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An overlooked prebiotic: beneficial effect of dietary nucleotide supplementation on gut microbiota and metabolites in senescence-accelerated mouse prone-8 mice

ABSTRACT: Nucleotides (NTs) are regulatory factors in many biological processes and play important roles in the growth, development, and metabolism of living organisms. We used senescence-accelerated mouse prone-8 (SAMP8) to investigate the effects of NTs on the gut microbiota and metabolites. And the promoting effect of NTs on the growth of a probiotic (Lactobacillus casei) was explored through in vitro experiments. The results showed that the sequencing depth of 16S rDNA covered all microbial species in the feces of SAMP8. Supplementation with exogenous NTs to the diet enhanced the diversity of the gut microbiota, reduced the abundance of bacteria with negative effects on the body (such as Verrucomicrobia, Ruminococcaceae, Akkermansia and Helicobacter), and increased the abundance of the microbiota, which had beneficial effects on the mice (such as Lactobacillus, Candidatus saccharimonas and Lachnospiraceae_NK4A136_group). Metabonomic analysis showed that NT deficiency in the diet significantly affected metabolites in the mouse feces. The metabolites in mice supplemented with NTs tended to be normal (SAMR1). The differentially expressed metabolites caused by NT addition are involved in various pathways in the body, including linoleic acid metabolism, vitamin B6 metabolism, and histidine metabolism. Correlation analysis revealed a significant correlation between the gut microbiota and differentially expressed metabolites caused by the addition of NTs. In vitro experiments showed that NTs significantly promoted the growth, secretion of biofilm and extracellular polymeric substance of L. casei. NTs also promoted the ability of the crude extract of L. casei to resist the secretion of Shigella biofilm. Thus, NTs can regulate the abundance of the gut microbiota and alter the metabolic expression of the intestinal microbiome.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

SUBMITTER: Lixia Song

PROVIDER: MTBLS4012 | MetaboLights | 2022-03-21

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS4012	Other
	FILES	Other
	a_MTBLS4012_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS4012_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	files-all.json	Other

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Project description:Familial Mediterranean fever (FMF) is an inflammatory genetic disease characterized by elevated systemic reactivity against commensal gut microbiota and high levels of gut Candida albicans. The current study investigated the effects of Lactobacillus acidophillus INMIA 9602 Er 317/402 strain (probiotic “Narine”) on the relative abundance of gut enteric bacteria, lactobacilli, Staphylococcus aureus, and Enteroccocus faecalis in Candida albicans-carrier and non-carrier FMF patients in remission with the main MEFV mutation patterns M694V/V726A- the prevalent MEFV gene mutation within FMF patients in the Armenian cohort. Our data revealed that M694V/V726A mutations in PURIN inflammasome leading to FMF disease brought to gender specific differences in microbial community structure in FMF patients. Possibly, long-term colchicine use suppresses the PURIN inflammasome/inhibits NLRP3 inflammasome-dependent IL-1β release influencing on overgrowth of C. albicans in gut microbiota of FMF patients. The comparison of Operational Taxonomic Units (OTUs) of enteric bacteria in C. albicans-carrier and non-carrier female patients revealed the statistically significant increase in OTUs of enterobacteria in C. albicans-carriers. In contrast to this, there were no differences in abundance of Enteroccocus faecalis between female FMF C. albicans-carriers compared with non-carriers, while male FMF C. albicans-carriers have increased abundance of E. faecalis in their gut microbiota compared with that of male patients with none carriers. The gut microbiota of FMF patients (both male and female) with C. albicans below baseline level contains high abundance of lactobacilli compared with C. albicans-carriers. The adoption of Lactobacillus acidophilus INMIA 9602 Er 317/402 leads to changes in gut microbiota composition of FMF patients. It reduces, in particularly, the abundance of enterobacteria in females, and Enteroccocus faecalis in men parallel with reducing the numbers of yeast in gut microbiota of FMF patients. We hypothesize that colchicine treatment changes the already-altered gut microbiota of FMF patients, thereby affecting the regulation of immune system by inhibition of NLRP3 inflammasome. Colchicine could lead to overgrowth of C. albicans in gut microbiota of FMF patients, whereas the Lactobacillus acidophilus INMIA 9602 Er 317/402 works on activation of inflammasome by new changes in gut microbiota of patients.

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An overlooked prebiotic: beneficial effect of dietary nucleotide supplementation on gut microbiota and metabolites in senescence-accelerated mouse prone-8 mice

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