Surface-Displayed Amuc_1100 From Akkermansia muciniphila on Lactococcus lactis ZHY1 Improves Hepatic Steatosis and Intestinal Health in High-Fat-Fed Zebrafish

Abstract

Fatty liver and intestinal barrier damage were widespread in most farmed fish, which severely restrict the development of aquaculture. Therefore, there was an urgent need to develop green feed additives to maintain host liver and intestinal health. In this study, a probiotic pili-like protein, Amuc_1100 (AM protein), was anchored to the surface of Lactococcus lactis ZHY1, and the effects of the recombinant bacteria AM-ZHY1 on liver fat accumulation and intestinal health were evaluated. Zebrafish were fed a basal diet, high-fat diet, and high-fat diet with AM-ZHY1 (108 cfu/g) or control bacteria ZHY1 for 4 weeks. Treatment with AM-ZHY1 significantly reduced hepatic steatosis in zebrafish. Quantitative PCR (qPCR) detection showed that the expression of the lipogenesis [peroxisome-proliferator-activated receptors (PPARγ), sterol regulatory element-binding proteins-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1)] and lipid transport genes (CD36 and FABP6) in the liver were significantly downregulated (p < 0.05), indicating that AM-ZHY1 could reduce liver fat accumulation by inhibiting lipid synthesis and absorption. Moreover, supplementing AM-ZHY1 to a high-fat diet could significantly reduce serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, indicating that liver injury caused by high-fat diets was improved. The expression of tumor necrosis factor (TNF)-a and interleukin (IL)-6 in the liver decreased significantly (p < 0.05), while IL-1β and IL-10 did not change significantly in the AM-ZHY1 group. Compared to the high-fat diet-fed group, the AM-ZHY1 group, but not the ZHY1 group, significantly increased the expression of intestinal tight junction (TJ) proteins (TJP1a, claudina, claudin7, claudin7b, claudin11a, claudin12, and claudin15a; p < 0.05). Compared to the high-fat diet group, the Proteobacteria and Fusobacteria were significantly reduced and increased in the AM-ZHY1 group, respectively. In conclusion, the recombinant bacteria AM-ZHY1 has the capacity to maintain intestinal health by protecting intestinal integrity and improving intestinal flora structure and improving fatty liver disease by inhibiting lipid synthesis and absorption. This study will lay a foundation for the application of AM protein in improving abnormal fat deposition and restoring the intestinal barrier in fish.

Fructose Stimulated Colonic Arginine and Proline Metabolism Dysbiosis, Altered Microbiota and Aggravated Intestinal Barrier Dysfunction in DSS-Induced Colitis Rats

“…Probiotics including Adlercreutzia , Leuconostoc , Lactococcus and Oscillospira were significantly reduced in the fructose intake group, while some bacteria associated with induced inflammation and diseases ( Allobaculum and Holdemania , Figure 4 D) were observed to be enriched in fructose intake group. Adlercreutzia [ 27 ], Leuconoxtoc [ 31 ], Lactococcus [ 32 ] and Oscillospira [ 42 ] were proven as probiotic or had a positive correlation with human/animal health. It is hinted that even though both sucrose and fructose changed gut bacteria in experimental colitis rats, fructose levels tended to change for the worse situation.…”

Pediococcus pentosaceus PR-1 modulates high-fat-died-induced alterations in gut microbiota, inflammation, and lipid metabolism in zebrafish

“…Intestinal TJ proteins, including occludin, claudin, and ZO-1 play an important role in maintaining gut permeability and barrier function ( 48 ). Previous studies reported that as the TJ expression levels decreased induced by HFD, the gut permeability increased, which lead to increased level of serum endotoxemia and impaired immune response ( 42 , 48 ). We investigated whether probiotic P. pentosaceus PR-1 could improve gut barrier function in HFD-fed zebrafish.…”

“…Several studies have found zebrafish serve as a useful animal model of human HFD-induced obesity for research into the alterations of gut microbiota community and inflammation driven by HFD due to its similarity of organs to humans, the availability of a complete genome sequence, and its highly conserved physiological pathways (2,(38)(39)(40)(41)(42)(43). Although zebrafish is dominated by Proteobacteria, mice and human are dominated by Firmicutes and Bacteroidetes, the response to microbiota colonization are similar (44).…”

Microbiome-based interventions to modulate gut ecology and the immune system

“…Cell line experiments have also shown that activation of TLR2 can increase the expression of tight junction proteins 232 , which may be the mechanism by which A. muciniphila improves barrier function (Fig. 2) 233 . In human trials, A. muciniphila Muc can improve barrier function, as shown by reduced plasma LPS levels, however this effect was only significant when pasteurised cells and not live cells were ingested 163 .…”