Stachyose inhibits vancomycin-resistant Enterococcus colonization and affects gut microbiota in mice.

Vancomycin-resistant Enterococcus (VRE) caused nosocomial infections are rising globally. Multiple measures have been investigated to address this issue, altering gut microbiota through dietary intervention represents one of such effort. Stachyose can promote probiotic growth, which makes it a good candidate for potentially inhibiting VRE infection. This study aimed to determine whether stachyose inhibits VRE colonization and investigated the involvement of gut microbiota this effect of stachyose. In VRE-infection experiment, 6-week old female C57/6 J mice pre-treated with vancomycin were infected with 2 × 108 CFU VRE via gavage. These mice then received oral administration of stachyose or PBS as control for 7days. Two groups of uninfected mice were also received daily gavage of stachyose or PBS for 7 days to observe the impact of stachyose treatment on normal mice. Fresh fecal and colon samples were collected, then VRE colonization, gut microbiota and gene expression were respectively assessed using cultivation, 16s rRNA sequencing and RNA-sequencing in two parallel experiment, respectively. In VRE-infected mice, stachyose treatment significantly reduced VRE colonization on days 9 and 10 post-infection. Stachyose treatment increased the relative abundance of Porphyromonadaceae, Parabacteroides, and Parabacteroides distasonis compared to the PBS-treated infection mice (P < 0.01). Uninfected mice treated with stachyose showed a significant increase in Lactobacillaceae and Lactobacillus compared to the PBS-treated uninfected mice(P < 0.05). RNA-sequencing results showed that stachyose treatment in VRE-infected mice increased expression of genes involved in TNF and IL-17 signaling pathways. Stachyose treatment also up-regulated Hsd17b14, Cyp3a44, Arg1, and down-regulated Pnliprp2, Ces1c, Pla2g4c genes involving in metabolic pathway in uninfected mice. In conclusion, stachyose supplementation can effectively inhibit VRE colonization and probably altering composition of the microbiome, which can in turn result in changes in expression of genes. Stachyose may also benefit health by increasing the abundance of Lactobacillus and expression of genes involving in metabolic pathway in normal mice.

[Effects of Lactobacillus paragasseri Y20 on cholesterol-lowering, intestinal microbiota and liver metabolism in rats with hypercholesterolaemia].

OBJECTIVE: To evaluate the cholesterol-lowering effects of Lactobacillus paragasseri Y20 on rats with high cholesterol diet and its effect on the gut microbiota of rats, and to explore the potential mechanism of Lactobacillus paragasseri regulating hypercholesterolemia in rats. METHODS: Thirty rats were randomly divided into three groups and were treated with normal diet, high cholesterol diet+PBS, and high cholesterol diet+Lactobacillus paragasseri Y20, respectively. After five consecutive weeks of treatment, serum lipids were measured by ELISA. Rat feces were collected and DNA was extracted for 16 S rRNA amplicon sequencing analysis. Rat livers were collected and analyzed for non-targeted metabolites using high performance liquid chromatography. RESULTS: Compared with the high-cholesterol model group, Lactobacillus paragasseri Y20 treatment could reduce the serum triglyceride and low-density lipoprotein concentrations and increase the high-density lipoprotein concentration in rats. High-cholesterol diet decreased the intestinal flora diversity and richness of rats, while Y20 intervention can effectively restore the change of intestinal flora of high-cholesterol rats. High cholesterol dietsmainly caused the changes in the relative abundance in phylum of Firmicutes, Deferribacteres, Verrucomicrobia, and Proteobacteria, increasing Akkermansia, Clostridium_III, and Clostridium_XIVbgenera, and decreasing the intestinimonasgenus. However, Y20 intervention restored the diversity of gut microbiota and alteration in relative abundance of these bacteria caused by high-cholesterol diet. Y20 could effectively decrease the higher relative abundance of Akkermansiahigh-cholesterol diet. CONCLUSION: Lactobacillus paragasseri Y20 can alleviate hypercholesterolemia in rats, regulate the gut microbiotadiversity and composition and affect liver metabolism in hypercholesterol rats.

Effect of Lactobacillus plantarum HT121 on serum lipid profile, gut microbiota, and liver transcriptome and metabolomics in a high-cholesterol diet-induced hypercholesterolemia rat model.

OBJECTIVES: The aim of this study was to evaluate effect of Lactobacillus plantarum HT121 on serum lipid profile, gut microbiota, and liver transcriptome and metabolomics. METHODS: L. plantarum HT121 was selected by screening of acid and bile salt tolerance and cholesterol assimilation assay. Sprague Dawley rats were randomly divided into three groups and fed the respective diets for 7 wk: normal chow diet (NCD), high-cholesterol diet (HCD), and high-cholesterol diet plus L. plantarum HT121 (HT121). After 7 wk, blood lipid profile was measured by enzyme-linked immunosorbent assay, gut microbiota was determined by 16 S rRNA sequencing, gene expression, and bile acids in liver were detected by transcriptome and metabolomics, respectively. RESULTS: L. plantarum HT121 feeding decreased serum triacylglycerols (TGs), total cholesterol (TC), and low-density lipoprotein (LDL), and increased serum high-density lipoprotein levels. HT121 treatment increased the α-diversity in the HT121 group to a level close to that in the NCD group, and restored the genera of Adlercreutzia, Mucispirillum, Ruminococcus, Clostridium, Blautia, Roseburia, and Akkermansia to levels similar to those in the NCD group. Furthermore, the high-cholesterol diet decreased taurocholic acid (TCA) and increased taurochenodeoxycholic acid (TCDCA) and glycocholic acid (GCA) in the liver; all these changes were reversed by HT121 treatment, bringing the levels close to those in the NCD group. Finally, HT121 treatment increased expression of bile secretion-related genes Cyp7 a1 in rat liver, which was positively correlated with TG, Clostridium, and GCA. Spearman's correlation analysis showed that TGs, TC, and LDL were positively correlated with the relative abundance of genera of Blautia, Clostridium, and Roseburia, and levels of bile acid glycocholic acid, and inversely correlated with the relative abundance of Ruminococcus and Mucispirillum. CONCLUSIONS: L. plantarum HT121 can improve serum lipid profiles in a high-fat diet-induced rat model, which may be attributed to alteration in gut microbiota and bile acid metabolism.

Two Strains of Lactobacilli Effectively Decrease the Colonization of VRE in a Mouse Model.

Vancomycin-resistant Enterococcus (VRE) infection is a serious challenge for clinical management and there is no effective treatment at present. Fecal microbiota transplantation (FMT) and probiotic intervention have been shown to be promising approaches for reducing the colonization of certain pathogenic bacteria in the gastrointestinal tract, however, no such studies have been done on VRE. In this study, we evaluated the effect of FMT and two Lactobacillus strains (Y74 and HT121) on the colonization of VRE in a VRE-infection mouse model. We found that both Lactobacilli strains reduced VRE colonization rapidly. Fecal microbiota and colon mRNA expression analyses further showed that mice in FMT and the two Lactobacilli treatment groups restored their intestinal microbiota diversity faster than those in the phosphate buffer saline (PBS) treated group. Administration of Lactobacilli restored Firmicutes more quickly to the normal level, compared to FMT or PBS treatment, but restored Bacteroides to their normal level less quickly than FMT did. Furthermore, these treatments also had an impact on the relative abundance of intestinal microbiota composition from phylum to species level. RNA-seq showed that FMT treatment induced the expression of more genes in the colon, compared to the Lactobacilli treatment. Defense-related genes such as defensin α, Apoa1, and RegIII were down-regulated in both FMT and the two Lactobacilli treatment groups. Taken together, our findings indicate that both FMT and Lactobacilli treatments were effective in decreasing the colonization of VRE in the gut.

Consortium of Probiotics Attenuates Colonization of Clostridioides difficile.

Clostridioides difficile infection (CDI) is increasing morbidity and mortality rates globally. Fecal microbiota transplantation (FMT), an effective therapy for eliminating Clostridioides difficile (C. difficile), cannot be used extensive due to a range of challenges. Probiotics thus constitutes a promising alternative therapy. In our study, we evaluated the effect of consortium of probiotics including five Lactobacilli strains and two Bifidobacterium strains on the colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. The results of 16S rRNA sequencing and targeted metabolomics showed the consortium of probiotics effectively decreased the colonization of C. difficile, changed the α- and ß-diversity of the gut microbiota, decreased the primary bile acids, and increased the secondary bile acids. Spearman's correlation showed that some of the OTUs such as Akkermansia, Bacteroides, Blautia et al. were positively correlated with C. difficile numbers and the primary bile acids, and negatively correlated with the secondary bile acids. However, some of the OTUs, such as Butyricicoccus, Ruminococcus, and Rikenellaceae, were negatively correlated with C. difficile copies and the primary bile acids, and positively correlated with the secondary bile acids. In summary, the consortium of probiotics effectively decreases the colonization of C. difficile, probably via alteration of gut microbiota and bile acids. Our probiotics mixture thus offers a promising FMT alternative.