGG culture (10(9) colony-forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body wt was administered via gavage. Intestinal permeability was measured by FITC-FD-4 ex vivo. Alcohol-induced liver injury was examined by measuring the activity of alanine aminotransferase (ALT) in plasma, and liver steatosis was evaluated by triglyceride content and Oil Red O staining of the liver sections. LGG-s pretreatment restored alcohol-induced reduction in ileum mRNA levels of claudin-1, intestine trefoil factor (ITF), P-glycoprotein (P-gp), and cathelin-related antimicrobial peptide (CRAMP), which play important roles on intestinal barrier integrity. As a result, LGG-s pretreatment significantly inhibited the alcohol-induced intestinal permeability, endotoxemia and subsequently liver injury. Interestingly, LGG-s pretreatment increased ileum mRNA expression of hypoxia-inducible factor (HIF)-2α, an important transcription factor of ITF, P-gp, and CRAMP. These results suggest that LGG-s ameliorates the acute alcohol-induced liver injury by promoting HIF signaling, leading to the suppression of alcohol-induced increased intestinal permeability and endotoxemia. The use of bacteria-free LGG culture supernatant provides a novel strategy for prevention of acute alcohol-induced liver injury.

Supplementation with Lactobacillus rhamnosus SP1 normalises skin expression of genes implicated in insulin signalling and improves adult acne

“…Notably, LGG has been shown to improve gut permeability (Wang et al, 2012;Sindhu et al, 2014). In this study, modulation of gut microbiota and permeability by LGG (with an associated reduction in endotoxemia and TLR-4 activation) may have lowered FOXO1 skin expression.…”

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

“…In addition, L. rhamnosus treatment modulates the immune system (Forsythe et al, 2012;Karimi et al, 2009;Kozakova et al, 2016;Ma et al, 2004), intestinal motility , gut barrier function (Patel et al, 2012;Wang et al, 2012) and enteric nervous system (Kamiya et al, 2006;Ma et al, 2009). Taken together, these preclinical studies identify L. rhamnosus as a candidate psychobiotic with the one of the most comprehensive behavioural, physiological and neurobiological profiles.…”

Puerarin Ameliorates Experimental Alcoholic Liver Injury by Inhibition of Endotoxin Gut Leakage, Kupffer Cell Activation, and Endotoxin Receptors Expression

“…It also has been observed the alcoholic liver injury in rats is associated with increased levels of plasma endotoxin (Mathurin et al, 2000;Tsukamoto et al, 2008). Furthermore, administration of antibiotics (Adachi et al, 1995) and probiotic bacteria (Wang et al, 2012) to rodents reduces the growth of Gram-negative bacteria in the intestinal lumen and prevents EtOH-induced endotoxemia and liver injury. It has been suggested that in ALD the endotoxin levels at specific locations such as in portal blood might be more important than the levels in systemic plasma (Lambert et al, 2003).…”