Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress and Increases Lifespan in Caenorhabditis elegans

Abstract

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 (3 mM and 5 mM 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%. Moreover, transcriptomic analysis of C. elegans fed with this strain showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. This strain also had a clear anti-inflammatory profile when co-cultured with HT-29 cells, stimulated by pro-inflammatory cytokines, and co-culture systems with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation in a murine model of colitis. This work suggests that C. elegans is a fast, predictive and convenient screening tool to identify new potential antioxidant probiotic strains for subsequent use in humans.

Genetically Engineered Immunomodulatory Streptococcus thermophilus Strains Producing Antioxidant Enzymes Exhibit Enhanced Anti-Inflammatory Activities

“…We hypothesize that the increased survival of these animals might be related to a more efficient reduction of ROS in the presence of both enzymes (CAT and SOD), conferring a higher antioxidant protection. Moreover, in a recent study it has been shown that an anti-inflammatory strain of L. rhamnosus CNCMI-3690 protected against oxidative stress and increased the life span in Caenorhabditis elegans through a differential expression of the DAF-16/insulin-like pathway (28). It is also important to note that in both protocols of administration, WT S. thermophilus CRL 807 also decreased the severity of the inflammation compared to that in the TNBS control group, corroborating the innate antiinflammatory potential of this strain selected by in vitro and in vivo assays.…”

Evaluation of Role of Oxidative Stress on Aging in Caenorhabditis elegans: A Brief Review

“…Supplementation of C. elegans incubation media with a strain of lactic acid bacteria Lactobacillus rhamnosus CNCMI-3690, which exhibits antioxidant activity, increased lifespan and protected against oxidative stress. This strain of lactic acid producing bacteria also reduced inflammation [15]. These studies suggest that increased levels of antioxidants extend the lifespan by reducing oxidative stress and possibly by other mechanisms, such as preventing deregulation of protective transcriptional factors.…”

Forkhead Box Protein O1 is Linked to Anti-Inflammatory Probiotic Bacteria Acting through Nuclear Factor-κB Pathway

“…The transcription factor FoxO1 has been related to the response of probiotics in C. elegans oxidative stress, skin acne and alcoholic fatty liver [22,45,46]. Nevertheless, this is the first study linking FoxO1 activation to probiotics response in intestinal mammalian cells.…”

“…Previous finding from our group demonstrated that FoxO1 homologous gene in C. elegans, daf-16, is involved in the protection exerted by probiotics from oxidative stress induced by H 2 O 2 in this organism [22]. Based on these findings, we wanted to explore if this transcription factor was also related to the oxidative stress response in mammalian cells.…”

“…Conversely, phosphorylation of FoxO1 by Akt causes its release from DNA, binding to 14-3-3 protein and rapidly relocating from the nucleus to the cytoplasm, where it becomes inactive [21]. It has been described that C. elegans FoxO1 homologous, daf-16, has been involved in the anti-inflammatory and antioxidant effect of the Lactobacillus rhamnosus CNCM I-3690 strain [22].…”