Galactooligosaccharides and Limosilactobacillus reuteri synergistically alleviate gut inflammation and barrier dysfunction by enriching Bacteroides acidifaciens for pentadecanoic acid biosynthesis.
Animals
Humans
Oligosaccharides
/ pharmacology
Mice
Limosilactobacillus reuteri
/ metabolism
Bacteroides
/ drug effects
Synbiotics
/ administration & dosage
Swine
Disease Models, Animal
Colitis, Ulcerative
/ microbiology
Gastrointestinal Microbiome
/ drug effects
Mice, Inbred C57BL
Feces
/ microbiology
Male
NF-kappa B
/ metabolism
Inflammation
/ metabolism
Tight Junctions
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
16
02
2024
accepted:
01
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-κB activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders.
Identifiants
pubmed: 39468026
doi: 10.1038/s41467-024-53144-1
pii: 10.1038/s41467-024-53144-1
doi:
Substances chimiques
Oligosaccharides
0
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9291Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32125036, 32330100,
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32172750
Organisme : Earmarked Fund for China Agriculture Research System
ID : CARS-35
Organisme : China Postdoctoral Science Foundation
ID : 2022M723423
Informations de copyright
© 2024. The Author(s).
Références
Kobayashi, T. et al. Ulcerative colitis. Nat. Rev. Dis. Primers 6, 74 (2020).
pubmed: 32913180
doi: 10.1038/s41572-020-0205-x
Zhang, Y. Z. & Li, Y. Y. Inflammatory bowel disease: pathogenesis. World J. Gastroenterol. 20, 91–99 (2014).
pubmed: 24415861
pmcid: 3886036
doi: 10.3748/wjg.v20.i1.91
Andersen, A. D. et al. Synbiotics combined with glutamine stimulate brain development and the immune system in preterm pigs. J. Nutr. 149, 36–45 (2019).
pubmed: 30608604
doi: 10.1093/jn/nxy243
Kolida, S. & Gibson, G. R. Synbiotics in health and disease. Annu. Rev. Food Sci. Technol. 2, 373–393 (2011).
pubmed: 22129388
doi: 10.1146/annurev-food-022510-133739
Ma, L. et al. Anti-Inflammatory Effect of clostridium butyricum-derived extracellular vesicles in Ulcerative Colitis: Impact on host microRNAs expressions and gut microbiome profiles. Mol. Nutr. Food Res. 67, e2200884 (2023).
pubmed: 37183784
doi: 10.1002/mnfr.202200884
Mu, Q., Tavella, V. J. & Luo, X. M. Role of Lactobacillus reuteri in human health and diseases. Front. Microbiol. 9, 757 (2018).
pubmed: 29725324
pmcid: 5917019
doi: 10.3389/fmicb.2018.00757
Wang, J., Tian, S., Yu, H., Wang, J. & Zhu, W. Response of colonic mucosa-associated microbiota composition, mucosal immune homeostasis, and barrier function to early life galactooligosaccharides intervention in suckling piglets. J. Agric. Food Chem. 67, 578–588 (2019).
pubmed: 30562014
doi: 10.1021/acs.jafc.8b05679
Wu, Y. et al. Strain specificity of lactobacilli with promoted colonization by galactooligosaccharides administration in protecting intestinal barriers during Salmonella infection. J. Adv. Res. 56, 1–14 (2024).
pubmed: 36894120
doi: 10.1016/j.jare.2023.03.001
Rattanaprasert, M. et al. Genes involved in galactooligosaccharide metabolism in Lactobacillus reuteri and their ecological role in the gastrointestinal tract. Appl. Environ. Microb. 85, e01788–01719 (2019).
doi: 10.1128/AEM.01788-19
Li, Z., Liu, H., Xu, B. & Wang, Y. Enterotoxigenic Escherichia coli interferes FATP4-dependent long-chain fatty acid uptake of intestinal epithelial enterocytes via phosphorylation of ERK1/2-PPARγ pathway. Front. Physiol. 10, 798 (2019).
pubmed: 31281267
pmcid: 6596317
doi: 10.3389/fphys.2019.00798
Lin, M. H. et al. Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols. Sci. Rep. 9, 13254 (2019).
pubmed: 31519952
pmcid: 6744566
doi: 10.1038/s41598-019-49684-y
Franzosa, E. A. et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat. Microbiol. 4, 293–305 (2018).
pubmed: 30531976
pmcid: 6342642
doi: 10.1038/s41564-018-0306-4
Weng, Y. J. et al. Correlation of diet, microbiota and metabolite networks in inflammatory bowel disease. J. Dig. Dis. 20, 447–459 (2019).
pubmed: 31240835
doi: 10.1111/1751-2980.12795
Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).
pubmed: 31142855
pmcid: 6650278
doi: 10.1038/s41586-019-1237-9
Di’Narzo, A. F. et al. Integrative analysis of the inflammatory bowel sisease serum metabolome improves our understanding of genetic etiology and points to novel putative therapeutic targets. Gastroenterology 162, 828–843.e811 (2022).
pubmed: 34780722
doi: 10.1053/j.gastro.2021.11.015
Diab, J. et al. Lipidomics in Ulcerative Colitis reveal alteration in mucosal lipid composition associated with the disease state. Inflamm. Bowel Dis. 25, 1780–1787 (2019).
pubmed: 31077307
doi: 10.1093/ibd/izz098
Camilleri, M., Madsen, K., Spiller, R., van Meerveld, B. G. & Verne, G. N. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol. Motil. 24, 503–512 (2012).
pubmed: 22583600
pmcid: 5595063
doi: 10.1111/j.1365-2982.2012.01921.x
Salim, S. Y. & Soderholm, J. D. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm. Bowel Dis. 17, 362–381 (2011).
pubmed: 20725949
doi: 10.1002/ibd.21403
Birchenough, G. & Hansson, G. C. Bacteria tell us how to protect our intestine. Cell Host Microbe 22, 3–4 (2017).
pubmed: 28704650
doi: 10.1016/j.chom.2017.06.011
Fan, L. et al. Gut microbiota bridges dietary nutrients and host immunity. Sci. China Life Sci. 66, 2466–2514 (2023).
pubmed: 37286860
doi: 10.1007/s11427-023-2346-1
Yang, J. Y. et al. Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice. Mucosal Immunol. 10, 104–116 (2017).
pubmed: 27118489
doi: 10.1038/mi.2016.42
Wang, H. et al. Bacteroides acidifaciens in the gut plays a protective role against CD95-mediated liver injury. Gut Microbes 14, 2027853 (2022).
pubmed: 35129072
pmcid: 8820816
doi: 10.1080/19490976.2022.2027853
Nakajima, A. et al. A soluble fiber diet increases Bacteroides fragilis group abundance and immunoglobulin A production in the gut. Appl. Environ. Microbiol. 86, e00405–e00420 (2020).
pubmed: 32332136
pmcid: 7301863
doi: 10.1128/AEM.00405-20
Peng, J. et al. Saffron petal, an edible byproduct of Saffron, alleviates dextran sulfate sodium-induced colitis by inhibiting macrophage activation and regulating gut microbiota. J. Agric. Food Chem. 71, 10616–10628 (2023).
pubmed: 37403229
doi: 10.1021/acs.jafc.2c07915
Zheng, C. et al. Bacteroides acidifaciens and its derived extracellular vesicles improve DSS-induced colitis. Front Microbiol. 14, 1304232 (2023).
pubmed: 38098663
pmcid: 10720640
doi: 10.3389/fmicb.2023.1304232
Yan, D. et al. Fatty acids and lipid mediators in inflammatory bowel disease: From mechanism to treatment. Front. Immunol. 14, 1286667 (2023).
pubmed: 37868958
pmcid: 10585177
doi: 10.3389/fimmu.2023.1286667
Brown, E. M., Clardy, J. & Xavier, R. J. Gut microbiome lipid metabolism and its impact on host physiology. Cell Host Microbe 31, 173–186 (2023).
pubmed: 36758518
pmcid: 10124142
doi: 10.1016/j.chom.2023.01.009
Heimerl, S. et al. Alterations in intestinal fatty acid metabolism in inflammatory bowel disease. Biochim. Biophys. Acta 1762, 341–350 (2006).
pubmed: 16439103
doi: 10.1016/j.bbadis.2005.12.006
Ma, C., Vasu, R. & Zhang, H. The role of long-chain fatty acids in inflammatory bowel disease. Mediators Inflamm. 2019, 8495913 (2019).
pubmed: 31780872
pmcid: 6874876
doi: 10.1155/2019/8495913
Ediriweera, M. K., To, N. B., Lim, Y. & Cho, S. K. Odd-chain fatty acids as novel histone deacetylase 6 (HDAC6) inhibitors. Biochimie 186, 147–156 (2021).
pubmed: 33965456
doi: 10.1016/j.biochi.2021.04.011
Venn-Watson, S., Lumpkin, R. & Dennis, E. A. Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: Could it be essential? Sci. Rep. 10, 8161 (2020).
pubmed: 32424181
pmcid: 7235264
doi: 10.1038/s41598-020-64960-y
Fu, W. et al. Pentadecanoic acid promotes basal and insulin-stimulated glucose uptake in C2C12 myotubes. Food Nutr. Res. 65, 4527 (2021).
doi: 10.29219/fnr.v65.4527
To, N. B., Truong, V. N., Ediriweera, M. K. & Cho, S. K. Effects of combined pentadecanoic acid and tamoxifen treatment on tamoxifen resistance in MCF-7/SC breast cancer cells. Int. J. Mol. Sci. 23, 11340 (2022).
pubmed: 36232636
pmcid: 9570034
doi: 10.3390/ijms231911340
Venn-Watson, S. K. & Butterworth, C. N. Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems. PLoS One 17, e0268778 (2022).
pubmed: 35617322
pmcid: 9135213
doi: 10.1371/journal.pone.0268778
To, N. B., Nguyen, Y. T., Moon, J. Y., Ediriweera, M. K. & Cho, S. K. Pentadecanoic acid, an odd-chain fatty acid, suppresses the stemness of MCF-7/SC human breast cancer stem-like cells through JAK2/STAT3 signaling. Nutrients 12, 1663 (2020).
pubmed: 32503225
pmcid: 7352840
doi: 10.3390/nu12061663
Christian, F., Smith, E. L. & Carmody, R. J. The regulation of NF-κB subunits by phosphorylation. Cells 5, 12 (2016).
pubmed: 26999213
pmcid: 4810097
doi: 10.3390/cells5010012
Park, M. H. & Hong, J. T. Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cells 5, 15 (2016).
pubmed: 27043634
pmcid: 4931664
doi: 10.3390/cells5020015
Taniguchi, K. & Karin, M. NF-κB, inflammation, immunity and cancer: coming of age. Nat. Rev. Immunol. 18, 309–324 (2018).
pubmed: 29379212
doi: 10.1038/nri.2017.142
Prada, M. et al. Association of the odd-chain fatty acid content in lipid groups with type 2 diabetes risk: A targeted analysis of lipidomics data in the EPIC-Potsdam cohort. Clin. Nutr. 40, 4988–4999 (2021).
pubmed: 34364238
doi: 10.1016/j.clnu.2021.06.006
Polonskaya, Y. V. et al. Balance of fatty acids and their correlations with parameters of lipid metabolism and markers of inflammation in men with coronary atherosclerosis. Bull. Exp. Biol. Med. 164, 33–35 (2017).
pubmed: 29119389
doi: 10.1007/s10517-017-3920-x
Stallings, V. A. et al. Diagnosing malabsorption with systemic lipid profiling: pharmacokinetics of pentadecanoic acid and triheptadecanoic acid following oral administration in healthy subjects and subjects with cystic fibrosis. Int. J. Clin. Pharmacol. Ther. 51, 263–273 (2013).
pubmed: 23357842
pmcid: 4350154
doi: 10.5414/CP201793
Jenkins, B. et al. The dietary total-fat content affects the in vivo circulating C15:0 and C17:0 fatty acid levels independently. Nutrients 10, 1646 (2018).
pubmed: 30400275
pmcid: 6266905
doi: 10.3390/nu10111646
Maruyama, C. et al. Differences in serum phospholipid fatty acid compositions and estimated desaturase activities between Japanese men with and without metabolic syndrome. J. Atheroscler. Thromb. 15, 306–313 (2008).
pubmed: 19060426
doi: 10.5551/jat.E564
Yoo, W. et al. Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid. PLoS One 12, e0189965 (2017).
pubmed: 29244873
pmcid: 5731750
doi: 10.1371/journal.pone.0189965
Santaren, I. D. et al. Serum pentadecanoic acid (15:0), a short-term marker of dairy food intake, is inversely associated with incident type 2 diabetes and its underlying disorders. Am. J. Clin. Nutr. 100, 1532–1540 (2014).
pubmed: 25411288
pmcid: 4232018
doi: 10.3945/ajcn.114.092544
Galdiero, E. et al. Pentadecanoic acid against Candida albicans-Klebsiella pneumoniae biofilm: towards the development of an anti-biofilm coating to prevent polymicrobial infections. Res. Microbiol. 172, 103880 (2021).
pubmed: 34563667
doi: 10.1016/j.resmic.2021.103880
Ricciardelli, A. et al. Pentadecanal and pentadecanoic acid coatings reduce biofilm formation of Staphylococcus epidermidis on PDMS. Pathog Dis 78, ftaa012 (2020).
pubmed: 32105313
doi: 10.1093/femspd/ftaa012
Jenkins, B. J. et al. Odd chain fatty acids: New insights of the relationship between the gut microbiota, dietary intake, biosynthesis and glucose intolerance. Sci. Rep. 7, 44845 (2017).
pubmed: 28332596
pmcid: 5362956
doi: 10.1038/srep44845
Dornan, K., Gunenc, A., Oomah, B. D. & Hosseinian, F. Odd chain fatty acids and odd chain phenolic lipids (alkylresorcinols) are essential for diet. J. Am. Oil Chem. Soc. 98, 813–824 (2021).
doi: 10.1002/aocs.12507
Pfeuffer, M. & Jaudszus, A. Pentadecanoic and heptadecanoic acids: Multifaceted odd-chain fatty acids. Adv. Nutr. 7, 730–734 (2016).
pubmed: 27422507
pmcid: 4942867
doi: 10.3945/an.115.011387
Zhang, L., Liang, S., Zong, M., Yang, J. & Lou, W. Microbial synthesis of functional odd-chain fatty acids: A review. World J. Microbiol. Biotechnol. 36, 35 (2020).
pubmed: 32088779
doi: 10.1007/s11274-020-02814-5
Park, Y. K., Dulermo, T., Ledesma-Amaro, R. & Nicaud, J. M. Optimization of odd chain fatty acid production by Yarrowia lipolytica. Biotechnol. Biofuels 11, 158 (2018).
pubmed: 29930704
pmcid: 5991449
doi: 10.1186/s13068-018-1154-4
Rezanka, T., Kolouchova, I. & Sigler, K. Precursor directed biosynthesis of odd-numbered fatty acids by different yeasts. Folia Microbiol. (Praha) 60, 457–464 (2015).
pubmed: 25813199
doi: 10.1007/s12223-015-0388-9
Zhang, L. S. et al. Using 1-propanol to significantly enhance the production of valuable odd-chain fatty acids by Rhodococcus opacus PD630. World J. Microbiol. Biotechnol. 35, 164 (2019).
pubmed: 31637528
doi: 10.1007/s11274-019-2748-0
Wei, W. et al. Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid. Nat. Microbiol. 8, 1534–1548 (2023).
pubmed: 37386075
pmcid: 10390331
doi: 10.1038/s41564-023-01418-7
Qin, N., Li, L., Wang, Z. & Shi, S. Microbial production of odd-chain fatty acids. Biotechnol. Bioeng. 120, 917–931 (2023).
pubmed: 36522132
doi: 10.1002/bit.28308
Wu, H. & San, K. Y. Engineering Escherichia coli for odd straight medium chain free fatty acid production. Appl. Microbiol. Biotechnol. 98, 8145–8154 (2014).
pubmed: 25030454
doi: 10.1007/s00253-014-5882-5
Yamamoto, T., Shimoyama, T., Umegae, S. & Matsumoto, K. Tacrolimus vs. anti-tumour necrosis factor agents for moderately to severely active ulcerative colitis: A retrospective observational study. Aliment. Pharmacol. Ther. 43, 705–716 (2016).
pubmed: 26762838
doi: 10.1111/apt.13531
Torres, J. et al. Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease. Gastroenterology 149, 1716–1730 (2015).
pubmed: 26381892
doi: 10.1053/j.gastro.2015.08.055
Bruscoli, S., Febo, M., Riccardi, C. & Migliorati, G. Glucocorticoid therapy in inflammatory bowel disease: Mechanisms and clinical practice. Front. Immunol. 12, 691480 (2021).
pubmed: 34149734
pmcid: 8209469
doi: 10.3389/fimmu.2021.691480
Ji, Y. et al. Hydroxyproline attenuates dextran sulfate sodium-induced colitis in mice: Involvment of the NF-κB signaling and oxidative stress. Mol. Nutr. Food Res. 62, e1800494 (2018).
pubmed: 30184329
doi: 10.1002/mnfr.201800494
Wu, Y. et al. Maternal galactooligosaccharides supplementation programmed immune defense, microbial colonization and intestinal development in piglets. Food Funct. 12, 7260–7270 (2021).
pubmed: 34165467
doi: 10.1039/D1FO00084E
Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37, 852–857 (2019).
pubmed: 31341288
pmcid: 7015180
doi: 10.1038/s41587-019-0209-9
Noguchi, H., Park, J. & Takagi, T. MetaGene: prokaryotic gene finding from environmental genome shotgun sequences. Nucleic Acids Res. 34, 5623–5630 (2006).
pubmed: 17028096
pmcid: 1636498
doi: 10.1093/nar/gkl723
Li, D., Liu, C. M., Luo, R., Sadakane, K. & Lam, T. W. MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics 31, 1674–1676 (2015).
pubmed: 25609793
doi: 10.1093/bioinformatics/btv033
Fu, L., Niu, B., Zhu, Z., Wu, S. & Li, W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics 28, 3150–3152 (2012).
pubmed: 23060610
pmcid: 3516142
doi: 10.1093/bioinformatics/bts565
Li, R., Li, Y., Kristiansen, K. & Wang, J. SOAP: short oligonucleotide alignment program. Bioinformatics 24, 713–714 (2008).
pubmed: 18227114
doi: 10.1093/bioinformatics/btn025
Buchfink, B., Xie, C. & Huson, D. H. Fast and sensitive protein alignment using DIAMOND. Nat. Methods 12, 59–60 (2015).
pubmed: 25402007
doi: 10.1038/nmeth.3176
Wick, R. R., Judd, L. M., Gorrie, C. L. & Holt, K. E. Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput. Biol. 13, e1005595 (2017).
pubmed: 28594827
pmcid: 5481147
doi: 10.1371/journal.pcbi.1005595
Weiss, A. S. et al. In vitro interaction network of a synthetic gut bacterial community. ISME J 16, 1095–1109 (2022).
pubmed: 34857933
doi: 10.1038/s41396-021-01153-z
Ning, L. et al. Microbiome and metabolome features in inflammatory bowel disease via multi-omics integration analyses across cohorts. Nat. Commun. 14, 7135 (2023).
pubmed: 37932270
pmcid: 10628233
doi: 10.1038/s41467-023-42788-0
Xie, G. et al. A metabolite array technology for precision medicine. Anal. Chem. 93, 5709–5717 (2021).
pubmed: 33797874
doi: 10.1021/acs.analchem.0c04686
Weiss, G. A. et al. Intestinal inflammation alters mucosal carbohydrate foraging and monosaccharide incorporation into microbial glycans. Cell. Microbiol. 23, e13269 (2021).
pubmed: 32975882
doi: 10.1111/cmi.13269
Chen, S., Zhou, Y., Chen, Y. & Gu, J. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34, i884–i890 (2018).
pubmed: 30423086
pmcid: 6129281
doi: 10.1093/bioinformatics/bty560
Xie, C. et al. KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Res. 39, W316–W322 (2011).
pubmed: 21715386
pmcid: 3125809
doi: 10.1093/nar/gkr483
Li, J. et al. Limosilactobacillus johnsoni and Limosilactobacillus mucosae and their extracellular vesicles alleviate gut inflammatory injury by mediating macrophage polarization in a lipopolysaccharide-challenged piglet model. J. Nutr. 153, 2497–2511 (2023).
pubmed: 37343627
doi: 10.1016/j.tjnut.2023.06.009