Propionic Acid, Induced in Gut by an Inulin Diet, Suppresses Inflammation and Ameliorates Liver Ischemia and Reperfusion Injury in Mice

Abstract

Liver ischemia and reperfusion injury (IRI) is one of the obstacles in liver surgery such as liver resection and transplantation. In this study, we investigated the preventive effect on mouse liver IRI by feeding mice with inulin, which is a heterogeneous blend of indigestible fructose polymer. Mice were fed either a control ordinary diet (CD) or an inulin diet (ID) containing 5% inulin in the CD, for 14 days before the ischemia and reperfusion (IR) maneuver. IR induced-liver damages were significantly ameliorated in the ID group, compared with those in the CD group. Feeding mice with an ID, but not a CD, elevated levels of Bacteroidetes among gut microbiota, and especially increased Bacteroides acidifaciens in mouse feces, which resulted in significant elevation of short-chain fatty acids (SCFAs) in the portal vein of mice. Among SCFAs, propionic acid (PA) was most significantly increased. The microbial gene functions related to PA biosynthesis were much higher in the fecal microbiome of the ID group compared to the CD. However, the action of PA on liver IRI has not been yet clarified. Direct intraperitoneal administration of PA alone prior to the ischemia strongly suppressed liver cell damages as well as inflammatory responses caused by liver IR. Furthermore, PA suppressed the secretion of inflammatory cytokines from peritoneal macrophages stimulated in vitro through TLR-4 with high-mobility group box 1 protein (HMGB-1), known to be released from apoptotic liver cells during the IR insult. The present study shows that PA may play a key role in the inulin-induced amelioration of mouse liver IRI.

Polygonatum kingianum Polysaccharides Enhance the Preventive Efficacy of Heat-Inactivated Limosilactobacillus reuteri WX-94 against High-Fat-High-Sucrose-Induced Liver Injury and Gut Dysbacteriosis

“…Besides, succinic acid, kojic acid, and propionic acid were highly abundant in the pasteurized PKP–L. reuteri, which are reported to possess a variety of pharmacological effects, including cardioprotective, anti-inflammatory, and antibacterial. ,− Recent studies highlighted the beneficial impacts of propionic acid on ameliorating liver dysfunctions via activation of the APN-AMPK-PPARα signaling pathway, thereby inhibiting fatty acid de novo synthesis and promoting β-oxidation. − Zhou et al found that phenyllactic acid derived from Lactobacillus effectively regulated microbiota composition, improved SCFA production, and reduced inflammatory responses. In addition, the important roles of indole derivatives, indole-3-carbinol, and indole-lactic acid predominately produced by L.…”

Hormonal drugs: Influence on growth, biofilm formation, and adherence of selected gut microbiota

“…The effect of the tested drug compounds in this study on SCFAs production was variable and mostly independent of their effect on bacterial growth, in contrast to earlier studies’ results that a change in abundance of gut bacteria owing to drug usage was correlated to a similar effect on SCFAs production ( Hojo et al., 2018 ). Notably, numerous studies reveal that Bacteroidetes are the main producers of propionate in the human gut ( Salonen et al., 2014 ; Aguirre et al., 2016 ) and this SCFA is known for its ability to suppress inflammation and the increase in its level is associated with cognitive decline in elderly ( Kawasoe et al., 2022 ; Neuffer et al., 2022 ) while low level of propionic acid and acetate was linked to autism( Tetel et al., 2018 ). Progesterone and L-thryoxine reduced the production of propionic acid by B. fragilis .…”

Crosstalk between liver macrophages and gut microbiota: An important component of inflammation-associated liver diseases

“…420 ) was found to alleviate S100-induced experimental autoimmune hepatitis (EAH) by modulating RIP3 signaling of hepatic macrophages ( Zhang et al, 2020 ). In addition, an inulin diet was shown to ameliorate IR-induced ALI, accompanied by significant increases in the abundance of Bacteroides acidifaciens in feces and its SCFAs, especially propionic acid (PA), in the portal vein ( Kawasoe et al, 2022 ). Furthermore, PA alone was sufficient to inhibit macrophages activated through HMGB-1/TLR4 signaling in vitro ( Kawasoe et al, 2022 ).…”

“…In addition, an inulin diet was shown to ameliorate IR-induced ALI, accompanied by significant increases in the abundance of Bacteroides acidifaciens in feces and its SCFAs, especially propionic acid (PA), in the portal vein ( Kawasoe et al, 2022 ). Furthermore, PA alone was sufficient to inhibit macrophages activated through HMGB-1/TLR4 signaling in vitro ( Kawasoe et al, 2022 ). The gut microbiota metabolite 3,4-dihydroxyphenylpropionic acid was shown to play a similar role in IR-induced ALI ( Li R. et al, 2022 ).…”

“…through HMGB-1/TLR4 signaling. Ameliorates IR induced-ALI with increased Bacteroides acidifaciens and short-chain fatty acids (SCFAs) especially propionic acidKawasoe et al (2022) Reduces macrophage and its TLR4 signaling in liver. Ameliorates inflammation by hindering Nod-Like Receptor Protein 3 Inflammasome as well as NF-κB signaling in NAFLD Bao et al (2020).…”