Lactate as a metabolite from probiotic Lactobacilli mitigates ethanol-induced gastric mucosal injury: an in vivo study

Abstract

Background Pre-administration of probiotic Lactobacilli attenuates ethanol-induced gastric mucosal injury (GMI). The underpinning mechanisms remain to be elucidated. We speculated that lactate, the main metabolite of Lactobacillus that can be safely used as a common food additive, mediated the gastroprotective effect. This study aimed to gain experimental evidence to support our hypothesis and to shed lights on its underlying mechanisms. Methods Lactate was orally administrated to mice at different doses 30 min prior to the induction of GMI. Gastric tissue samples were collected and underwent histopathological and immunohistochemical assessments, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction (qPCR) and western blot analyses. Results Pretreatment with lactate at 1–3 g/kg significantly curtailed the severity of ethanol-induced GMI, as shown by morphological and histopathological examinations of gastric tissue samples. Significantly lower level of cytokines indicative of local inflammation were found in mice receiving lactate treatment prior to ethanol administration. Western-blot, immunohistochemical analysis and qPCR suggested that gastroprotective properties of lactate were mediated by its modulatory effects on the expression of the apoptosis regulator gene Bax, the apoptotic executive protein gene Casp3, and genes critical for gastric mucosal integrity, including those encoding tight junction proteins Occludin, Claudin-1, Claudin-5, and that for lactate receptor GPR81. Conclusion Lactate mitigates ethanol-induced GMI by curtailing local gastric inflammatory response, down-regulating the expression of the apoptosis regulator and executor genes Bax and Casp3, and up-regulating the expression of genes encoding tight junction proteins Occludin, Claudin-1, and Claudin-5 and the lactate receptor GPR81.

Postbiotics, Metabolic Signaling, and Cancer

“…The endogenously produced lactate in the established tumors has been identified as a driver of angiogenesis, immune evasion, metastasis, and resistance to therapy [106]. On the other hand, lactate delivered by postbiotic supplementation may serve as an inhibitor of carcinogenesis through the maintenance of the epithelial integrity and downregulation of the tissue inflammation [11,[107][108][109][110][111].…”

Influence of Sports Training in Foothills on the Professional Athlete’s Immunity

“…For decades, secondary immunosuppression has been considered a natural condition in athletes at the peak of their form [ 13 , 14 , 15 ]. New data may provide a different perspective on this process, as the functional state of cellular immunity is closely related to athletes’ environmental conditions and depends not only on the macrocycle period but also on the training camp location.…”

“…Some authors have noted the possibility of cytotoxic effects resulting from intense physical activity at its peak without proper nutrient and metabolic correction, which are mainly mediated by different types of T-cells and is of fundamental importance in the immunological control of the development of immunosuppressive stress in the body of athletes [ 13 , 14 , 15 , 32 , 33 ].…”

3-phenyllactic acid promotes healthspan through SKN-1/ATFS-1-mediated mitochondrial activation and stress resilience

“…Furthermore, recent in vivo studies comparing lactate and glucose metabolism have shown that lactate predominates in feeding the TCA cycle, even in tumors 45 . Notably, given its safety as a common food additive, lactate supplementation has demonstrated various clinical health benefits, including the mitigation of ethanol-induced gastric mucosal damage, the prevention of inflammatory bowel disease, and the development of intestinal epithelium as mucosal delivery vehicles [46][47][48] . These studies collectively highlight the potential impact of lactate and its metabolites on energy metabolism and healthspan extension at the organismal level.…”