This study aims to systematically evaluate the safety of a novel L. plantarum LPJZ-658 explored on whole-genome sequence analysis, safety, and probiotic properties assessment. Whole genome sequencing results demonstrated that L. plantarum LPJZ-658 consists of 3.26 Mbp with a GC content of 44.83%. A total of 3254 putative ORFs were identified. Of note, a putative bile saline hydrolase (BSH) (identity 70.4%) was found in its genome. In addition, the secondary metabolites were analyzed, and one secondary metabolite gene cluster was predicted to consist of 51 genes, which verified its safety and probiotic properties at the genome level. Additionally, L. plantarum LPJZ-658 exhibited non-toxic and non-hemolytic activity and was susceptible to various tested antibiotics, indicating that L. plantarum LPJZ-658 was safe for consumption. Moreover, the probiotic properties tests confirm that L. plantarum LPJZ-658 also exhibits tolerance to acid and bile salts, preferably hydrophobicity and auto-aggregation, and excellent antimicrobial activity against both Gram-positive and Gram-negative gastrointestinal pathogens. In conclusion, this study confirmed the safety and probiotic properties of L. plantarum LPJZ-658, suggesting it can be used as a potential probiotic candidate for human and animal applications.

This study aimed to investigate the effects of L. plantarum LPJZ-658 on the production, meat quality, intestinal morphology, and cecal microbiota of broilers. White-feathered broilers (1 day old, n = 600) were randomly assigned to two groups and raised for six weeks. The individuals in the LPJZ-658 group were supplemented with 2.6 × 10⁹ cfu/g LPJZ-658. The growth performance, meat quality, intestinal epithelium morphology, and cecal microbiota were observed. The results showed that the average daily gain, average daily feed intake, and feed conversion ratio of broilers in the LPJZ-658 group were significantly improved. In addition, the LPJZ-658 groups had a higher thigh muscle (TM) yield, TM color, TM_pH24h, breast muscle (BM) pH_24h, and BM color_24h, while the BM cooking loss was significantly lower than the CON group. Moreover, supplementation with LPJZ-658 increased ileum and cecum length, duodenum and ileum villus height, and ileum villus height/crypt depth ratio. Furthermore, 16S rRNA sequencing revealed the dietary LPJZ-658 supplementation modulated the diversity and composition of cecal microflora. At the phylum level, the relative abundances of Proteobacteria, Actinobacteria, Verrucomicrobiota, and Acidobacteriota were significantly higher. In addition, LPJZ-658 substantially decreased the genus relative abundances of Streptococcus, Veillonella, Neisseria, and Haemophilus compared with the CON group and facilitated the growth and colonization of beneficial cecal bacteria, such as OBacteroides, Phascolarctobacterium, Bacillus, and Akkermansia. It was concluded that LPJZ-658 supplementation significantly increased growth production, improved meat quality and intestinal status, and modulated the intestinal microbiota in the broilers.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the gastrointestinal tract. This study aimed to determine the effect of cathelicidin-related antimicrobial peptide (Cramp) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice and to investigate the underlying mechanisms. Acute UC was induced in C57BL/6 mice with 3% DSS for 7 days, 4 mg/kg b.w. synthetic Cramp peptide was administrated once daily starting on day 4 of the experimental period. Mice were evaluated for body weight, colon length, colon histopathology, and inflammatory cytokines in colon tissue. Using 16 s rRNA sequencing, the composition structure of gut microbiota was characterized. Metabolomic profiling of the serum was performed. The results showed that DSS treatment significantly induced intestinal damage as reflected by disease activity index, histopathological features, and colon length, while Cramp treatment significantly prevented these trends. Meanwhile, Cramp treatment decreased the levels of inflammatory cytokines in both serum and colonic tissue on DSS-induced colitis. It was also observed that DSS damaged the integrity of the intestinal epithelial barrier, whereas Cramp also played a protective role by attenuating these deteriorated effects. Furthermore, Cramp treatment reversed the oxidative stress by increasing the antioxidant enzymes of GSH-PX and decreasing the oxidant content of MDA. Notably, compared to the DSS group, Cramp treatment significantly elevated the abundance of Verrucomicrobiota at the phylum level. Furthermore, at the genus level, Parasutterella and Mucispirllum abundance was increased significantly in response to Cramp treatment, although Roseburia and Enterorhabdus reduced remarkably. Metabolic pathway analysis of serum metabolomics showed that Cramp intervention can regulate various metabolic pathways such as α-linolenic acid, taurine and hypotaurine, sphingolipid, and arachidonic acid metabolism. The study concluded that Cramp significantly ameliorated DSS-induced colonic injury, colonic inflammation, and intestinal barrier dysfunction in mice. The underlying mechanism is closely related to the metabolic alterations derived from gut microbiota.

Fibroblast growth factor 21 (FGF21) is a glucose and lipid metabolic regulator. Recent research revealed that FGF21 was also induced by inflammatory stimuli. Its role in inflammatory bowel disease (IBD) has not been investigated. In this study, an experimental IBD model was established in FGF21 knockout (KO) and wild-type (WT) mice by adding 2.5% (wt/vol) dextran sodium sulfate (DSS) to their drinking water for 7 days. The severity of the colitis and the inflammation of the mouse colon tissues were analyzed. In WT mice, acute DSS treatment induced an elevation in plasma FGF21 and a significant loss of body weight in a time-dependent manner. Surprisingly, the loss of body weight and the severity of the colitis induced by DSS treatment in WT mice were significantly attenuated in FGF21 KO mice. Colon and circulating pro-inflammatory factors were significantly lower in the FGF21 KO mice compared to the WT mice. As shown by BrdU staining, the FGF21 KO mice demonstrated increased colonic epithelial cell proliferation. DSS treatment reduced intestinal Paneth cell and goblet cell numbers in the WT mice, and this effect was attenuated in the FGF21 KO mice. Mechanistically, FGF21 deficiency significantly increased the signal transducer and activator of transcription (STAT)-3 activation in intestinal epithelial cells and increased the expression of IL-22. Further study showed that the expression of suppressor of cytokine signaling-2/3 (SOCS 2/3), a known feedback inhibitor of STAT3, was significantly inhibited in the DSS-treated FGF2 KO mice compared to the WT mice. We conclude that FGF21 deficiency attenuated the severity of DSS-induced acute colitis, which is likely mediated by enhancing the activation of the IL-22-STAT3 signaling pathway in intestinal epithelial cells.

Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide; it is characterized by hepatic lipid accumulation, inflammation, and progressive fibrosis. Here, a Western diet combined with low-dose weekly carbon tetrachloride was fed to C57BL/6J mice for 12 weeks to build a NASH model to investigate the attenuating effects and possible mechanisms of Lactiplantibacillus plantarum LPJZ-658. Hepatic pathology, lipid profiles, and gene expression were assessed. The metabolomic profiling of the serum was performed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. The results show that LPJZ-658 treatment significantly attenuated liver injury, steatosis, fibrosis, and inflammation in NASH mice. Metabolic pathway analysis revealed that several pathways, such as purine metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and primary bile acid biosynthesis, were associated with NASH. Notably, we found that treatment with LPJZ-658 regulated the levels of bile acids (BAs) in the serum. Moreover, LPJZ-658 restored NASH-induced gut microbiota dysbiosis. The correlation analysis deduced obvious interactions between BAs and gut microbiota. The current study indicates that LPJZ-658 supplementation protects against NASH progression, which is accompanied by alternating BA metabolic and modulating gut microbiota.

Globally, metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), is one of the most common liver disorders and is strongly associated with copper deficiency. To explore the potential effects and mechanisms of Lactiplantibacillus plantarum LPJZ-658, copper deficiency combined with a high-sugar diet-induced MASLD mouse model was utilized in this study. We fed 40-week-old (middle-aged) male C57BL/6 mice a copper-deficient and high-sugar diet for 16 weeks (CuDS), with supplementary LPJZ-658 for the last 6 weeks (CuDS + LPJZ-658). In this study, we measured body weight, liver weight, and serum biochemical markers. Lipid accumulation, histology, lipidomics, and sphingolipid metabolism-related enzyme expression were investigated to analyze liver function. Untargeted metabolomics was used to analyze the serum and the composition and abundance of intestinal flora. In addition, the correlation between differential liver lipid profiles, serum metabolites, and gut flora at the genus level was measured. The results show that LPJZ-658 significantly improves abnormal liver function and hepatic steatosis. The lipidomics analyses and metabolic pathway analysis identified sphingolipid, retinol, and glycerophospholipid metabolism as the most relevant metabolic pathways that characterized liver lipid dysregulation in the CuDS group. Consistently, RT-qPCR analyses revealed that the enzymes catalyzing sphingolipid metabolism that were significantly upregulated in the CuDS group were downregulated by the LPJZ-658 treatment. In addition, the serum metabolomics results indicated that the linoleic acid, taurine and hypotaurine, and ascorbate and aldarate metabolism pathways were associated with CuDS-induced MASLD. Notably, we found that treatment with LPJZ-658 partially reversed the changes in the differential serum metabolites. Finally, LPJZ-658 effectively regulated intestinal flora abnormalities and was significantly correlated with differential hepatic lipid species and serum metabolites. In conclusion, we elucidated the function and potential mechanisms of LPJZ-658 in alleviating copper deficiency combined with sugar-induced middle-aged MASLD and hope this will provide possible treatment strategies for improving MASLD.