Abstract
BackgroundPre-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.MethodsLactate 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.ResultsPretreatment 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.ConclusionLactate 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.
Highlights
Pre-administration of probiotic Lactobacilli attenuates ethanol-induced gastric mucosal injury (GMI)
Lactate reduced the severity of ethanol-induced GMI in mice Extensive hemorrhagic injuries of the gastric mucosa were observed in mice that have been orally given absolute ethanol at 0.1 mL/ g (Fig. 1a)
Lactate mitigated excessive inflammation encountered in GMI Anti-inflammatory effect of lactate was determined by examining the level of pro-inflammatory cytokines IL1β, Tumor necrosis factor (TNF)-α and IL-6 in homogenized gastric tissues
Summary
Pre-administration of probiotic Lactobacilli attenuates ethanol-induced gastric mucosal injury (GMI). Gastric mucosal injury (GMI) is a common precancerous condition related to the high incidence of gastric cancer in many Asian countries, including China [1,2,3,4]. It is known that gastric mucosal injury is associated with elevated local inflammation in the gastric mucosa, with inflammatory cytokines such as IL-1β, TNF-α and IL-6 all being overexpressed [6, 7]. Apoptosis is a key mechanism driving the pathogenesis of gastric mucosal injury [8]. Numerous in vivo studies have reported that many genera of probiotic Lactobacilli had protective effects on the gastric mucosa; the underlying mechanisms, remain to be fully elucidated [11,12,13,14,15,16]. Hoque et al (2014) and Ranganathan et al (2018) both found that lactate was able to attenuate intestinal inflammation via endothelial lactate-receptor GPR81 signaling pathway [19, 20]
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