Tomomi Komura

Abstract LPS-induced inflammation triggers metabolic reprogramming and nutritional decline. This study aimed to identify biomarkers for inflammatory and nutritional stress using GC-MS/MS-based metabolomic profiling. Male mice received LPS to induce systemic inflammation. Evaluations included liver histology (H&E, Gr-1), blood biochemistry, and metabolomic analysis of liver and plasma. LPS administration significantly increased hepatic neutrophil infiltration and liver enzymes, while decreasing nutritional markers (total protein, albumin, LDL-cholesterol). In the liver, LPS increased glycolytic and TCA cycle intermediates (e.g. 3-phosphoglycerate, citric acid) but decreased amino acids, including glutamine and tryptophan. Plasma analysis showed significant decreases in tryptophan, glucose, and succinic acid. Notably, tryptophan was significantly reduced in both compartments. Our findings demonstrate that tryptophan serves as a robust biomarker for monitoring the intersection of inflammatory response and nutritional status, reflecting synchronized metabolic shifts in the liver and plasma.

In Parkinson's disease (PD), α–synuclein (αSyn) accumulation drives neuropathological progression, establishing it as a potential therapeutic target. Lactic acid bacteria (LAB) provide various health benefits to the host and are expected to offer protective effects on neurological functions through the brain–gut connection, as indicated by animal studies. However, the protective effects of LAB against αSyn are not well understood. We investigated whether LAB feeding could reduce αSyn accumulation and improve mobility in transgenicCaenorhabditis elegans, an invertebrate model organism that expresses human αSyn in muscle. Among the nine screened strains,Pediococcus pentosaceussuppressed αSyn accumulation and the decrease in bending counts, a locomotion index in nematodes. Additionally, feedingP. pentosaceustoOryzias latipes(medaka), a vertebrate model organism, alleviated PD–like behavioral defects induced by 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine.P. pentosaseusacts as a probiotic against PD, and PD model worms and medaka can be used to screen effective LAB for prevention.

Several approaches for regulating health and disease by intestinal bacteria, bacteria isolated from food products, and food factors have been investigated; however, the molecular mechanisms underlying the interactions between these bacteria and their hosts are still unknown. Caenorhabditis elegans is a crucial model for exploring various biological phenomena and has been used in studying intestinal bacteria, mainly in the field of antiaging, anti-amyloid β activity in Alzheimer's disease, and its interaction to hosts. The nematode model is expected to be increasingly utilized for elucidating the interactions of beneficial bacteria or food factors with hosts. Herein, we review anti-aging and suppression of amyloid-β expression in a C. elegans model fed lactic acid bacteria, and our developed methods for orally administering food factors and assessing advanced glycation end products as an aging indicator.

Abstract Lactic acid bacteria (LAB) contribute to human health, and LAB functionality has been studied using Caenorhabditis elegans as an alternative host. However, many studies have focused on the efficacy of a single strain of LAB, and few reports have compared various LAB strains. In this study, we examined the effects of 15 strains of LAB isolated from vegetables, meat, and fermented foods on nematode longevity and healthy lifespan. To reduce the frequency of laborious survival observations, we performed a lifespan assay on agar plates containing 2′-deoxy-5-fluorouridine (FUdR), which inhibits egg-hatching and prevents generation mixing. Four beneficial strains showed significant lifespan extension and increased spontaneous nematode mobility, regardless of treatment with or without FUdR and the frequency of survival observation. These results suggested increased longevity and an extended healthy lifespan, which confirming the reliability of our method. The four strains are expected to show anti-ageing effects besides longevity and have effects on age-related degenerative diseases. Our labour-saving method can be used as an alternative to conventional methods and enable simultaneous screening of multiple strains. Future research could explore factors contributing to lifespan regulation by comparing and verifying differential strain effects on lifespan.

<named-content content-type="genus-species">Cutibacterium acnes</named-content> is one of the most common bacterial species residing on the human skin. Although the pathogenic properties of <named-content content-type="genus-species">C. acnes</named-content> , such as its association with acne vulgaris, have been widely described, its beneficial aspects have not been well characterized.

<title>Abstract</title>To assess the utility of autofluorescence as a noninvasive biomarker of senescence in <italic>Caenorhabditis elegans</italic>, we measured the autofluorescence of individual nematodes using spectrofluorometry. The fluorescence of each worm increased with age. Animals with lower fluorescence intensity exhibited longer life expectancy. When proteins extracted from worms were incubated with sugars, the fluorescence intensity and the concentration of advanced glycation end products (AGEs) increased over time. Ribose enhanced these changes not only in vitro but also in vivo. The glycation blocker rifampicin suppressed this rise in fluorescence. High-resolution mass spectrometry revealed that vitellogenins accumulated in old worms, and glycated vitellogenins emitted six-fold higher fluorescence than naive vitellogenins. The increase in fluorescence with ageing originates from glycated substances, and therefore could serve as a useful noninvasive biomarker of AGEs. <italic>C. elegans</italic> can serve as a new model to look for anti-AGE factors and to study the relationship between AGEs and senescence.

<title>ABSTRACT</title>This study evaluated whether the lactic acid bacteria <italic>Lactococcus lactis</italic> subsp. <italic>cremoris</italic> strain FC (FC) could ameliorate host defenses and cognitive ability and extend the lifespan of <italic>Caenorhabditis elegans</italic>, a model of senescence. The lifespan and resistance to physical, chemical, and biological stressors were compared between <italic>C. elegans</italic> fed FC and those fed <italic>Escherichia coli</italic> OP50 (OP), an international standard food for <italic>C. elegans</italic>. Living FC successfully extended the health span, enhanced host defense, and ameliorated the cognitive ability of the nematodes; even the exopolysaccharides (EPSes) of FC could extend the lifespan of <italic>C. elegans</italic>. The chemotaxis index, which was used to evaluate the senescence of sensory neurons, tended to decrease with aging; however, it was more stable in worms fed FC and was significantly higher than that of the control worms at 7 days of age. The worms fed FC were tolerant to <italic>Salmonella enterica</italic> serovar Enteritidis or <italic>Staphylococcus aureus</italic> infection and had better survival than the control worms fed OP. FC showed beneficial effects in <italic>C. elegans daf-16</italic> and <italic>pmk-1</italic> mutants, but not in <italic>skn-1</italic> mutants. Since SKN-1 is the <italic>C. elegans</italic> ortholog of Nrf2, we measured the transcription of heme oxygenase-1 (HO-1), which is regulated by Nrf2, in murine macrophages and found that HO-1 mRNA expression was increased &gt;5 times by inoculation with either FC cells or heat-killed bacteria with EPSes. Thus, both FC and the EPSes can affect longevity <italic>via</italic> the SKN-1/Nrf2 pathway in both nematodes and mammalian cells. <sec><title>IMPORTANCE</title>Ageing is one of our greatest challenges. The World Health Organization proposed the concept of “Active Ageing” might encourage people to continue to work according to their capacities and preferences as they grow old and would prevent or delay disabilities and chronic diseases that are costly to both individuals and the society, considering that disease prevention is more economical than treatment. Probiotic bacteria such as lactobacilli are living microorganisms that exert beneficial effects on human health when ingested in sufficient amounts and can promote longevity. The significance of this study is that it revealed the anti-senescence and various beneficial effects of the probiotic representative bacterium <italic>Lactococcus lactis</italic> subsp. <italic>cremoris</italic> strain FC and its exopolysaccharides in the nematode <italic>Caenorhabditis elegans</italic>. </sec>

Bifidobacterium infantis, a Gram-positive bacterium, is one of the commonly used probiotics. We previously showed that B. infantis modified host defense systems and extended the lifespan of the nematode Caenorhabditis elegans. In the present study, we showed that the lifespan extension caused by B. infantis was enhanced in animals having a mutation in the tol-1 gene that encodes the sole C. elegans homolog of Toll-like receptors (TLRs). Meanwhile, lifespan increased by other probiotic bacteria, such as Bacillus subtilis or Clostridium butyricum, was not affected in the tol-1 mutant animals. A microarray analysis revealed that the expression of innate immune response-related genes was significantly increased in the tol-1 mutant. Worms with the tol-1 mutation exhibited reduced leaving behavior from the B. infantis lawn, while canonical downstream factors trf-1/TRAF and ikb-1/IκB appeared to not be involved. In conclusion, C. elegans tol-1/TLR regulates B. infantis-induced longevity and also regulates behavior against B. infantis.