A Potential Probiotic Lactobacillus plantarum JBC5 Improves Longevity and Healthy Aging by Modulating Antioxidative, Innate Immunity and Serotonin-Signaling Pathways in Caenorhabditis elegans

Abstract

Since the hypothesis of Dr. Elie Metchnikoff on lactobacilli-mediated healthy aging, several microbes have been reported to extend the lifespan with different features of healthy aging. However, a microbe affecting diverse features of healthy aging is of choice for broader acceptance and marketability as a next-generation probiotic. We employed Caenorhabditis elegans as a model to understand the potential of Lactobacillus plantarum JBC5 (LPJBC5), isolated from fermented food sample on longevity and healthy aging as well as their underlying mechanisms. Firstly, LPJBC5 enhanced the mean lifespan of C. elegans by 27.81% compared with control (untreated). LPBC5-induced longevity was accompanied with better aging-associated biomarkers, such as physical functions, fat, and lipofuscin accumulation. Lifespan assay on mutant worms and gene expression studies indicated that LPJBC5-mediated longevity was due to upregulation of the skinhead-1 (skn-1) gene activated through p38 MAPK signaling cascade. Secondly, the activated transcription factor SKN-1 upregulated the expression of antioxidative, thermo-tolerant, and anti-pathogenic genes. In support, LPJBC5 conferred resistance against abiotic and biotic stresses such as oxidative, heat, and pathogen. LPJBC5 upregulated the expression of intestinal tight junction protein ZOO-1 and improved gut integrity. Thirdly, LPJBC5 improved the learning and memory of worms trained on LPJBC5 compared with naive worms. The results showed upregulation of genes involved in serotonin signaling (ser-1, mod-1, and tph-1) in LPJBC5-fed worms compared with control, suggesting that serotonin-signaling was essential for LPJBC5-mediated improved cognitive function. Fourthly, LPJBC5 decreased the fat accumulation in worms by reducing the expression of genes encoding key substrates and enzymes of fat metabolism (i.e., fat-5 and fat-7). Lastly, LPJBC5 reduced the production of reactive oxygen species and improved mitochondrial function, thereby reducing apoptosis in worms. The capability of a single bacterium on pro-longevity and the features of healthy aging, including enhancement of gut integrity and cognitive functions, makes it an ideal candidate for promotion as a next-generation probiotic.

Novel Probiotic Lactic Acid Bacteria Were Identified from Healthy Infant Feces and Exhibited Anti-Inflammatory Capacities

“…Several antioxidant enzymes including SOD, GPx, GSH, GSSG and HO-1 are secreted to protect cells against oxidative damage. In accordance with other studies, these enzymes were collectively enhanced and ROS production was reduced by our selected LAB [ 53 , 54 , 55 ]. Nrf2 has long been considered a cytoprotective factor regulating anti-inflammatory and anti-oxidative proteins.…”

Synbiotics and Their Antioxidant Properties, Mechanisms, and Benefits on Human and Animal Health: A Narrative Review

“…L. plantarum GKM3 delayed the process of aging, alleviated age-related cognitive impairment, and reduced oxidative stress in mice models [ 121 ]. Recent findings suggest that L. plantarum JBC5 activated the p38 MAPK pathway and its downstream targets in worms ( Caenorhabditis elegans ) to enhance longevity by improving stress resistance, immunity, and other age-associated pathologies [ 122 ]. Other probiotics, such as B. amyloliquefaciens B-1895 and B. subtilis KATMIRA1933 also induce DNA protective and antioxidant activity [ 123 ].…”

Emerging cellular senescence-centric understanding of immunological aging and its potential modulation through dietary bioactive components

“…For example, a recent study reported that consumption of probiotic Lactobacillus casei CRL 431 in aged mice not only improved the cellular and functional markers of immunosenescence but also restored the age-related loss in the thymus medulla (Balcells et al 2022 ). Probiotic Lactobacillus plantarum JBC5 enhanced the lifespan of Caenorhabditis elegans through the modulation of multiple markers related to oxidative stress and innate immunity (Kumar et al 2022 ). Application of a probiotic cocktail containing 5 Lactobacillus and 5 Enterococcus strains to old mice prevented the leaky gut by improving the expression of tight junction proteins that ultimately prevented unwarranted aggravation of intestinal immune cells and thus inflammation (Ahmadi et al 2020 ).…”