[en] Liver oxygen stress is one of the main extraintestinal manifestations of colitis and 5% of cases develop into a further liver injury and metabolic disease. 2′-fucosyllactose (2′-FL), a main member of human milk oligosaccharides (HMOs), has been found to exert efficient impacts on remitting colitis. However, whether 2′-FL exerts the function to alleviate colitis-induced liver injury and how 2′-FL influences the metabolism via regulating gut microbiota remain unknown. Herein, in our study, liver oxygen stress was measured by measuring liver weight and oxygen-stress-related indicators. Then, 16S full-length sequencing analysis and non-target metabolome in feces were performed to evaluate the overall responses of metabolites and intestinal bacteria after being treated with 2′-FL (400 mg/kg b.w.) in colitis mice. The results showed that, compared with the control group, the liver weight of colitis mice was significantly decreased by 18.30% (p < 0.05). After 2′-FL treatment, the liver weight was significantly increased by 12.65% compared with colitis mice (p < 0.05). Meanwhile, they exhibited higher levels of oxidation in liver tissue with decreasing total antioxidant capacity (T-AOC) (decreased by 17.15%) and glutathione (GSH) levels (dropped by 22.68%) and an increasing malondialdehyde (MDA) level (increased by 36.24%), and 2′-FL treatment could reverse those tendencies. Full-length 16S rRNA sequencing revealed that there were 39 species/genera differentially enriched in the control, dextran sulphate sodium (DSS), and DSS + 2′-FL groups. After treatment with 2′-FL, the intestinal metabolic patterns, especially glycometabolism and the lipid-metabolism-related process, in DSS mice were strikingly altered with 33 metabolites significantly down-regulated and 26 metabolites up-regulated. Further analysis found DSS induced a 40.01%, 41.12%, 43.81%, and 39.86% decline in acetic acid, propionic acid, butyric acid, and total short chain fatty acids (SCFAs) in colitis mice (all p < 0.05), respectively, while these were up-regulated to different degrees in the DSS + 2′-FL group. By co-analyzing the data of gut microbiota and metabolites, glycometabolism and lipid-metabolism-associated metabolites exhibited strong positive/negative relationships with Akkermansia_muciniphila (all p < 0.01) and Paraprevotella spp. (all p < 0.01), suggesting that the two species might play crucial roles in the process of 2′-FL alleviating colitis-induced liver oxygen stress. In conclusion, in the gut−liver−microbiotas axis, 2′-FL mediated in glucose and lipid-related metabolism and alleviated liver oxygen stress via regulating gut microbiota in the DSS-induced colitis model. The above results provide a new perspective to understand the probiotic function of 2′-FL.
Disciplines :
Food science
Author, co-author :
Yao, Qianqian ; Université de Liège - ULiège > TERRA Research Centre ; Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, 2# Yuanmingyuan West Road, Haidian District, Beijing 100193, China ; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
Gao, Yanan; Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, 2# Yuanmingyuan West Road, Haidian District, Beijing 100193, China ; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
Critical editor :
Wang, Jiaqi; Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, 2# Yuanmingyuan West Road, Haidian District, Beijing 100193, China ; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
Zheng, Nan; Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, 2# Yuanmingyuan West Road, Haidian District, Beijing 100193, China ; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
Other collaborator :
Fan, Linlin; Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, 2# Yuanmingyuan West Road, Haidian District, Beijing 100193, China ; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
Language :
English
Title :
2'-Fucosyllactose Remits Colitis-Induced Liver Oxygen Stress through the Gut-Liver-Metabolites Axis.
This research was funded by Scientific Research Project for Major Achievements of Ministry of Modern Agro-Industry Tech-nology Research System of China (grant number CARS-36) and the Agricultural Science and Technology Innovation Program (grant number ASTIP-IAS12).
Zuo T. Kamm M.A. Colombel J.F. Ng S.C. Urbanization and the gut microbiota in health and inflammatory bowel disease Gastroenterol. Hepatol. 2018 15 440 452 10.1038/s41575-018-0003-z
Vavricka S.R. Schoepfer A. Scharl M. Lakatos P.L. Navarini A. Rogler G. Extraintestinal manifestations of inflammatory bowel disease Inflamm. Bowel Dis. 2015 21 1982 1992 10.1097/MIB.0000000000000392
Wu Z. Liu X. Huang S. Li T. Zhang X. Pang J. Zhao J. Chen L. Zhang B. Wang J. et al. Milk Fat Globule Membrane attenuates acute colitis and secondary liver injury by improving the mucus barrier and regulating the gut microbiota Front. Immunol. 2022 13 865273 10.3389/fimmu.2022.865273
Rojas-Feria M. Castro M. Suárez E. Ampuero J. Romero-Gómez M. Hepatobiliary manifestations in inflammatory bowel disease: The gut, the drugs and the liver World J. Gastroenterol. 2013 19 7327 7340 10.3748/wjg.v19.i42.7327 24259964
Chao C.-Y. Battat R. Al Khoury A. Restellini S. Sebastiani G. Bessissow T. Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article World J. Gastroenterol. 2016 22 7727 7734 10.3748/wjg.v22.i34.7727
Rogler G. Singh A. Kavanaugh A. Rubin D.T. Extraintestinal manifestations of inflammatory bowel disease: Current concepts, treatment, and implications for disease management Gastroenterology 2021 161 1118 1132 10.1053/j.gastro.2021.07.042
Ohtani N. Kawada N. Role of the gut-liver axis in liver inflammation, fibrosis, and cancer: A special focus on the gut microbiota relationship Hepatol. Commun. 2019 3 456 470 10.1002/hep4.1331 30976737
Franzosa E.A. Sirota-Madi A. Avila-Pacheco J. Fornelos N. Haiser H.J. Reinker S. Vatanen T. Hall A.B. Mallick H. McIver L.J. et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease Nat. Microbiol. 2019 4 293 305 10.1038/s41564-018-0306-4
Ip S. Chung M. Raman G. Chew P. Magula N. DeVine D. Trikalinos T. Lau J. Breastfeeding and maternal and infant health outcomes in developed countries Evid. Rep./Technol. Assess. 2007 153 181 186
Zhou J. Shukla V.V. John D. Chen C. Human milk feeding as a protective factor for retinopathy of prematurity: A meta-analysis Pediatrics 2015 136 1576 1586 10.1542/peds.2015-2372
Gabrielli O. Zampini L. Galeazzi T. Padella L. Santoro L. Peila C. Giuliani F. Bertino E. Fabris C. Coppa G.V. Preterm milk oligosaccharides during the first month of lactation Pediatrics 2011 128 e1520 e1531 10.1542/peds.2011-1206
Gopal P.K. Gill H.S. Oligosaccharides and glycoconjugates in bovine milk and colostrum Br. J. Nutr. 2000 84 S69 S74 10.1017/S0007114500002270
Zivkovic A.M. German J.B. Lebrilla C.B. Mills D.A. Human milk glycobiome and its impact on the infant gastrointestinal microbiota Proc. Natl. Acad. Sci. USA 2011 108 (Suppl. 1) 4653 4658 10.1073/pnas.1000083107
Cheng L. Kong C. Walvoort M. Faas M.M. de Vos P. Human milk oligosaccharides differently modulate goblet cells under homeostatic, proinflammatory conditions and ER stress Mol. Nutr. Food Res. 2020 64 e1900976 10.1002/mnfr.201900976 31800974
Smilowitz J.T. O’Sullivan A. Barile D. German J.B. Lönnerdal B. Slupsky C.M. The human milk metabolome reveals diverse oligosaccharide profiles J. Nutr. 2013 143 1709 1718 10.3945/jn.113.178772
Thurl S. Munzert M. Henker J. Boehm G. Müller-Werner B. Jelinek J. Stahl B. Variation of human milk oligosaccharides in relation to milk groups and lactational periods Br. J. Nutr. 2010 104 1261 1271 10.1017/S0007114510002072 20522272
Sprenger N. Lee L.Y. De Castro C.A. Steenhout P. Thakkar S.K. Longitudinal change of selected human milk oligosaccharides and association to infants’ growth, an observatory, single center, longitudinal cohort study PLoS ONE 2017 12 e0171814 10.1371/journal.pone.0171814
Dedon L.R. Özcan E. Rani A. Sela D.A. Bifidobacterium infantis metabolizes 2′Fucosyllactose-derived and free fucose through a common catabolic pathway resulting in 1,2-propanediol secretion Front. Nutr. 2020 7 583397 10.3389/fnut.2020.583397 33330584
Salli K. Hirvonen J. Siitonen J. Ahonen I. Anglenius H. Maukonen J. Selective utilization of the human milk oligosaccharides 2′-fucosyllactose, 3-fucosyllactose, and difucosyllactose by various probiotic and pathogenic bacteria J. Agric. Food Chem. 2021 69 170 182 10.1021/acs.jafc.0c06041
Yu Z.-T. Chen C. Newburg D.S. Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes Glycobiology 2013 23 1281 1292 10.1093/glycob/cwt065
Yu Z.-T. Nanthakumar N.N. Newburg D.S. The human milk oligosaccharide 2′-fucosyllactose quenches Campylobacter jejuni-induced inflammation in human epithelial cells HEp-2 and HT-29 and in mouse intestinal mucosa J. Nutr. 2016 146 1980 1990 10.3945/jn.116.230706 27629573
Holscher H.D. Davis S.R. Tappenden K.A. Human milk oligosaccharides influence maturation of human intestinal Caco-2Bbe and HT-29 cell lines J. Nutr. 2014 144 586 591 10.3945/jn.113.189704 24572036
He Y. Liu S. Kling D.E. Leone S. Lawlor N.T. Huang Y. Feinberg S.B. Hill D.R. Newburg D.S. The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation Gut 2016 65 33 46 10.1136/gutjnl-2014-307544 25431457
Li A. Ni W. Li Y. Zhang X. Yang J. Ma X. Jia X. Liu C. Liu L. Effect of 2′-fucosyllactose supplementation on intestinal flora in mice with intestinal inflammatory diseases Int. Dairy J. 2020 110 104797 10.1016/j.idairyj.2020.104797
Yao Q. Fan L. Zheng N. Blecker C. Delcenserie V. Li H. Wang J. 2′-fucosyllactose ameliorates inflammatory bowel disease by modulating gut microbiota and promoting MUC2 expression Front. Nutr. 2022 9 822020 10.3389/fnut.2022.822020
Yao C. Wang Z. Jiang H. Yan R. Huang Q. Wang Y. Xie H. Zou Y. Yu Y. Lv L. Ganoderma lucidum promotes sleep through a gut microbiota-dependent and serotonin-involved pathway in mice Sci. Rep. 2021 11 13660 10.1038/s41598-021-92913-6
Sabino J. Vieira-Silva S. Machiels K. Joossens M. Falony G. Ballet V. Ferrante M. Van Assche G. Van der Merwe S. Vermeire S. et al. Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD Gut 2016 65 1681 1689 10.1136/gutjnl-2015-311004
Tahvilian N. Masoodi M. Faghihi Kashani A. Vafa M. Aryaeian N. Heydarian A. Hosseini A. Moradi N. Farsi F. Effects of saffron supplementation on oxidative/antioxidant status and severity of disease in ulcerative colitis patients: A randomized, double-blind, placebo-controlled study Phytother. Res. 2021 35 946 953 10.1002/ptr.6848
Biswas S.K. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid. Med. Cell. Longev. 2016 2016 5698931 10.1155/2016/5698931
Gnoth M.J. Kunz C. Kinne-Saffran E. Rudloff S. Human milk oligosaccharides are minimally digested in vitro J. Nutr. 2000 130 3014 3020 10.1093/jn/130.12.3014
Rudloff S. Pohlentz G. Borsch C. Lentze M.J. Kunz C. Urinary excretion of in vivo ¹³C-labelled milk oligosaccharides in breastfed infants J. Nutr. 2012 107 957 963 10.1017/S0007114511004016 21888740
Ruhaak L.R. Stroble C. Underwood M.A. Lebrilla C.B. Detection of milk oligosaccharides in plasma of infants Anal. Bioanal. Chem. 2014 406 5775 5784 10.1007/s00216-014-8025-z 25059723
Goehring K.C. Kennedy A.D. Prieto P.A. Buck R.H. Direct evidence for the presence of human milk oligosaccharides in the circulation of breastfed infants PLoS ONE 2014 9 e101692 10.1371/journal.pone.0101692 24999728
Garrido D. Ruiz-Moyano S. Kirmiz N. Davis J.C. Totten S.M. Lemay D.G. Ugalde J.A. German J.B. Lebrilla C.B. Mills D.A. A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596 Sci. Rep. 2016 6 35045 10.1038/srep35045 27756904
Davis J.C. Lewis Z.T. Krishnan S. Bernstein R.M. Moore S.E. Prentice A.M. Mills D.A. Lebrilla C.B. Zivkovic A.M. Growth and morbidity of gambian infants are influenced by maternal milk oligosaccharides and infant gut microbiota Sci. Rep. 2017 7 40466 10.1038/srep40466 28079170
Wu G.D. Chen J. Hoffmann C. Bittinger K. Chen Y.-Y. Keilbaugh S.A. Bewtra M. Knights D. Walters W.A. Knight R. et al. Linking long-term dietary patterns with gut microbial enterotypes Science 2011 334 105 108 10.1126/science.1208344 21885731
Poznyak A. Grechko A.V. Poggio P. Myasoedova V.A. Alfieri V. Orekhov A.N. The diabetes mellitus-atherosclerosis connection: The role of lipid and glucose metabolism and chronic inflammation Int. J. Mol. Sci. 2020 21 1835 10.3390/ijms21051835
Berbudi A. Rahmadika N. Tjahjadi A.I. Ruslami R. Type 2 diabetes and its impact on the immune system Curr. Diabetes Rev. 2020 16 442 449 10.2174/1573399815666191024085838
Nguyen T.T. Brown S. Fedorov A.A. Fedorov E.V. Babbitt P.C. Almo S.C. Raushel F.M. At the periphery of the amidohydrolase superfamily: Bh0493 from Bacillus halodurans catalyzes the isomerization of D-galacturonate to D-tagaturonate Biochemistry 2008 47 1194 1206 10.1021/bi7017738
Chun B.H. Kim K.H. Jeong S.E. Jeon C.O. Genomic and metabolic features of the Bacillus amyloliquefaciens group—B. amyloliquefaciens, B. velezensis, and B. siamensis—Revealed by pan-genome analysis Food Microbiol. 2019 77 146 157 10.1016/j.fm.2018.09.001
Becker D.J. Lowe J.B. Fucose: Biosynthesis and biological function in mammals Glycobiology 2003 13 41R 53R 10.1093/glycob/cwg054 12651883
van Poelje P.D. Potter S.C. Erion M.D. Fructose-1, 6-bisphosphatase inhibitors for reducing excessive endogenous glucose production in type 2 diabetes Handb. Exp. Pharmacol. 2011 203 279 301 10.1007/978-3-642-17214-4_12
Liu Q. Zhang F.-G. Zhang W.-S. Pan A. Yang Y.-L. Liu J.-F. Li P. Liu B.-L. Qi L.-W. Ginsenoside Rg1 Inhibits glucagon-induced hepatic gluconeogenesis through Akt-FoxO1 interaction Theranostics 2017 7 4001 4012 10.7150/thno.18788
Park Y.B. Lee S.K. Lee W.K. Suh C.H. Lee C.W. Lee C.H. Song C.H. Lee J. Lipid profiles in untreated patients with rheumatoid arthritis J. Rheumatol. 1999 26 1701 1704
Olsvik P.A. Skjærven K.H. Søfteland L. Metabolic signatures of bisphenol A and genistein in Atlantic salmon liver cells Chemosphere 2017 189 730 743 10.1016/j.chemosphere.2017.09.076 28988043
Yu J. Zhang H. Li Y. Sun S. Gao J. Zhong Y. Sun D. Zhang G. Metabolomics revealed the toxicity of cationic liposomes in HepG2 cells using UHPLC-Q-TOF/MS and multivariate data analysis Biomed. Chromatogr. 2017 31 e4036 10.1002/bmc.4036 28664536
Park K.S. Lee H.Y. Lee S.Y. Kim M.-K. Kim S.D. Kim J.M. Yun J. Im D.-S. Bae Y.-S. Lysophosphatidylethanolamine stimulates chemotactic migration and cellular invasion in SK-OV3 human ovarian cancer cells: Involvement of pertussis toxin-sensitive G-protein coupled receptor FEBS Lett. 2007 581 4411 4416 10.1016/j.febslet.2007.08.014
