Project description:Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total) and nematode viability was assessed after oxidative stress (3mM and 5mM H2O2). One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. We performed a transcriptomic analysis of C. elegans fed with this strain and showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. Gene expression in C. elegans wild-type strain (N2) was analyzed in worm populations fed with E. coli OP50 (control condition) or the corresponding LAB (Lactobacillus rhamnosus CNCM I-3690 or Lactobacillus rhamnosus CNCM I-4317) . Three days and ten days feeding period was analyzed.
Project description:we have performed transcriptomic analysis of colonic samples of mice challenged with DNBS twice in a chronic model of inflammation and treated with CNCM -I3690 strain and several mutants and variants generated from it. colonic transcriptome analysis at the endpoint revealed that CNCM I 3690 enhances the expression of genes related to healthy gut permeability, motility (Ghrelin (GHR)), and absorption (guanylate cyclase activator 2B (Guca 2b)); cell proliferation (amino acid transporter SLC7A7); and protective functions (endogenous protease inhibitor kazal-type4). Focusing on inflammation, both GHR and Guca 2B have been found to act as anti-inflammatory, protecting the gut against a wide range of threats. Besides, CNCM I-3690 also up regulated TRAF-interaction protein with a forkhead-associated domain (TIFA), an important signaling adaptor in the NF-κβ pathway.
Project description:Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis remains unknown. Here, we showed that B. wadsworthia synergize with HFD to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis unraveled pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B. wadsworthia. Pharmacological suppression of B. wadsworthia-associated inflammation unmasked the bacterium’s intrinsic capacity to induce a negative impact on glycemic control and hepatic function. Finally, the probiotic Lactobacillus rhamnosus CNCM I-3690 was able to limit B. wadsworthia-induced immune and metabolic impairment by limiting its expansion, reducing inflammation and reinforcing intestinal barrier. Our results support a new avenue for interventions against western diet-driven inflammatory and metabolic diseases.
Project description:Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis remains unknown. Here, we showed that B. wadsworthia synergize with HFD to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis unraveled pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B. wadsworthia. Pharmacological suppression of B. wadsworthia-associated inflammation unmasked the bacterium’s intrinsic capacity to induce a negative impact on glycemic control and hepatic function. Finally, the probiotic Lactobacillus rhamnosus CNCM I-3690 was able to limit B. wadsworthia-induced immune and metabolic impairment by limiting its expansion, reducing inflammation and reinforcing intestinal barrier. Our results support a new avenue for interventions against western diet-driven inflammatory and metabolic diseases.
Project description:Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total) and nematode viability was assessed after oxidative stress (3mM and 5mM H2O2). One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. We performed a transcriptomic analysis of C. elegans fed with this strain and showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans.
Project description:Lacticaseibacillus rhamnosus GG (LGG) is a widely consumed probiotic whose potential beneficial effects in humans have been examined in over 250 clinical trials. However, the mechanisms by which LGG modulates host gut physiology remains unknown. R. gnavus is a pathobiont that is strongly associated with inflammatory bowel diseases. Germ free mice were mono-associated with L. rhamonosus (LGG) or R. gnavus (RG) for 21 days, ileum bulk RNA-seq were performed to compare the transcriptomic profiles of LGG or RG associated mice with the transcriptome of germ-free mouse ileum.
Project description:The human microbiota is believed to influence health. Microbiome dysbiosis may be linked to neurological conditions like Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). We report the ability of a probiotic bacterial strain in halting neurodegeneration phenotypes. We show that Lacticaseibacillus rhamnosus HA-114 is neuroprotective in C. elegans models of ALS and HD. Our results show that neuroprotection from L. rhamnosus HA-114 is unique from other L. rhamnosus strains, and resides in its fatty acid content. Neuroprotection by L. rhamnosus HA-114 requires acdh-1/ACADSB, kat-1/ACAT1 and elo-6/ELOVL3/6, which are key fatty acid metabolism and mitochondrial b-oxidation genes. Our data suggest that disrupted lipid metabolism contributes to neurodegeneration and that dietary intervention with L. rhamnosus HA-114 restores lipid homeostasis and energy balance through mitochondrial b-oxidation. L. rhamnosus HA-114 is suitable for human consumption opening the possibility of modifying disease progression by dietary intervention.
Project description:Identification of proteins contained in extracellular vesicles of Lacticaseibacillus rhamnosus PCM 489. Dataset is related to publication http://dx.doi.org/10.20517/evcna.2024.49. This work was financially supported by the National Science Centre, Poland (no. 2021/43/D/NZ6/01464).