Abstract
The prophylactic use of lactic acid bacteria (LAB) to maintain human health is one of the most important research areas in recent times. LAB supplementation confers a wide range of health benefits to the host, but few studies have focused on their possible role in delaying the aging process. This study explored the health and life-promoting properties of two LAB, Levilactobacillus brevis and Weizmannia coagulans, using the Caenorhabditis elegans model. We found that L. brevis and W. coagulans enhanced the intestinal integrity and intestinal barrier functions without affecting the overall physiological functions of C. elegans. Wild-type worms preconditioned with LAB strains increased their survival under oxidative and thermal stress conditions by reducing intracellular reactive oxygen levels. Live L. brevis and W. coagulans significantly extended the lifespan of C. elegans under standard laboratory conditions independently of dietary restrictions. Genetic and reporter gene expression analysis revealed that L. brevis and W. coagulans extend lifespan via insulin/insulin-like growth factor-1 signaling and the p38 MAPK signaling axis. Furthermore, sirtuin, JNK MAPK, and mitochondrial respiratory complexes were found to be partially involved in W. coagulans-mediated lifespan extension and stress resilience. Preconditioning with LAB ameliorated age-related functional decline in C. elegans and reduced ectopic fat deposition in an NHR-49-dependent manner. Together, our findings indicated that L. brevis and W. coagulans are worth exploring further as “gerobiotic” candidates to delay aging and improve the healthspan of the host.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author(s) upon reasonable request.
References
Fontana L, Partridge L, Longo VD (2010) Extending healthy life span-From yeast to humans. Science 80(328):321–326. https://doi.org/10.1126/science.1172539
Roselli S, Guantario, et al (2019) Caenorhabditis elegans and probiotics interactions from a prolongevity perspective. Int J Mol Sci 20:5020. https://doi.org/10.3390/ijms20205020
Han B, Sivaramakrishnan P, Lin CCJ et al (2017) Microbial genetic composition tunes host longevity. Cell 169:1249-1262.e13. https://doi.org/10.1016/j.cell.2017.05.036
Claesson MJ, Jeffery IB, Conde S et al (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488:178–184. https://doi.org/10.1038/nature11319
Petrova P, Ivanov I, Tsigoriyna L et al (2021) Traditional Bulgarian dairy products: ethnic foods with health benefits. Microorganisms 9:480. https://doi.org/10.3390/microorganisms9030480
Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A (2019) Mechanisms of action of probiotics. Adv Nutr 10:S49–S66. https://doi.org/10.1093/advances/nmy063
Poupet C, Chassard C, Nivoliez A, Bornes S (2020) Caenorhabditis elegans, a host to Investigate the probiotic properties of beneficial microorganisms. Front Nutr 7. https://doi.org/10.3389/fnut.2020.00135
Murphy CT (2014) Insulin/insulin-like growth factor signaling in C elegans. WormBook. https://doi.org/10.1895/wormbook.1.164.1
Oh SW, Mukhopadhyay A, Svrzikapa N et al (2005) JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci 102:4494–4499. https://doi.org/10.1073/pnas.0500749102
Kondo M, Yanase S, Ishii T et al (2005) The p38 signal transduction pathway participates in the oxidative stress-mediated translocation of DAF-16 to Caenorhabditis elegans nuclei. Mech Ageing Dev 126:642–647. https://doi.org/10.1016/j.mad.2004.11.012
Kenyon CJ (2010) The genetics of ageing. Nature 464:504–512. https://doi.org/10.1038/nature09047
Komura T, Takemoto A, Kosaka H et al (2022) Prolonged lifespan, improved perception, and enhanced host defense of Caenorhabditis elegans by Lactococcus cremoris subsp. cremoris. Microbiol Spectr 10. https://doi.org/10.1128/spectrum.00454-21
Komura T, Ikeda T, Yasui C et al (2013) Mechanism underlying prolongevity induced by bifidobacteria in Caenorhabditis elegans. Biogerontology 14:73–87. https://doi.org/10.1007/s10522-012-9411-6
Patterson E, Ryan PM, Wiley N et al (2019) (2019) Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome. Sci Reports 91(9):1–15. https://doi.org/10.1038/s41598-019-51781-x
Cao J, Yu Z, Liu W et al (2020) Probiotic characteristics of Bacillus coagulans and associated implications for human health and diseases. J Funct Foods 64:103643. https://doi.org/10.1016/j.jff.2019.103643
Mohankumar A, Kalaiselvi D, Thiruppathi G et al (2022) Psychobiotics in health, longevity, and neurological disorders. Role of nutrients in neurological disorders. Springer, Singapore, pp 17–60
Zhao Y, Zhao L, Zheng X et al (2013) Lactobacillus salivarius strain FDB89 induced longevity in Caenorhabditis elegans by dietary restriction. J Microbiol 51:183–188. https://doi.org/10.1007/s12275-013-2076-2
Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77:71–94. https://doi.org/10.1002/cbic.200300625
Stiernagle T (2006) Maintenance of C. elegans. WormBook. https://doi.org/10.1895/wormbook.1.101.1
Oh A, Daliri EB-M, Oh DH (2018) Screening for potential probiotic bacteria from Korean fermented soybean paste: in vitro and Caenorhabditis elegans model testing. LWT 88:132–138. https://doi.org/10.1016/j.lwt.2017.10.007
Raveschot C, Coutte F, Frémont M et al (2020) Probiotic Lactobacillus strains from Mongolia improve calcium transport and uptake by intestinal cells in vitro. Food Res Int 133:109201. https://doi.org/10.1016/j.foodres.2020.109201
Son S-H, Yang S-J, Jeon H-L et al (2018) Antioxidant and immunostimulatory effect of potential probiotic Lactobacillus paraplantarum SC61 isolated from Korean traditional fermented food, jangajji. Microb Pathog 125:486–492. https://doi.org/10.1016/j.micpath.2018.10.018
Riaz Rajoka MS, Zhao H, Mehwish HM et al (2019) Anti-tumor potential of cell free culture supernatant of Lactobacillus rhamnosus strains isolated from human breast milk. Food Res Int 123:286–297. https://doi.org/10.1016/j.foodres.2019.05.002
Mohankumar A, Kalaiselvi D, Thiruppathi G et al (2020) α- and β-Santalols delay aging in Caenorhabditis elegans via preventing oxidative stress and protein aggregation. ACS Omega 5:32641–32654. https://doi.org/10.1021/acsomega.0c05006
Zhang Y, Lu H, Bargmann CI (2005) Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans. Nature 438:179–184. https://doi.org/10.1038/nature04216
Park MR, Yun HS, Son SJ et al (2014) Short communication: development of a direct in vivo screening model to identify potential probiotic bacteria using Caenorhabditis elegans. J Dairy Sci 97:6828–6834. https://doi.org/10.3168/jds.2014-8561
Mohankumar A, Shanmugam G, Kalaiselvi D et al (2018) East Indian sandalwood (Santalum album L.) oil confers neuroprotection and geroprotection in Caenorhabditis elegans via activating SKN-1/Nrf2 signaling pathway. RSC Adv 8:33753–33774. https://doi.org/10.1039/C8RA05195J
Gelino S, Chang JT, Kumsta C, et al. (2016) Intestinal autophagy improves healthspan and longevity in C. elegans during dietary restriction. PLoS Genet 12:e1006135. https://doi.org/10.1371/journal.pgen.1006135
Yen K, Le TT, Bansal A et al (2010) A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLoS ONE 5:1–10. https://doi.org/10.1371/journal.pone.0012810
Kos B, Šušković J, Vuković S et al (2003) Adhesion and aggregation ability of probiotic strain Lactobacillus acidophilus M92. J Appl Microbiol 94:981–987. https://doi.org/10.1046/j.1365-2672.2003.01915.x
Ram C, Chander H (2003) Optimization of culture conditions of probiotic bifidobacteria for maximal adhesion to hexadecane. World J Microbiol Biotechnol 19:407–410. https://doi.org/10.1023/A:1023946702949
Collado MC, Meriluoto J, Salminen S (2008) Adhesion and aggregation properties of probiotic and pathogen strains. Eur Food Res Technol 226:1065–1073. https://doi.org/10.1007/s00217-007-0632-x
Bargmann CI, Hartwieg E, Horvitz HR (1993) Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 74:515–527. https://doi.org/10.1016/0092-8674(93)80053-H
Alcedo J, Kenyon C (2004) Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron 41:45–55. https://doi.org/10.1016/S0896-6273(03)00816-X
Kumar A, Baruah A, Tomioka M et al (2020) Caenorhabditis elegans: a model to understand host–microbe interactions. Cell Mol Life Sci 77:1229–1249
Sim S, Hibberd ML (2016) Caenorhabditis elegans susceptibility to gut Enterococcus faecalis infection is associated with fat metabolism and epithelial junction integrity. BMC Microbiol 16:6. https://doi.org/10.1186/s12866-016-0624-8
Fan Y, Pedersen O (2021) Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 19:55–71
Sekirov I, Russell SL, Antunes CM, L, Finlay BB, (2010) Gut microbiota in health and disease. Physiol Rev 90:859–904
Dillin A, Hsu AL, Arantes-Oliveira N et al (2002) Rates of behavior and aging specified by mitochondrial function during development. Science 298:2398–2401. https://doi.org/10.1126/science.1077780
Ikeda T, Yasui C, Hoshino K et al (2007) Influence of lactic acid bacteria on longevity of Caenorhabditis elegans and host defense against Salmonella enterica serovar Enteritidis. Appl Environ Microbiol 73:6404–6409. https://doi.org/10.1128/AEM.00704-07
Park MR, Ryu S, Maburutse BE et al (2018) Probiotic Lactobacillus fermentum strain JDFM216 stimulates the longevity and immune response of Caenorhabditis elegans through a nuclear hormone receptor. Sci Rep 8:7441. https://doi.org/10.1038/s41598-018-25333-8
Lithgow GJ, White TM, Melov S, Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A 92:7540–7544. https://doi.org/10.1073/pnas.92.16.7540
Clancy D, Birdsall J (2013) Flies, worms and the Free Radical Theory of ageing. Ageing Res Rev 12:404–412
Mishra V, Shah C, Mokashe N et al (2015) Probiotics as potential antioxidants: a systematic review. J Agric Food Chem 63:3615–3626. https://doi.org/10.1021/jf506326t
Mohankumar A, Devagi G, Shanmugam G et al (2019) Organoruthenium(II) complexes attenuate stress in Caenorhabditis elegans through regulating antioxidant machinery. Eur J Med Chem 168:123–133. https://doi.org/10.1016/j.ejmech.2019.02.029
Uno M, Nishida E (2016) Lifespan-regulating genes in C. elegans. NPJ Aging Mech Dis 2:16010. https://doi.org/10.1038/npjamd.2016.10
Greer EL, Dowlatshahi D, Banko MR et al (2007) An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol 17:1646–1656. https://doi.org/10.1016/j.cub.2007.08.047
Lapierre LR, Hansen M (2012) Lessons from C. elegans: signaling pathways for longevity. Trends Endocrinol Metab 23:637–644
Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230. https://doi.org/10.1038/35065638
Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L (2006) C. elegans SIR-2.1 Interacts with 14–3-3 Proteins to activate DAF-16 and extend life span. Cell 125:1165–1177. https://doi.org/10.1016/j.cell.2006.04.036
Kenyon C (2011) The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing. Philos Trans R Soc B Biol Sci 366:9–16
Murphy CT (2013) Insulin/insulin-like growth factor signaling in C. elegans. WormBook 1–43. https://doi.org/10.1895/wormbook.1.164.1
Wu Z, Isik M, Moroz N et al (2019) Dietary restriction extends lifespan through metabolic regulation of innate immunity. Cell Metab 29:1192-1205.e8. https://doi.org/10.1016/j.cmet.2019.02.013
Inoue H (2005) The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev 19:2278–2283. https://doi.org/10.1101/gad.1324805
Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247
Anson RM, Hansford RG (2004) Mitochondrial influence on aging rate in Caenorhabditis elegans. Aging Cell 3:29–34
Bansal A, Zhu LJ, Yen K, Tissenbaum HA (2015) Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants. Proc Natl Acad Sci 112:E277–E286. https://doi.org/10.1073/pnas.1412192112
Pan C-L, Peng C-Y, Chen C-H, McIntire S (2011) Genetic analysis of age-dependent defects of the Caenorhabditis elegans touch receptor neurons. Proc Natl Acad Sci 108:9274–9279. https://doi.org/10.1073/pnas.1011711108
Palikaras K, Mari M, Petanidou B et al (2017) Ectopic fat deposition contributes to age-associated pathology in Caenorhabditis elegans. J Lipid Res 58:72–80. https://doi.org/10.1194/jlr.M069385
Stuhr NL, Curran SP (2020) Bacterial diets differentially alter lifespan and healthspan trajectories in C. elegans. Commun Biol 3:653. https://doi.org/10.1038/s42003-020-01379-1
Gilst MR Van, Hadjivassiliou H, Jolly A, Yamamoto KR (2005) Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans. PLoS Biol 3:e53. https://doi.org/10.1371/journal.pbio.0030053
Acknowledgements
Some strains used in this study were provided by the Caenorhabditis Genetics Center (CGC, University of Minnesota, MN), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). The Department of Science and Technology, Government of India is gratefully acknowledged for the financial support in the form of the DST-FIST program (No. SR/FST/LS-II/2017/111 (c); Dt: 25.01.2019) to the Department of Zoology, Bharathiar University, Tamil Nadu, India.
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Govindhan Thiruppathi and Amirthalingam Mohankumar conducted the experiments, analyzed the data, and wrote the original manuscript. Muthusamy Velumani and Duraisamy Kalaiselvi contributed to data analysis. Periyakali Saravana Bhavan and Paramasivam Premasudha helped with instrumentation and data interpretation. Shinkichi Tawata and Palanisamy Sundararaj conceptualized and supervised the project. All authors reviewed the manuscript and gave their final approval for publication.
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Thiruppathi, G., Mohankumar, A., Kalaiselvi, D. et al. Geroprotective Effect of Levilactobacillus brevis and Weizmannia coagulans in Caenorhabditis elegans. Probiotics & Antimicro. Prot. 16, 589–605 (2024). https://doi.org/10.1007/s12602-023-10060-y
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DOI: https://doi.org/10.1007/s12602-023-10060-y