{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:05:24Z","timestamp":1789988724714,"version":"4.0.1"},"reference-count":98,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Aging is characterized by gradual shifts in cellular and physiological processes, even in individuals who remain apparently clinically healthy. These changes reflect a coordinated decline in metabolic efficiency, immune regulation, organ function, psychological resilience, and sleep integrity, domains increasingly recognized as interconnected determinants of apparently healthy aging. This study explored age- and sex-associated patterns in multidimensional physiological domains and gut microbiota features among 45 apparently healthy middle-aged and elderly participants across four age\u2013sex groups (middle-aged males, n = 13; middle-aged females, n = 11; elderly males, n = 13; elderly females, n = 8). Comprehensive clinical, metabolic, inflammatory, hepato-renal, psychological, and sleep parameters were standardized into domain-specific Z-scores, which were integrated into a composite multidimensional physiological health index (MPHI), a systems-level physiological index developed as a proxy for physiological processes associated with mitochondrial function and apparently healthy aging rather than a direct measure of mitochondrial biology. Whole-metagenome sequencing and MetaPhlAn-based taxonomic profiling were used to characterize gut microbiota composition and diversity. Despite no statistically significant overall differences among the four age\u2013sex groups in multivariate analysis (MANOVA, p = 0.103) and gut microbial community structure (PERMANOVA, p = 0.651), descriptive variation was observed across several physiological domains, while microbiota\u2013host associations remained exploratory and nominal after FDR correction. Middle-aged males showed comparatively less favorable metabolic and inflammatory profiles, while selected psychosocial and sleep-related measures showed variation across the age\u2013sex groups, particularly among elderly females. Principal component analysis (PCA) of domain scores indicated multidimensional physiological variation influenced by inflammatory, metabolic, and hepato-renal indices, although substantial overlap was observed among the age\u2013sex groups. The MPHI showed descriptive variation across the groups, with elderly males showing the highest composite scores and middle-aged females the lowest. Overall, the apparently healthy cohort showed subtle variation across interconnected physiological domains in the absence of overt differences in gut microbial community structure. These findings support the potential utility of composite physiological indices for exploratory characterization of multidimensional physiological variation during aging, while highlighting the need for validation in larger independent cohorts and against direct mitochondrial biomarkers.<\/jats:p>","DOI":"10.3390\/microorganisms14092097","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:25:43Z","timestamp":1789986343000},"page":"2097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidimensional Physiological and Gut Microbiome Profiling Identifies Subtle Physiological Patterns in an Apparently Healthy Aging Indian Cohort: A Cross-Sectional Observational Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-8766","authenticated-orcid":false,"given":"Gangaraju","family":"Divyashri","sequence":"first","affiliation":[{"name":"Bioproducts Research, Iom Bioworks Pvt. Ltd.,  Centre for Cellular and Molecular Platforms (C-CAMP), GKVK Campus,  Bengaluru 560 065, India"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7839-0840","authenticated-orcid":false,"given":"Harini","family":"Hutti","sequence":"additional","affiliation":[{"name":"Bioproducts Research, Iom Bioworks Pvt. Ltd.,  Centre for Cellular and Molecular Platforms (C-CAMP), GKVK Campus,  Bengaluru 560 065, India"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4279-4181","authenticated-orcid":false,"given":"Lalitha Prasanna","family":"Madduri Venkata","sequence":"additional","affiliation":[{"name":"Bioproducts Research, Iom Bioworks Pvt. Ltd.,  Centre for Cellular and Molecular Platforms (C-CAMP), GKVK Campus,  Bengaluru 560 065, India"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Bipin Pradeep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Bioproducts Research, Iom Bioworks Pvt. Ltd.,  Centre for Cellular and Molecular Platforms (C-CAMP), GKVK Campus,  Bengaluru 560 065, India"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Ayako","family":"Yachie","sequence":"additional","affiliation":[{"name":"SBX Biosciences Inc., 885 West Georgia Street, 20th Floor, Vancouver, BC V6C 3E8, Canada"},{"name":"The Systems Biology Institute, Tokyo 141-0022, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samik","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Bioproducts Research, Iom Bioworks Pvt. Ltd.,  Centre for Cellular and Molecular Platforms (C-CAMP), GKVK Campus,  Bengaluru 560 065, India"},{"name":"The Systems Biology Institute, Tokyo 141-0022, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101955","DOI":"10.1016\/j.arr.2023.101955","article-title":"Mitochondrial dysfunction in aging","volume":"88","author":"Guo","year":"2023","journal-title":"Aging Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2147\/CIA.S158513","article-title":"Oxidative stress, aging, and diseases","volume":"13","author":"Liguori","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and aging-related diseases: From molecular mechanisms to interventions and treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1152\/physrev.00045.2024","article-title":"Biomarkers of aging: From molecules and surrogates to physiology and function","volume":"105","author":"Furrer","year":"2025","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"San-Mill\u00e1n, I. (2023). The key role of mitochondrial function in health and disease. Antioxidants, 12.","DOI":"10.3390\/antiox12040782"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/BF02432509","article-title":"Free radical theory of aging: Consequences of mitochondrial aging","volume":"6","author":"Harman","year":"1983","journal-title":"Age"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41419-024-06691-w","article-title":"The crosstalk between mitochondrial quality control and metal-dependent cell death","volume":"15","author":"Zhou","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Duvigneau, J.C., Esterbauer, H., and Kozlov, A.V. (2019). Role of heme oxygenase as a modulator of heme-mediated pathways. Antioxidants, 8.","DOI":"10.3390\/antiox8100475"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.bbamcr.2018.12.012","article-title":"Mitochondrial quality control as a key determinant of cell survival","volume":"1866","author":"Sedlackova","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mSphere.00327-17","article-title":"The gut microbiota of apparently healthy aged Chinese is similar to that of the apparently healthy young","volume":"2","author":"Bian","year":"2017","journal-title":"mSphere"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Clark, A., and Mach, N. (2017). The crosstalk between the gut microbiota and mitochondria during exercise. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00319"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.1080\/10408398.2020.1867054","article-title":"Gut microbiota and aging","volume":"62","author":"Ling","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41574-021-00626-7","article-title":"Mitochondrial and metabolic dysfunction in aging and age-related diseases","volume":"18","author":"Amorim","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Salazar, J., Dur\u00e1n, P., D\u00edaz, M.P., Chac\u00edn, M., Santeliz, R., Mengual, E., Guti\u00e9rrez, E., Le\u00f3n, X., D\u00edaz, A., and Bernal, M. (2023). Exploring the relationship between the gut microbiota and aging: A possible age modulator. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20105845"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1136\/gutjnl-2017-315542","article-title":"Age-dependent changes in GI physiology and microbiota: Time to reconsider?","volume":"67","author":"An","year":"2018","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10813","DOI":"10.1007\/s12035-025-04846-0","article-title":"Microbiome Gut-Brain-Axis: Impact on brain development and mental health","volume":"62","author":"Ramadan","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s12035-025-05321-6","article-title":"The Gut\u2013Brain axis in Autism: Inflammatory mechanisms, molecular insights, and emerging Microbiome-Based therapies","volume":"63","author":"Hetta","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.cmet.2023.12.007","article-title":"Human trials exploring anti-aging medicines","volume":"36","author":"Guarente","year":"2024","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1038\/s41591-023-02296-6","article-title":"Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality","volume":"29","author":"Tian","year":"2023","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e200","DOI":"10.1017\/cts.2023.627","article-title":"Age-Friendly research: Promoting inclusion of older adults in clinical and translational research","volume":"7","author":"Lindauer","year":"2023","journal-title":"J. Clin. Transl. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/00005650-199206000-00002","article-title":"The MOS 36-item short-form health survey (SF-36)","volume":"30","author":"Ware","year":"1992","journal-title":"Med. Care"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"The WHOQOL Group (1998). Development of the World Health Organization WHOQOL-BREF quality of life assessment. Psychol. Med., 28, 551\u2013558.","DOI":"10.1017\/S0033291798006667"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in older adults: Evidence for a phenotype","volume":"56","author":"Fried","year":"2001","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1093\/gerona\/62.7.722","article-title":"Frailty in relation to the accumulation of deficits","volume":"62","author":"Rockwood","year":"2007","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lv, J., Zhang, B., Ye, Y., Li, Z., Wang, W., Zhao, Q., Liu, Q., Zhao, Z., Zhang, H., and Wang, B. (2023). Assessment of cardio-renal-hepatic function in patients with valvular heart disease: A multi-biomarker approach\u2014The cardio-renal-hepatic score. BMC Med., 21.","DOI":"10.1186\/s12916-023-02971-y"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Palix, C., Chauveau, L., Felisatti, F., Chocat, A., Coulbault, L., H\u00e9bert, O., M\u00e9zenge, F., Landeau, B., Haudry, S., and Fauvel, S. (2025). Allostatic load, a measure of cumulative physiological stress, impairs brain structure but not \u03b2-accumulation in older adults: An exploratory study. Front. Aging Neurosci., 17.","DOI":"10.3389\/fnagi.2025.1508677"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41598-023-49656-3","article-title":"Comprehensive allostatic load risk index is associated with increased frontal and left parietal white matter hyperintensities in mid-life cognitively healthy adults","volume":"14","author":"Gregory","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_28","unstructured":"Barker, J. (2024). Physic: A Primer of Herbal Medicine, Aeon Books."},{"key":"ref_29","first-page":"2882","article-title":"A Systematic Review for Advanced Solutions for Alcohol Use Disorder: Detection, Treatment, and Prevention","volume":"7","author":"Alshammari","year":"2024","journal-title":"J. Int. Crisis Risk Commun. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, F., Qiao, H., Zheng, Y., Zheng, Y., Ni, Y., and He, X. (2025). Exploring the nonlinear relationship between serum uric acid to high-density lipoprotein cholesterol ratio and obesity in older adults: A cross-sectional study. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1587194"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1080\/14737159.2025.2509027","article-title":"A novel metabolomic aging score-better than conventional metrics in predicting short-term mortality","volume":"25","author":"Liu","year":"2025","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhu, Z., Lyu, J., Hao, X., Guo, H., Zhang, X., He, M., Cheng, X., Cheng, S., and Wang, C. (2024). Estimation of physiological aging based on routine clinical biomarkers: A prospective cohort study in elderly Chinese and the UK Biobank. BMC Med., 22.","DOI":"10.1186\/s12916-024-03769-2"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1093\/gerona\/glaa114","article-title":"The role of psychological and social well-being on physical function trajectories in older adults","volume":"75","author":"Saadeh","year":"2020","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12979-022-00326-4","article-title":"Telomere and mitochondria mediated the association between dietary inflammatory index and mild cognitive impairment: A prospective cohort study","volume":"20","author":"Liu","year":"2023","journal-title":"Immun. Aging"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Maldonado, E., Morales-Pison, S., Urbina, F., and Solari, A. (2023). Aging hallmarks and the role of oxidative stress. Antioxidants, 12.","DOI":"10.3390\/antiox12030651"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e70655","DOI":"10.1096\/fj.202500554R","article-title":"Aerobic Capacity Beyond Cardiorespiratory Fitness Linking Mitochondrial Function, Disease Resilience and apparently healthy aging","volume":"39","author":"Gao","year":"2025","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e35696","DOI":"10.2196\/35696","article-title":"A model for estimating biological age from physiological biomarkers of apparently healthy aging: Cross-sectional study","volume":"5","author":"Husted","year":"2022","journal-title":"JMIR Aging"},{"key":"ref_38","unstructured":"Kang, W. (2021). Physiological, Environmental, and Genetic Influences on Iron Homeostasis. [Ph.D. Thesis, Cornell University]."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1177\/13872877241297111","article-title":"Sleep patterns, global mental status and mortality risk among middle-aged urban adults","volume":"102","author":"Beydoun","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wiemann, J., Krell-Roesch, J., Woll, A., and Boes, K. (2024). Longitudinal association between fitness and metabolic syndrome: A population-based study over 29 years follow-up. BMC Public Health, 24.","DOI":"10.1186\/s12889-024-18448-3"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e8491","DOI":"10.1097\/MD.0000000000008491","article-title":"Association of metabolic syndrome and its components with all-cause and cardiovascular mortality in the elderly","volume":"96","author":"Ju","year":"2017","journal-title":"Medicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1152\/physiol.00021.2024","article-title":"Low-grade chronic inflammation: A shared mechanism for chronic diseases","volume":"40","author":"Cifuentes","year":"2025","journal-title":"Physiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12979-022-00306-8","article-title":"Inflammation and cell-to-cell communication, two related aspects in frailty","volume":"19","author":"Pansarasa","year":"2022","journal-title":"Immun. Aging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s40520-025-03181-7","article-title":"Inflammaging and the sex-frailty paradox","volume":"37","author":"Arosio","year":"2025","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1080\/13607863.2020.1847248","article-title":"Sex differences in mental health among older adults: Investigating time trends and possible risk groups with regard to age, educational level and ethnicity","volume":"25","author":"Sialino","year":"2021","journal-title":"Aging Ment. Health"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.jad.2021.08.109","article-title":"Age and sex trends in depressive symptoms across middle and older adulthood: Comparison of the Canadian Longitudinal Study on aging to American and European cohorts","volume":"295","author":"Best","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e3389","DOI":"10.1002\/smi.3389","article-title":"Exploring the interplay of psychological and biological components of stress response and telomere length in the transition from middle age to late adulthood: A systematic review","volume":"40","author":"Chesak","year":"2024","journal-title":"Stress Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1186\/s12877-023-04168-7","article-title":"Social participation, psychological resilience and depression among widowed older adults in China","volume":"23","author":"Li","year":"2023","journal-title":"BMC Geriatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"964","DOI":"10.5664\/jcsm.9072","article-title":"Sex differences in deterioration of sleep properties associated with aging: A 12-year longitudinal cohort study","volume":"17","author":"Kim","year":"2021","journal-title":"J. Clin. Sleep Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Banerjee, S., and Boro, B. (2022). Analysing the role of sleep quality, functional limitation and depressive symptoms in determining life satisfaction among the older Population in India: A moderated mediation approach. BMC Public Health, 22.","DOI":"10.1186\/s12889-022-14329-9"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Gu, M., Liu, C.C., Hsu, C.C., Lu, C.J., Lee, T.S., Chen, M., and Ho, C.C. (2021). Associations of sleep duration with physical fitness performance and self-perception of health: A cross-sectional study of Taiwanese adults aged 23\u201345. BMC Public Health, 21.","DOI":"10.1186\/s12889-021-10636-9"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e67294","DOI":"10.2196\/67294","article-title":"Detecting Sleep\/Wake Rhythm Disruption Related to Cognition in Older Adults With and Without Mild Cognitive Impairment Using the myRhythmWatch Platform: Feasibility and Correlation Study","volume":"8","author":"Jones","year":"2025","journal-title":"JMIR Aging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eaax7331","DOI":"10.1126\/sciadv.aax7331","article-title":"Sleep fragmentation, microglial aging, and cognitive impairment in adults with and without Alzheimer\u2019s dementia","volume":"5","author":"Kaneshwaran","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Idalino, S.C.C., Canever, J.B., C\u00e2ndido, L.M., Wagner, K.J.P., de Souza Moreira, B., Danielewicz, A.L., and De Avelar, N.C.P. (2023). Association between sleep problems and multimorbidity patterns in older adults. BMC Public Health, 23.","DOI":"10.1186\/s12889-023-15965-5"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Badal, V.D., Vaccariello, E.D., Murray, E.R., Yu, K.E., Knight, R., Jeste, D.V., and Nguyen, T.T. (2020). The gut microbiome, aging, and longevity: A systematic review. Nutrients, 12.","DOI":"10.3390\/nu12123759"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ren, M., Li, H., Fu, Z., and Li, Q. (2021). Succession analysis of gut microbiota structure of participants from long-lived families in Hechi, Guangxi, China. Microorganisms, 9.","DOI":"10.3390\/microorganisms9122524"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ai, X., Huang, C., Liu, Q., Duan, R., Ma, X., Li, L., Shu, Z., Miao, Y., Shen, H., and Lv, Y. (2025). Gut microbiome dynamics and functional shifts in apparently healthy aging: Insights from a metagenomic study. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1629811"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hetta, H.F., Sirag, N., Elfadil, H., Salama, A., Aljadrawi, S.F., Alfaifi, A.J., Alwabisi, A.N., AbuAlhasan, B.M., Alanazi, L.S., and Aljohani, Y.A. (2025). Artificial Sweeteners: A Double-Edged Sword for gut microbiome. Diseases, 13.","DOI":"10.3390\/diseases13040115"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jare.2025.04.018","article-title":"From energy metabolism to mood regulation: The rise of lactate as a therapeutic target","volume":"80","author":"Zhang","year":"2026","journal-title":"J. Adv. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Amiri, P., Hosseini, S.A., Ghaffari, S., Tutunchi, H., Ghaffari, S., Mosharkesh, E., Asghari, S., and Roshanravan, N. (2022). Role of butyrate, a gut microbiota derived metabolite, in cardiovascular diseases: A comprehensive narrative review. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.837509"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41398-017-0089-z","article-title":"Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism","volume":"8","author":"Rose","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Bekebrede, A.F., Deuren, T.V., Gerrits, W.J., Keijer, J., and Boer, V.C.D. (2021). Butyrate alters pyruvate flux and induces lipid accumulation in cultured colonocytes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010937"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhang, S., Ning, R., Zeng, B., Deng, F., Kong, F., Guo, W., Zhao, J., and Li, Y. (2022). Gut microbiota composition and metabolic potential of long-living people in China. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.820108"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1080\/10408398.2024.2369946","article-title":"Current research progress, opportunities, and challenges of Limosillactobacillus reuteri-based probiotic dietary strategies","volume":"65","author":"Wang","year":"2025","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11","DOI":"10.46439\/pathology.1.004","article-title":"Microbiome to dictate the occurrence of neurological disorders","volume":"1","author":"Kaushal","year":"2024","journal-title":"J. Exp. Mol. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2320283","DOI":"10.1080\/19490976.2024.2320283","article-title":"Modulation of chronic obstructive pulmonary disease progression by antioxidant metabolites from Pediococcus pentosaceus: Enhancing gut probiotics abundance and the tryptophan-melatonin pathway","volume":"16","author":"Liu","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ikeyama, N., Ohkuma, M., and Sakamoto, M. (2020). Stress response of Mesosutterella multiformis mediated by nitrate reduction. Microorganisms, 8.","DOI":"10.3390\/microorganisms8122003"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Deng, X., Li, H., Wu, A., He, J., Mao, X., Dai, Z., Tian, G., Cai, J., Tang, J., and Luo, Y. (2025). Composition, Influencing Factors, and Effects on Host Nutrient Metabolism of Fungi in Gastrointestinal Tract of Monogastric Animals. Animals, 15.","DOI":"10.3390\/ani15050710"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e00184-23","DOI":"10.1128\/mmbr.00184-23","article-title":"Vitamin biosynthesis in the gut: Interplay between mammalian host and its resident microbiota","volume":"89","author":"Tarracchini","year":"2025","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"\u00d6nning, G., Montelius, C., Hillman, M., and Larsson, N. (2023). Intake of Lactiplantibacillus plantarum HEAL9 improves cognition in moderately stressed subjects: A randomized controlled study. Nutrients, 15.","DOI":"10.3390\/nu15153466"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11241","DOI":"10.1039\/D1FO01608C","article-title":"Pediococcus acidilactici CCFM6432 mitigates chronic stress-induced anxiety and gut microbial abnormalities","volume":"12","author":"Tian","year":"2021","journal-title":"Food Funct."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sun, Y., Wu, D., Zeng, W., Chen, Y., Guo, M., Lu, B., Li, H., Sun, C., Yang, L., and Jiang, X. (2021). The role of intestinal dysbacteriosis induced arachidonic acid metabolism disorder in inflammaging in atherosclerosis. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.618265"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"104156","DOI":"10.1016\/j.fbio.2024.104156","article-title":"A retrospective study of gut microbiota characteristics in a shanghai elderly cohort of hyperlipidemic patients","volume":"60","author":"Qu","year":"2024","journal-title":"Food Biosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1186\/s12967-022-03801-0","article-title":"Analysis of correlations between gut microbiota, stool short chain fatty acids, calprotectin and cardiometabolic risk factors in postmenopausal women with obesity: A cross-sectional study","volume":"20","author":"Kaczmarczyk","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Sheng, S., Yan, S., Chen, J., Zhang, Y., Wang, Y., Qin, Q., Li, W., Li, T., Huang, M., and Ding, S. (2022). Gut microbiome is associated with metabolic syndrome accompanied by elevated gamma-glutamyl transpeptidase in men. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.946757"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"20220910","DOI":"10.1515\/biol-2022-0910","article-title":"Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects","volume":"19","author":"Lin","year":"2024","journal-title":"Open Life Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s11055-024-01712-9","article-title":"The Role of Interactions along the Brain\u2013Gut\u2013Microbiome Axis in the Regulation of Circadian Rhythms, Sleep Mechanisms, and Their Disorders","volume":"54","author":"Shirolapov","year":"2024","journal-title":"Neurosci. Behav. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Lan, Y., Lu, J., Qiao, G., Mao, X., Zhao, J., Wang, G., Tian, P., and Chen, W. (2023). Bifidobacterium breve CCFM1025 improves sleep quality via regulating the activity of the HPA axis: A randomized clinical trial. Nutrients, 15.","DOI":"10.3390\/nu15214700"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Luo, B., Yu, J., Cheng, Q., He, F., Meng, F., Yu, Y., Xu, C., Wen, X., Hong, L., and Gao, J. (2022). Altered Intestinal Microbiomes and Lipid Metabolism in Patients With Chronic Disorders of Consciousness. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.781148"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"882","DOI":"10.7150\/ijms.90612","article-title":"A chronic stress-induced microbiome perturbation, highly enriched in Ruminococcaceae_UCG-014, promotes colorectal cancer growth and metastasis","volume":"21","author":"Zhao","year":"2024","journal-title":"Int. J. Med. Sci."},{"key":"ref_81","unstructured":"Rodrigues, T.C.V. (2025). Comprehensive Characterization of the Protein Microbial Anti-Inflammatory Molecule (MAM) from the Genus Faecalibacterium Structural, Diversity, and Anti-Inflammatory Implications. [Ph.D. Thesis, Universidade Federal de Minas Gerais]."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2401654","DOI":"10.1080\/19490976.2024.2401654","article-title":"Gut microbial metabolic signatures in diabetes mellitus and potential preventive and therapeutic applications","volume":"16","author":"Cotter","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Pi\u0142ot, M., Dzi\u0119gielewska-G\u0119siak, S., Walkiewicz, K.W., Bednarczyk, M., Waniczek, D., and Muc-Wierzgo\u0144, M. (2025). Gut Microbiota and Metabolic Dysregulation in Elderly Diabetic Patients: Is There a Gender-Specific Effect. J. Clin. Med., 14.","DOI":"10.3390\/jcm14093103"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13099-025-00695-3","article-title":"Chronic hepatitis B virus infection imbalances short-chain fatty acids and amino acids in the liver and gut via microbiota modulation","volume":"17","author":"Zhang","year":"2025","journal-title":"Gut Pathog."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.2147\/NSS.S484377","article-title":"Associations of intermittent hypoxia burden with gut microbiota Dysbiosis in adult patients with obstructive sleep apnea","volume":"16","author":"Guo","year":"2024","journal-title":"Nat. Sci. Sleep"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Mostafavi Abdolmaleky, H., and Zhou, J.R. (2024). Gut microbiota dysbiosis, oxidative stress, inflammation, and epigenetic alterations in metabolic diseases. Antioxidants, 13.","DOI":"10.3390\/antiox13080985"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Diotaiuti, P., Misiti, F., Marotta, G., Falese, L., Calabr\u00f2, G.E., and Mancone, S. (2025). The Gut Microbiome and Its Impact on Mood and Decision-Making: A Mechanistic and Therapeutic Review. Nutrients, 17.","DOI":"10.3390\/nu17213350"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Sejbuk, M., Siebieszuk, A., and Witkowska, A.M. (2024). The role of gut microbiome in sleep quality and health: Dietary strategies for microbiota support. Nutrients, 16.","DOI":"10.3390\/nu16142259"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Verhoog, S., Taneri, P.E., Roa D\u00edaz, Z.M., Marques-Vidal, P., Troup, J.P., Bally, L., Franco, O.H., Glisic, M., and Muka, T. (2019). Dietary factors and modulation of bacteria strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: A systematic review. Nutrients, 11.","DOI":"10.3390\/nu11071565"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"115018","DOI":"10.1016\/j.celrep.2024.115018","article-title":"Genomic features and prevalence of Ruminococcus species in humans are associated with age, lifestyle, and disease","volume":"43","author":"Valentino","year":"2024","journal-title":"Cell Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.1007\/s10238-023-01161-7","article-title":"Alterations of the intestinal microbiome and metabolome in women with rheumatoid arthritis","volume":"23","author":"Yun","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Fukui, H. (2019). Role of gut dysbiosis in liver diseases: What have we learned so far?. Diseases, 7.","DOI":"10.3390\/diseases7040058"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zhang, D., Leitman, M., Pawar, S., Shera, S., Hernandez, L., Jacobs, J.P., and Dong, T.S. (2025). The Association Between Prevotella copri and Advanced Fibrosis in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease. Nutrients, 17.","DOI":"10.3390\/nu17132145"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1038\/s41591-025-03788-3","article-title":"AI-driven multi-omics modeling of myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"31","author":"Xiong","year":"2025","journal-title":"Nat. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"115568","DOI":"10.1016\/j.biopha.2023.115568","article-title":"Faecalibacterium prausnitzii, Bacteroides faecis and Roseburia intestinalis attenuate clinical symptoms of experimental colitis by regulating Treg\/Th17 cell balance and intestinal barrier integrity","volume":"167","author":"Mohebali","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2395092","DOI":"10.1080\/19490976.2024.2395092","article-title":"Effects of postbiotics on chronic diarrhea in young adults: A randomized, double-blind, placebo-controlled crossover trial assessing clinical symptoms, gut microbiota, and metabolite profiles","volume":"16","author":"Guo","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1017\/gmb.2023.14","article-title":"The butyrate-producing and spore-forming bacterial genus Coprococcus as a potential biomarker for neurological disorders","volume":"4","author":"Notting","year":"2023","journal-title":"Gut Microbiome"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41580-019-0173-8","article-title":"Mitochondria as multifaceted regulators of cell death","volume":"21","author":"Bock","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/9\/2097\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:46:45Z","timestamp":1789987605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/9\/2097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,19]]},"references-count":98,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["microorganisms14092097"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14092097","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,19]]}}}