Ability of prebiotic polysaccharides to activate a HIF1α-antimicrobial peptide axis determines liver injury risk in zebrafish

Abstract

Natural polysaccharides have received much attention for their ability to ameliorate hepatic steatosis induced by high-fat diet. However, the potential risks of their use have been less investigated. Here, we show that the exopolysaccharides (EPS) from Lactobacillus rhamnosus GG (LGG) and L. casei BL23 reduce hepatic steatosis in zebrafish fed a high-fat diet, while BL23 EPS, but not LGG EPS, induce liver inflammation and injury. This is due to the fact that BL23 EPS induces gut microbial dysbiosis, while LGG EPS promotes microbial homeostasis. We find that LGG EPS, but not BL23 EPS, can directly activate intestinal HIF1α, and increased HIF1α boosts local antimicrobial peptide expression to facilitate microbial homeostasis, explaining the distinct compositions of LGG EPS- and BL23 EPS-associated microbiota. Finally, we find that liver injury risk is not confined to Lactobacillus -derived EPS but extends to other types of commonly used natural polysaccharides, depending on their HIF1α activation efficiency.

Gut microbiota dynamics in carnivorous European seabass (Dicentrarchus labrax) fed plant-based diets

“…Galactose is the predominant sugar residue in SBM, arabinose in RSM, and xylose in SFM 83 . As recently described in zebrafish 84 , and extensively in mice and humans (reviewed in 85 ), different polysaccharides, including different NSP, have different effects on gut microbiota. Some contribute to the maintenance of gut microbial homeostasis, while others potentiate gut dysbiosis.…”

“…Some contribute to the maintenance of gut microbial homeostasis, while others potentiate gut dysbiosis. This microbiota modulation is dependent on the polysaccharide structure, its fermentation by the gut bacteria and its direct interaction with the gut epithelium and mucus, which ultimately might result in physiological and inflammatory imbalances [83][84][85] . Although carbohydrates-metabolism has been exhaustively studied in different microorganisms, including gut ones, and there is enough genomic information (both from individual microorganisms and metagenomics studies) confirming that gut microorganisms possess the necessary enzymatic tools to metabolize different NSPs, it is not known which of these organisms are indeed capable of such metabolizing jobs within the complex context of natural gut communities and if metabolic pathways, capabilities and preferences determined in vitro will be replicated inside the gut.…”

Short-Chain Fatty Acids Promote Intracellular Bactericidal Activity in Head Kidney Macrophages From Turbot (Scophthalmus maximus L.) via Hypoxia Inducible Factor-1α

“…Previous study has illustrated that the activation of HIF-1 α resulted in the elevated expression of cathelicidins in order to inhibit gastrointestinal colonization of fungi ( 15 ). Recently, it was reported that the activation of intestinal HIF-1 α boosted local AMP expression to facilitate microbial homeostasis in zebrafish ( 51 ). Nevertheless, our result showed that the gene expression of turbot hepcidin in HKMs was not increased by SCFA treatment (data not shown).…”

Commensal bacteria‐immunity crosstalk shapes mucosal homeostasis in teleost fish

“…17,18 Although bacterial composition may be altered by endogenous and exogenous factors such as diet, age, genetics, sex, captivity, tissue and environmental conditions, the dominant species in specific organs are often consistent. [19][20][21][22][23][24][25] Previous studies have demonstrated that the microbial communities of teleost fish vary depending on the tissues they inhabit. 11,18,26 Additionally, new discoveries have been made in recent years regarding fish mucosal microbiota.…”