Sarcopenia, characterized by skeletal muscle atrophy, was previously considered age-related; however, it is also associated with other diseases. Nonalcoholic fatty liver disease (NAFLD) is known to cause sarcopenia, and its complications have been reported to affect prognosis. The intestinal microbiota of patients with NAFLD or sarcopenia has been found to be altered compared to that of healthy individuals. However, the alterations that occur when both diseases coexist in humans or experimental animals remain unclear. Therefore, this study aimed to determine the intestinal microbiota changes associated with NAFLD with sarcopenia in SHRSP5/Dmcr rats at the time of concomitant disease. Fecal samples were collected from the rectum of SHRSP5/Dmcr rats fed a normal diet (non-NAFLD and non-Sarcopenia, n = 5) or a high-fat and high-cholesterol diet (NAFLD and Sarcopenia, n = 5) for 20 weeks, and subjected to 16S rRNA analysis. In the NAFLD and sarcopenia group, the diversity of the intestinal microbiota was reduced; further, the bacterial species reported in patients with NAFLD or sarcopenia were also changed. At the family level, the abundances of Akkermansiaceae, Bacteroidaceae, and Tannerellaceae were significantly higher whereas Ruminococcaceae and Lactobacillaceae were decreased in the NAFLD and sarcopenia group. At the genus level, the abundances of Akkermansia, Bacteroides, Ruminococcus, and Parabacteroides were significantly higher whereas the abundance of Lactobacillus was significantly decreased in the NAFLD and sarcopenia group. Overall, these findings help improve the existing understanding regarding the intestinal microbiota changes observed in conditions where NASH and sarcopenia co-occur.

College of Human Life and Environment Kinjo Gakuin University 2 1723 Omori Moriyama ku Nagoya shi Aichi 463 8521 Japan

Department of Medical Laboratory Science Faculty of Health Sciences Okayama University 2 5 1 Shikata cho Kita ku Okayama shi Okayama 700 8558 Japan

Department of Medical Laboratory Science Graduate School of Health Sciences Okayama University 2 5 1 Shikata cho Kita ku Okayama shi Okayama 700 8558 Japan

Department of Medical Technology Ehime Prefectural University of Health Sciences 543 Takoda Tobe cho Iyo gun Ehime 791 2101 Japan

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Açar Y, Ağagündüz D, De Cicco P, Capasso R (2023) Flavonoids: their putative neurologic roles, epigenetic changes, and gut microbiota alterations in Parkinson’s disease. Biomed Pharmacother 168:115788. https://doi.org/10.1016/j.biopha.2023.115788 PubMed DOI

Adak A, Khan MR (2019) An insight into gut microbiota and its functionalities. Cell Mol Life Sci 76(3):473–493. https://doi.org/10.1007/s00018-018-2943-4 PubMed DOI

Ağagündüz D, Çelik E, Cemali Ö, Bingöl FG, Özenir Ç, Özoğul F, Capasso R (2023) Probiotics, live biotherapeutic products (LBPs), and gut-brain axis related psychological conditions: implications for research and dietetics. Probiotics Antimicrob Proteins 15(4):1014–1031. https://doi.org/10.1007/s12602-023-10092-4 PubMed DOI

Bauer J, Morley JE, Schols A, Ferrucci L, Cruz-Jentoft AJ, Dent E, Baracos VE, Crawford JA, Doehner W, Heymsfield SB, Jatoi A, Kalantar-Zadeh K, Lainscak M, Landi F, Laviano A, Mancuso M, Muscaritoli M, Prado CM, Strasser F . . . Anker SD (2019) Sarcopenia: a time for action. An SCWD position paper. J Cachexia Sarcopenia Muscle 10(5):956–961. https://doi.org/10.1002/jcsm.12483

Boursier J, Diehl AM (2015) Implication of gut microbiota in nonalcoholic fatty liver disease. PLoS Pathog 11(1):e1004559. https://doi.org/10.1371/journal.ppat.1004559 PubMed DOI PMC

Boursier J, Mueller O, Barret M, Machado M, Fizanne L, Araujo-Perez F, Guy CD, Seed PC, Rawls JF, David LA, Hunault G, Oberti F, Calès P, Diehl AM (2016) The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 63(3):764–775. https://doi.org/10.1002/hep.28356 PubMed DOI

Chao YW, Tung YT, Yang SC, Shirakawa H, Su LH, Loe PY, Chiu WC (2024) The effects of rice bran on neuroinflammation and gut microbiota in ovariectomized mice fed a drink with fructose. Nutrients 16(17). https://doi.org/10.3390/nu16172980

Christopherson MR, Dawson JA, Stevenson DM, Cunningham AC, Bramhacharya S, Weimer PJ, Kendziorski C, Suen G (2014) Unique aspects of fiber degradation by the ruminal ethanologen Ruminococcus albus 7 revealed by physiological and transcriptomic analysis. BMC Genomics 15(1):1066. https://doi.org/10.1186/1471-2164-15-1066 PubMed DOI PMC

Clemente JC, Ursell LK, Parfrey LW, Knight R (2012) The impact of the gut microbiota on human health: an integrative view. Cell 148(6):1258–1270. https://doi.org/10.1016/j.cell.2012.01.035 PubMed DOI PMC

Collins KH, Paul HA, Hart DA, Reimer RA, Smith IC, Rios JL, Seerattan RA, Herzog W (2016) A high-fat high-sucrose diet rapidly alters muscle integrity, inflammation and gut microbiota in male rats. Sci Rep 6:37278. https://doi.org/10.1038/srep37278 PubMed DOI PMC

Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinková E, Vandewoude M, Zamboni M (2010) Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 39(4):412–423. https://doi.org/10.1093/ageing/afq034 PubMed DOI PMC

De Minicis S, Rychlicki C, Agostinelli L, Saccomanno S, Candelaresi C, Trozzi L, Mingarelli E, Facinelli B, Magi G, Palmieri C, Marzioni M, Benedetti A, Svegliati-Baroni G (2014) Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice. Hepatology 59(5):1738–1749. https://doi.org/10.1002/hep.26695 PubMed DOI

Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A 110(22):9066–9071. https://doi.org/10.1073/pnas.1219451110 PubMed DOI PMC

Fan JG, Kim SU, Wong VW (2017) New trends on obesity and NAFLD in Asia. J Hepatol 67(4):862–873. https://doi.org/10.1016/j.jhep.2017.06.003 PubMed DOI

Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155(7):1451–1463. https://doi.org/10.1016/j.cell.2013.11.024 PubMed DOI PMC

Hsu CS, Kao JH (2018) Sarcopenia and chronic liver diseases. Expert Rev Gastroenterol Hepatol 12(12):1229–1244. https://doi.org/10.1080/17474124.2018.1534586 PubMed DOI

Kang L, Li P, Wang D, Wang T, Hao D, Qu X (2021) Alterations in intestinal microbiota diversity, composition, and function in patients with sarcopenia. Sci Rep 11(1):4628. https://doi.org/10.1038/s41598-021-84031-0 PubMed DOI PMC

Karlsson FH, Tremaroli V, Nookaew I, Bergström G, Behre CJ, Fagerberg B, Nielsen J, Bäckhed F (2013) Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498(7452):99–103. https://doi.org/10.1038/nature12198 PubMed DOI

Kitamori K, Naito H, Tamada H, Kobayashi M, Miyazawa D, Yasui Y, Sonoda K, Tsuchikura S, Yasui N, Ikeda K, Moriya T, Yamori Y, Nakajima T (2012) Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr. Environ Health Prev Med 17(3):173–182. https://doi.org/10.1007/s12199-011-0235-9 PubMed DOI

Koo BK, Kim D, Joo SK, Kim JH, Chang MS, Kim BG, Lee KL, Kim W (2017) Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. J Hepatol 66(1):123–131. https://doi.org/10.1016/j.jhep.2016.08.019 PubMed DOI

Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, Martin P, Philippe C, Walker F, Bado A, Perlemuter G, Cassard-Doulcier AM, Gérard P (2013) Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut 62(12):1787–1794. https://doi.org/10.1136/gutjnl-2012-303816 PubMed DOI

Lee YH, Jung KS, Kim SU, Yoon HJ, Yun YJ, Lee BW, Kang ES, Han KH, Lee HC, Cha BS (2015) Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: nationwide surveys (KNHANES 2008–2011). J Hepatol 63(2):486–493. https://doi.org/10.1016/j.jhep.2015.02.051 PubMed DOI

Liu P, Wu L, Peng G, Han Y, Tang R, Ge J, Zhang L, Jia L, Yue S, Zhou K, Li L, Luo B, Wang B (2019) Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort. Brain Behav Immun 80:633–643. https://doi.org/10.1016/j.bbi.2019.05.008 PubMed DOI

Liu Y, Guo Y, Liu Z, Feng X, Zhou R, He Y, Zhou H, Peng H, Huang Y (2023) Augmented temperature fluctuation aggravates muscular atrophy through the gut microbiota. Nat Commun 14(1):3494. https://doi.org/10.1038/s41467-023-39171-4 PubMed DOI PMC

Loomba R, Seguritan V, Li W, Long T, Klitgord N, Bhatt A, Dulai PS, Caussy C, Bettencourt R, Highlander SK, Jones MB, Sirlin CB, Schnabl B, Brinkac L, Schork N, Chen CH, Brenner DA, Biggs W, Yooseph S, . . . Nelson KE (2017) Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab 25(5):1054–1062.e1055. https://doi.org/10.1016/j.cmet.2017.04.001

Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, McGilvray ID, Allard JP (2013) Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 58(1):120–127. https://doi.org/10.1002/hep.26319 PubMed DOI

Nd AM (2019) Non-alcoholic fatty liver disease, an overview. Integr Med (Encinitas) 18(2):42–49 PubMed

Ni Y, Yang X, Zheng L, Wang Z, Wu L, Jiang J, Yang T, Ma L, Fu Z (2019) Lactobacillus and Bifidobacterium improves physiological function and cognitive ability in aged mice by the regulation of gut microbiota. Mol Nutr Food Res 63(22):e1900603. https://doi.org/10.1002/mnfr.201900603 PubMed DOI

Ninomiya S, Nakamura N, Nakamura H, Mizutani T, Kaneda Y, Yamaguchi K, Matsumoto T, Kitagawa J, Kanemura N, Shiraki M, Hara T, Shimizu M, Tsurumi H (2020) Low levels of serum tryptophan underlie skeletal muscle atrophy. Nutrients 12(4). https://doi.org/10.3390/nu12040978

Nishijima S, Suda W, Oshima K, Kim SW, Hirose Y, Morita H, Hattori M (2016) The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Res 23(2):125–133. https://doi.org/10.1093/dnares/dsw002 PubMed DOI PMC

O’Callaghan J, O’Toole PW (2013) Lactobacillus: host-microbe relationships. Curr Top Microbiol Immunol 358:119–154. https://doi.org/10.1007/82_2011_187 PubMed DOI

Park CH, Lee EJ, Kim HL, Lee YT, Yoon KJ, Kim HN (2022) Sex-specific associations between gut microbiota and skeletal muscle mass in a population-based study. J Cachexia Sarcopenia Muscle 13(6):2908–2919. https://doi.org/10.1002/jcsm.13096 PubMed DOI PMC

Perlin CM, Longo L, Keingeski MB, Picon RV, Álvares-da-Silva MR (2023) Gut mycobiota changes in liver diseases: a systematic review. Med Mycol 61(8). https://doi.org/10.1093/mmy/myad071

Petersen AM, Pedersen BK (2005) The anti-inflammatory effect of exercise. J Appl Physiol (1985) 98(4):1154–1162. https://doi.org/10.1152/japplphysiol.00164.2004

Raman M, Ahmed I, Gillevet PM, Probert CS, Ratcliffe NM, Smith S, Greenwood R, Sikaroodi M, Lam V, Crotty P, Bailey J, Myers RP, Rioux KP (2013) Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 11(7):868–875.e861–863. https://doi.org/10.1016/j.cgh.2013.02.015

Ren X, Hao S, Yang C, Yuan L, Zhou X, Zhao H, Yao J (2021) Alterations of intestinal microbiota in liver cirrhosis with muscle wasting. Nutrition 83:111081. https://doi.org/10.1016/j.nut.2020.111081 PubMed DOI

Rinella ME (2015) Nonalcoholic fatty liver disease: a systematic review. Jama 313(22):2263–2273. https://doi.org/10.1001/jama.2015.5370 PubMed DOI

Russell WR, Duncan SH, Scobbie L, Duncan G, Cantlay L, Calder AG, Anderson SE, Flint HJ (2013) Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol Nutr Food Res 57(3):523–535. https://doi.org/10.1002/mnfr.201200594 PubMed DOI

Saban Güler M, Arslan S, Ağagündüz D, Cerqua I, Pagano E, Berni Canani R, Capasso R (2025) Butyrate: a potential mediator of obesity and microbiome via different mechanisms of actions. Food Res Int 199:115420. https://doi.org/10.1016/j.foodres.2024.115420 PubMed DOI

Sartor RB (2010) Genetics and environmental interactions shape the intestinal microbiome to promote inflammatory bowel disease versus mucosal homeostasis. Gastroenterology 139(6):1816–1819. https://doi.org/10.1053/j.gastro.2010.10.036 PubMed DOI

Schneeberger M, Everard A, Gómez-Valadés AG, Matamoros S, Ramírez S, Delzenne NM, Gomis R, Claret M, Cani PD (2015) Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep 5:16643. https://doi.org/10.1038/srep16643 PubMed DOI PMC

Senior HE, Henwood TR, Beller EM, Mitchell GK, Keogh JW (2015) Prevalence and risk factors of sarcopenia among adults living in nursing homes. Maturitas 82(4):418–423. https://doi.org/10.1016/j.maturitas.2015.08.006 PubMed DOI

Sharon G, Garg N, Debelius J, Knight R, Dorrestein PC, Mazmanian SK (2014) Specialized metabolites from the microbiome in health and disease. Cell Metab 20(5):719–730. https://doi.org/10.1016/j.cmet.2014.10.016 PubMed DOI PMC

Siddharth J, Chakrabarti A, Pannérec A, Karaz S, Morin-Rivron D, Masoodi M, Feige JN, Parkinson SJ (2017) Aging and sarcopenia associate with specific interactions between gut microbes, serum biomarkers and host physiology in rats. Aging (Albany NY) 9(7):1698–1720. https://doi.org/10.18632/aging.101262

Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C (2016) Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol 65(3):589–600. https://doi.org/10.1016/j.jhep.2016.05.013 PubMed DOI

Velayudham A, Dolganiuc A, Ellis M, Petrasek J, Kodys K, Mandrekar P, Szabo G (2009) VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology 49(3):989–997. https://doi.org/10.1002/hep.22711 PubMed DOI

Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, Bendlin BB, Rey FE (2017) Gut microbiome alterations in Alzheimer’s disease. Sci Rep 7(1):13537. https://doi.org/10.1038/s41598-017-13601-y PubMed DOI PMC

Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, Brostoff J, Parkhill J, Dougan G, Petrovska L (2011) High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol 11:7. https://doi.org/10.1186/1471-2180-11-7 PubMed DOI PMC

Wang Y, Zhang Y, Lane NE, Wu J, Yang T, Li J, He H, Wei J, Zeng C, Lei G (2022) Population-based metagenomics analysis reveals altered gut microbiome in sarcopenia: data from the Xiangya Sarcopenia Study. J Cachexia Sarcopenia Muscle 13(5):2340–2351. https://doi.org/10.1002/jcsm.13037 PubMed DOI PMC

Weiss GA, Hennet T (2017) Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci 74(16):2959–2977. https://doi.org/10.1007/s00018-017-2509-x PubMed DOI PMC

Wexler HM (2007) Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev 20(4):593–621. https://doi.org/10.1128/cmr.00008-07 PubMed DOI PMC

Wong VW, Tse CH, Lam TT, Wong GL, Chim AM, Chu WC, Yeung DK, Law PT, Kwan HS, Yu J, Sung JJ, Chan HL (2013) Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis–a longitudinal study. PLoS One 8(4):e62885. https://doi.org/10.1371/journal.pone.0062885 PubMed DOI PMC

Wong VW, Wong GL, Yip GW, Lo AO, Limquiaco J, Chu WC, Chim AM, Yu CM, Yu J, Chan FK, Sung JJ, Chan HL (2011) Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease. Gut 60(12):1721–1727. https://doi.org/10.1136/gut.2011.242016 PubMed DOI

Yamamoto S, Honma K, Fujii M, Kakimoto M, Kirihara S, Nakayama H, Kitamori K, Sato I, Hirohata S, Watanabe S (2023) SHRSP5/Dmcr rats fed a high-fat and high-cholesterol diet develop disease-induced sarcopenia as nonalcoholic steatohepatitis progresses. Ann Anat 249:152104. https://doi.org/10.1016/j.aanat.2023.152104 PubMed DOI

Zhao Y, Li C, Luan Z, Chen J, Wang C, Jing Y, Qi S, Zhao Z, Zhang H, Wu J, Chen Y, Li Z, Zhao B, Wang S, Yang Y, Sun G (2023) Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis. Sci Rep 13(1):12946. https://doi.org/10.1038/s41598-023-38530-x PubMed DOI PMC

Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, Gill SR (2013) Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 57(2):601–609. https://doi.org/10.1002/hep.26093 PubMed DOI