{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:35:01Z","timestamp":1791923701632,"version":"4.3.4"},"reference-count":116,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o","award":["FAPEMA APP-12327\/22"],"award-info":[{"award-number":["FAPEMA APP-12327\/22"]}]},{"name":"CAPES\u2014Coordination for the Improvement of Higher Education Personnel","award":["001"],"award-info":[{"award-number":["001"]}]},{"DOI":"10.13039\/501100003593","name":"CNPq\u2014National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["317186\/2023-0"],"award-info":[{"award-number":["317186\/2023-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FitoAmaz\u00f4nia Research Network","award":["445615\/2024-9"],"award-info":[{"award-number":["445615\/2024-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Prebiotics, which are non-digestible compounds that selectively modulate gut microbiota, are recognized for their potential to promote host health. Although their bifidogenic effect is well documented, a systematic synthesis of how this microbial modulation translates into clinical gastrointestinal (GI) and metabolic outcomes across diverse populations is needed. This review aims to integrate mechanistic insights with clinical evidence to elucidate the pathway from prebiotic structures to tangible health benefits. Methods: This comprehensive narrative review details the structural properties of major prebiotics (e.g., inulin, FOS, and GOS) that govern their fermentation and the production of short-chain fatty acids (SCFAs). To evaluate clinical efficacy, an analysis of 22 randomized controlled trials from the past decade was conducted, focusing on human studies that utilized ISAPP-recognized prebiotics as the sole intervention. Results: The analysis confirms that prebiotic supplementation consistently increased the abundance of beneficial bacteria (e.g., Bifidobacterium and Lactobacillus) and SCFA production. These changes are associated with significant clinical improvements, including enhanced stool frequency and consistency, strengthened intestinal barrier function, and modulated immune responses. Benefits have been documented in healthy individuals, children, the elderly, and those with conditions such as constipation, metabolic syndrome, and antibiotic-associated dysbiosis. However, significant inter-individual variability in response was evident, and the study designs showed notable heterogeneity in prebiotic type, dosage, and duration. Conclusions: Prebiotics are effective modulators of gut health, driving clinical benefits through selective microbial fermentation and SCFA production. The documented heterogeneity and variability highlight the need for future research to focus on personalized nutritional strategies. Key priorities include standardizing intervention protocols, elucidating dose\u2013response relationships, integrating multi-omics data to link taxonomy to function, and exploring novel applications such as synbiotic formulations and gut\u2013brain axis modulation.<\/jats:p>","DOI":"10.3390\/nu18030372","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:52:38Z","timestamp":1769190758000},"page":"372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Prebiotics and Gut Health: Mechanisms, Clinical Evidence, and Future Directions"],"prefix":"10.3390","volume":"18","author":[{"given":"Cinara Regina A. V.","family":"Monteiro","sequence":"first","affiliation":[{"name":"Center of Biological and Health Sciences, Federal University of Maranh\u00e3o, Bacanga Campus, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"},{"name":"School of Physical Therapy, Florence University Center, S\u00e3o Lu\u00eds 65.020-490, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2656-8238","authenticated-orcid":false,"given":"Eduarda G.","family":"Bogea","sequence":"additional","affiliation":[{"name":"Center of Biological and Health Sciences, Federal University of Maranh\u00e3o, Bacanga Campus, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"},{"name":"School of Physical Therapy, Florence University Center, S\u00e3o Lu\u00eds 65.020-490, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-0662","authenticated-orcid":false,"given":"Carmem D. L.","family":"Campos","sequence":"additional","affiliation":[{"name":"Center of Biological and Health Sciences, Federal University of Maranh\u00e3o, Bacanga Campus, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Pereira-Filho","sequence":"additional","affiliation":[{"name":"Center of Biological and Health Sciences, Federal University of Maranh\u00e3o, Bacanga Campus, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane S. S.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Center of Biological and Health Sciences, Federal University of Maranh\u00e3o, Bacanga Campus, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 A. M.","family":"Vale","sequence":"additional","affiliation":[{"name":"Center of Biological and Health Sciences, Federal University of Maranh\u00e3o, Bacanga Campus, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6404-0103","authenticated-orcid":false,"given":"Ana Paula S.","family":"Azevedo-Santos","sequence":"additional","affiliation":[{"name":"Center of Biological and Health Sciences, Federal University of Maranh\u00e3o, Bacanga Campus, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2868-1314","authenticated-orcid":false,"given":"Val\u00e9rio","family":"Monteiro-Neto","sequence":"additional","affiliation":[{"name":"Center of Biological and Health Sciences, Federal University of Maranh\u00e3o, Bacanga Campus, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/gutjnl-2021-326789","article-title":"Gut microbiome and health: Mechanistic insights","volume":"71","author":"Tilg","year":"2022","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1084\/jem.20180448","article-title":"The gut microbiome: Relationships with disease and opportunities for therapy","volume":"216","author":"Durack","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1177\/1756283X13482996","article-title":"Role of the gut microbiota in health and chronic gastrointestinal disease: Understanding a hidden metabolic organ","volume":"6","author":"Guinane","year":"2013","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Breyner, N.M., Michon, C., de Sousa, C.S., Vilas Boas, P.B., Chain, F., Azevedo, V.A., Langella, P., and Chatel, J.M. (2017). Microbial Anti-Inflammatory Molecule (MAM) from Faecalibacterium prausnitzii Shows a Protective Effect on DNBS and DSS-Induced Colitis Model in Mice through Inhibition of NF-kappaB Pathway. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00114"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.jaci.2016.03.041","article-title":"Early-life gut microbiome composition and milk allergy resolution","volume":"138","author":"Bunyavanich","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Agusti, A., Garcia-Pardo, M.P., Lopez-Almela, I., Campillo, I., Maes, M., Romani-Perez, M., and Sanz, Y. (2018). Interplay Between the Gut-Brain Axis, Obesity and Cognitive Function. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00155"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12974-019-1434-3","article-title":"Impact of microbiota on central nervous system and neurological diseases: The gut-brain axis","volume":"16","author":"Ma","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41564-017-0089-z","article-title":"Dynamics of metatranscription in the inflammatory bowel disease gut microbiome","volume":"3","author":"Schirmer","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3177\/jnsv.64.357","article-title":"The Impact of Fructo-Oligosaccharides on Gut Permeability and Inflammatory Responses in the Cecal Mucosa Quite Differs between Rats Fed Semi-Purified and Non-Purified Diets","volume":"64","author":"Genda","year":"2018","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41575-019-0173-3","article-title":"Probiotics and prebiotics in intestinal health and disease: From biology to the clinic","volume":"16","author":"Sanders","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114769","DOI":"10.1016\/j.biopha.2023.114769","article-title":"Lactulose regulates gut microbiota dysbiosis and promotes short-chain fatty acids production in acute pancreatitis patients with intestinal dysfunction","volume":"163","author":"Wang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Davani-Davari, D., Negahdaripour, M., Karimzadeh, I., Seifan, M., Mohkam, M., Masoumi, S.J., Berenjian, A., and Ghasemi, Y. (2019). Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods, 8.","DOI":"10.3390\/foods8030092"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrgastro.2017.75","article-title":"Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics","volume":"14","author":"Gibson","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"306S","DOI":"10.3945\/an.113.005124","article-title":"Bioactive foods and ingredients for health","volume":"5","author":"Weaver","year":"2014","journal-title":"Adv. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7577","DOI":"10.1007\/s13197-015-1921-1","article-title":"Probiotics, prebiotics and synbiotics\u2014A review","volume":"52","author":"Pandey","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.jff.2013.08.009","article-title":"Prebiotics as functional foods: A review","volume":"5","author":"Ismail","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_17","unstructured":"Pandey, A., H\u00f6fer, R., Taherzadeh, M., Nampoothiri, K.M., and Larroche, C. (2015). Production and Extraction of Polysaccharides and Oligosaccharides and Their Use as New Food Additives. Industrial Biorefineries & White Biotechnology, Elsevier."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ejbt.2014.07.004","article-title":"Plant prebiotics and human health: Biotechnology to breed prebiotic-rich nutritious food crops","volume":"17","author":"Dwivedi","year":"2014","journal-title":"Electron. J. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.carres.2016.11.007","article-title":"Infant food applications of complex carbohydrates: Structure, synthesis, and function","volume":"437","author":"Ackerman","year":"2017","journal-title":"Carbohydr. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fernandes, P. (2025). Fructooligosaccharides (FOSs): A Condensed Overview. Compounds, 5.","DOI":"10.3390\/compounds5020008"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/ijfs.15379","article-title":"Structural characterisation, biological activities and pharmacological potential of glycosaminoglycans and oligosaccharides: A review","volume":"57","author":"Sharma","year":"2022","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_22","first-page":"435","article-title":"Fructooligosaccharides from Inulin as Prebiotics","volume":"48","author":"Singh","year":"2010","journal-title":"Food Technol. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tungland, B. (2018). Overview of prebiotics: Membership, physiological effects and their health attributes. Hum. Microbiota Health Dis., 289\u2013348.","DOI":"10.1016\/B978-0-12-814649-1.00007-7"},{"key":"ref_24","first-page":"S45","article-title":"Bifidogenic and Butyrogenic Effects of Inulin-Type Fructans and Arabinoxylans","volume":"63","author":"Selak","year":"2016","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e02893-17","DOI":"10.1128\/AEM.02893-17","article-title":"Complementary Mechanisms for Degradation of Inulin-Type Fructans and Arabinoxylan Oligosaccharides among Bifidobacterial Strains Suggest Bacterial Cooperation","volume":"84","author":"Riviere","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Samtiya, M., Aluko, R.E., Dhewa, T., and Moreno-Rojas, J.M. (2021). Potential Health Benefits of Plant Food-Derived Bioactive Components: An Overview. Foods, 10.","DOI":"10.3390\/foods10040839"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Villaluenga, C., and Fr\u00edas, J. (2014). Production and Bioactivity of Oligosaccharides in Plant Foods. Food Oligosaccharides, John Wiley & Sons.","DOI":"10.1002\/9781118817360.ch3"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.3390\/md13085358","article-title":"Proteins and Carbohydrates from Red Seaweeds: Evidence for Beneficial Effects on Gut Function and Microbiota","volume":"13","author":"Cian","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Guo, Y., Bian, X., Liu, J., Zhu, M., Li, L., Yao, T., Tang, C., Ravichandran, V., Liao, P., and Papadimitriou, K. (2020). Dietary Components, Microbial Metabolites and Human Health: Reading between the Lines. Foods, 9.","DOI":"10.3390\/foods9081045"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lopez-Santamarina, A., Sinisterra-Loaiza, L., Mondragon-Portocarrero, A., Ortiz-Viedma, J., Cardelle-Cobas, A., Abuin, C.M.F., and Cepeda, A. (2023). Potential prebiotic effect of two Atlantic whole brown seaweeds, Saccharina japonica and Undaria pinnatifida, using in vitro simulation of distal colonic fermentation. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1170392"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ijbiomac.2020.02.168","article-title":"Current trends in marine algae polysaccharides: The digestive tract, microbial catabolism, and prebiotic potential","volume":"151","author":"Zheng","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s11274-020-02961-9","article-title":"The prebiotics (Fructo-oligosaccharides and Xylo-oligosaccharides) modulate the probiotic properties of Lactiplantibacillus and Levilactobacillus strains isolated from traditional fermented olive","volume":"36","author":"Abouloifa","year":"2020","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jnutbio.2013.05.001","article-title":"Benefits of polyphenols on gut microbiota and implications in human health","volume":"24","author":"Cardona","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Guarino, M.P., Altomare, A., Emerenziani, S., Di Rosa, C., Ribolsi, M., Balestrieri, P., Iovino, P., Rocchi, G., and Cicala, M. (2020). Mechanisms of Action of Prebiotics and Their Effects on Gastro-Intestinal Disorders in Adults. Nutrients, 12.","DOI":"10.3390\/nu12041037"},{"key":"ref_35","unstructured":"Floch, M.H., Ringel, Y., and Allan Walker, W. (2017). Prebiotics: Inulin and Other Oligosaccharides. The Microbiota in Gastrointestinal Pathophysiology, Academic Press."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1080\/09637486.2017.1404970","article-title":"In vitro fermentation of gum acacia\u2014Impact on the faecal microbiota","volume":"69","author":"Alarifi","year":"2018","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.3168\/jds.2018-15410","article-title":"Effects of oligosaccharides on the fermentation properties of Lactobacillus plantarum","volume":"102","author":"Cao","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/jam.12105","article-title":"Selective carbohydrate utilization by lactobacilli and bifidobacteria","volume":"114","author":"Watson","year":"2013","journal-title":"J. Appl. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.carbpol.2019.03.050","article-title":"Chemical characterization of fructooligosaccharides, inulin and structurally diverse polysaccharides from chamomile tea","volume":"214","author":"Chaves","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_40","first-page":"315","article-title":"Inulin-type prebiotics\u2014A review: Part 1","volume":"13","author":"Kelly","year":"2008","journal-title":"Altern. Med. Rev."},{"key":"ref_41","unstructured":"Brandelli, A. (2022). Prebiotics and synbiotics. Probiotics, Academic Press."},{"key":"ref_42","unstructured":"Caballero, B. (2023). Probiotics and prebiotics. Encyclopedia of Human Nutrition, Academic Press."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.tifs.2021.02.047","article-title":"Current status of xylooligosaccharides: Production, characterization, health benefits and food application","volume":"111","author":"Palaniappan","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1093\/glycob\/cwt007","article-title":"Annotation and structural elucidation of bovine milk oligosaccharides and determination of novel fucosylated structures","volume":"23","author":"Aldredge","year":"2013","journal-title":"Glycobiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1818S","DOI":"10.1093\/jn\/138.9.1818S","article-title":"Structural and functional aspects of prebiotics used in infant nutrition","volume":"138","author":"Boehm","year":"2008","journal-title":"J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ganzle, M.G., and Follador, R. (2012). Metabolism of oligosaccharides and starch in lactobacilli: A review. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00340"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.3945\/jn.108.094367","article-title":"Structurally different wheat-derived arabinoxylooligosaccharides have different prebiotic and fermentation properties in rats","volume":"138","author":"Swennen","year":"2008","journal-title":"J. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Rios-Covian, D., Ruas-Madiedo, P., Margolles, A., Gueimonde, M., de Los Reyes-Gavilan, C.G., and Salazar, N. (2016). Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00185"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mansuy-Aubert, V., and Ravussin, Y. (2023). Short chain fatty acids: The messengers from down below. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1197759"},{"key":"ref_50","first-page":"381","article-title":"Short chain fatty acids as epigenetic and metabolic regulators of neurocognitive health and disease","volume":"Volume 14","author":"Ferguson","year":"2019","journal-title":"Nutritional Epigenomics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"230014","DOI":"10.1098\/rsob.230014","article-title":"Short chain fatty acids: Key regulators of the local and systemic immune response in inflammatory diseases and infections","volume":"13","author":"Ney","year":"2023","journal-title":"Open Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1017\/S0029665114001463","article-title":"Links between diet, gut microbiota composition and gut metabolism","volume":"74","author":"Flint","year":"2015","journal-title":"Proc. Nutr. Soc."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Schwiertz, A. (2016). Microbiota of the Human Body\u2014Implications in Health and Disease, Springer.","DOI":"10.1007\/978-3-319-31248-4"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cell.2013.12.016","article-title":"Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits","volume":"156","author":"Goncalves","year":"2014","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1080\/19490976.2017.1290756","article-title":"Dietary fiber and prebiotics and the gastrointestinal microbiota","volume":"8","author":"Holscher","year":"2017","journal-title":"Gut Microbes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nature18309","article-title":"Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome","volume":"534","author":"Perry","year":"2016","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1038\/ijo.2015.84","article-title":"The role of short chain fatty acids in appetite regulation and energy homeostasis","volume":"39","author":"Byrne","year":"2015","journal-title":"Int. J. Obes."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41538-023-00195-1","article-title":"Evaluating the prebiotic effect of oligosaccharides on gut microbiome wellness using in vitro fecal fermentation","volume":"7","author":"Lee","year":"2023","journal-title":"npj Sci. Food"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1039\/C4FO01082E","article-title":"In vitro fermentation of fructooligosaccharides with human gut bacteria","volume":"6","author":"Mao","year":"2015","journal-title":"Food Funct."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"114009","DOI":"10.1016\/j.fct.2023.114009","article-title":"Fermentation patterns of prebiotics fructooligosaccharides-SCFA esters inoculated with fecal microbiota from ulcerative colitis patients","volume":"180","author":"Chen","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1039\/D3FO04855A","article-title":"Dynamic response of different types of gut microbiota to fructooligosaccharides and inulin","volume":"15","author":"Yin","year":"2024","journal-title":"Food Funct."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"21796","DOI":"10.3402\/fnr.v58.21796","article-title":"Calcium and vitamin D supplementation: State of the art for daily practice","volume":"58","author":"Brouwers","year":"2014","journal-title":"Food Nutr. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00223-017-0339-3","article-title":"Prebiotics, Bone and Mineral Metabolism","volume":"102","author":"Whisner","year":"2018","journal-title":"Calcif. Tissue Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.phanu.2016.10.003","article-title":"Production of impure prebiotic galacto-oligosaccharides and their effect on calcium, magnesium, iron and zinc absorption in Sprague-Dawley rats","volume":"4","author":"Maawia","year":"2016","journal-title":"PharmaNutrition"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1039\/C6FO01833E","article-title":"Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humans","volume":"8","author":"Weinborn","year":"2017","journal-title":"Food Funct."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s13668-018-0248-8","article-title":"Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health","volume":"7","author":"Chambers","year":"2018","journal-title":"Curr. Nutr. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/cmi.2017.57","article-title":"Microbiota or short-chain fatty acids: Which regulates diabetes?","volume":"15","author":"Kim","year":"2018","journal-title":"Cell Mol. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.clnu.2014.10.004","article-title":"A systematic review and meta-analysis of the prebiotics and synbiotics effects on glycaemia, insulin concentrations and lipid parameters in adult patients with overweight or obesity","volume":"34","author":"Beserra","year":"2015","journal-title":"Clin. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1177\/0148607113510182","article-title":"Motilin and gastrin secretion and lipid profile in preterm neonates following prebiotics supplementation: A double-blind randomized controlled study","volume":"39","author":"Dasopoulou","year":"2015","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Simon, E., Calinoiu, L.F., Mitrea, L., and Vodnar, D.C. (2021). Probiotics, Prebiotics, and Synbiotics: Implications and Beneficial Effects against Irritable Bowel Syndrome. Nutrients, 13.","DOI":"10.3390\/nu13062112"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41575-019-0157-3","article-title":"The role of short-chain fatty acids in microbiota-gut-brain communication","volume":"16","author":"Dalile","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The Microbiota-Gut-Brain Axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.yclnex.2016.01.003","article-title":"Food for thought: The role of nutrition in the microbiota-gut\u2013brain axis","volume":"6","author":"Oriach","year":"2016","journal-title":"Clin. Nutr. Exp."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s11481-023-10069-8","article-title":"Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Improve Neuroinflammation and Cognition By Up-regulating IRS\/PI3K\/AKT Signaling Pathway in Diet-induced Obese Mice","volume":"18","author":"Mendonca","year":"2023","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Johnson, A.J., Zheng, J.J., Kang, J.W., Saboe, A., Knights, D., and Zivkovic, A.M. (2020). A Guide to Diet-Microbiome Study Design. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.00079"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1136\/gutjnl-2016-313271","article-title":"Prebiotic inulin-type fructans induce specific changes in the human gut microbiota","volume":"66","author":"Vandeputte","year":"2017","journal-title":"Gut"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Voreades, N., Kozil, A., and Weir, T.L. (2014). Diet and the development of the human intestinal microbiome. Front. Microbiol., 5.","DOI":"10.3389\/fmicb.2014.00494"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3945\/jn.112.166132","article-title":"A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults","volume":"143","author":"Vulevic","year":"2013","journal-title":"J. Nutr."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Wilson, B., Eyice, O., Koumoutsos, I., Lomer, M.C., Irving, P.M., Lindsay, J.O., and Whelan, K. (2021). Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms. Nutrients, 13.","DOI":"10.3390\/nu13103598"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.nutres.2014.08.004","article-title":"Long-term intake of a high prebiotic fiber diet but not high protein reduces metabolic risk after a high fat challenge and uniquely alters gut microbiota and hepatic gene expression","volume":"34","author":"Saha","year":"2014","journal-title":"Nutr. Res."},{"key":"ref_83","first-page":"541","article-title":"Effect of inulin on the human gut microbiota: Stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii","volume":"101","author":"Slezak","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1136\/gutjnl-2015-309618","article-title":"Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates","volume":"65","author":"Vandeputte","year":"2016","journal-title":"Gut"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1126\/science.1208344","article-title":"Linking long-term dietary patterns with gut microbial enterotypes","volume":"334","author":"Wu","year":"2011","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.copbio.2014.10.006","article-title":"Novel opportunities for next-generation probiotics targeting metabolic syndrome","volume":"32","author":"Cani","year":"2015","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2014.09.053","article-title":"Human genetics shape the gut microbiome","volume":"159","author":"Goodrich","year":"2014","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nature16504","article-title":"Diet-induced extinctions in the gut microbiota compound over generations","volume":"529","author":"Sonnenburg","year":"2016","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1146\/annurev-food-022510-133739","article-title":"Synbiotics in health and disease","volume":"2","author":"Kolida","year":"2011","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Drabi\u0144ska, N., Jarocka-Cyrta, E., Markiewicz, L.H., and Krupa-Kozak, U. (2018). The Effect of Oligofructose-Enriched Inulin on Faecal Bacterial Counts and Microbiota-Associated Characteristics in Celiac Disease Children Following a Gluten-Free Diet: Results of a Randomized, Placebo-Controlled Trial. Nutrients, 10.","DOI":"10.3390\/nu10020201"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1053\/j.gastro.2017.05.055","article-title":"Prebiotics Reduce Body Fat and Alter Intestinal Microbiota in Children Who Are Overweight or with Obesity","volume":"153","author":"Nicolucci","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4427","DOI":"10.1210\/jc.2019-00481","article-title":"Effect of Prebiotic on Microbiota, Intestinal Permeability, and Glycemic Control in Children with Type 1 Diabetes","volume":"104","author":"Ho","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3920\/BM2018.0116","article-title":"Prebiotic supplementation over a cold season and during antibiotic treatment specifically modulates the gut microbiota composition of 3-6 year-old children","volume":"10","author":"Soldi","year":"2019","journal-title":"Benef. Microbes"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Souza, D.D.S., Tahan, S., Weber, T.K., Araujo-Filho, H.B., and de Morais, M.B. (2018). Randomized, Double-Blind, Placebo-Controlled Parallel Clinical Trial Assessing the Effect of Fructooligosaccharides in Infants with Constipation. Nutrients, 10.","DOI":"10.3390\/nu10111602"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5009","DOI":"10.1016\/j.clnu.2021.05.033","article-title":"Prebiotic fructans have greater impact on luminal microbiology and CD3+ T cells in healthy siblings than patients with Crohn\u2019s disease: A pilot study investigating the potential for primary prevention of inflammatory bowel disease","volume":"40","author":"Hedin","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1080\/19490976.2018.1526583","article-title":"Inulin-type fructans improve active ulcerative colitis associated with microbiota changes and increased short-chain fatty acids levels","volume":"10","author":"Valcheva","year":"2019","journal-title":"Gut Microbes"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ejcn.2015.192","article-title":"Effect of inulin and fructo-oligosaccharide on the prevention of acute radiation enteritis in patients with gynecological cancer and impact on quality-of-life: A randomized, double-blind, placebo-controlled trial","volume":"70","author":"Velasco","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Schoemaker, M.H., Hageman, J.H.J., ten Haaf, D., Hartog, A., Scholtens, P.A.M.J., Boekhorst, J., Nauta, A., and Bos, R. (2022). Prebiotic Galacto-Oligosaccharides Impact Stool Frequency and Fecal Microbiota in Self-Reported Constipated Adults: A Randomized Clinical Trial. Nutrients, 14.","DOI":"10.3390\/nu14020309"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1093\/ajcn\/nqaa074","article-title":"Effect of chicory inulin-type fructan-containing snack bars on the human gut microbiota in low dietary fiber consumers in a randomized crossover trial","volume":"111","author":"Reimer","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1111\/apt.17387","article-title":"Efficacy of 1-kestose supplementation in patients with mild to moderate ulcerative colitis: A randomised, double-blind, placebo-controlled pilot study","volume":"57","author":"Ikegami","year":"2023","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1007\/s00394-020-02282-5","article-title":"Prebiotic effect of inulin-type fructans on faecal microbiota and short-chain fatty acids in type 2 diabetes: A randomised controlled trial","volume":"59","author":"Birkeland","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1053\/j.jrn.2020.10.003","article-title":"Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study","volume":"31","author":"Biruete","year":"2021","journal-title":"J. Ren. Nutr."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2078520","DOI":"10.1155\/2022\/2078520","article-title":"Overall Structural Alteration of Gut Microbiota and Relationships with Risk Factors in Patients with Metabolic Syndrome Treated with Inulin Alone and with Other Agents: An Open-Label Pilot Study","volume":"2022","author":"Tian","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1017\/S0007114516000908","article-title":"beta2-1 Fructan supplementation alters host immune responses in a manner consistent with increased exposure to microbial components: Results from a double-blinded, randomised, cross-over study in healthy adults","volume":"115","author":"Clarke","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1017\/S0007114515001889","article-title":"Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons","volume":"114","author":"Vulevic","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e2000390","DOI":"10.1002\/mnfr.202000390","article-title":"Flexibility of Gut Microbiota in Ageing Individuals during Dietary Fiber Long-Chain Inulin Intake","volume":"65","author":"Kiewiet","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.1038\/s41598-019-41837-3","article-title":"A prospective randomized, double-blind, placebo-controlled, dose-response relationship study to investigate efficacy of fructo-oligosaccharides (FOS) on human gut microflora","volume":"9","author":"Tandon","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s12519-019-00315-6","article-title":"Intestinal microbiome analysis demonstrates azithromycin post-treatment effects improve when combined with lactulose","volume":"16","author":"Nikolaou","year":"2020","journal-title":"World J. Pediatr."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1159\/000322977","article-title":"Beneficial effects of probiotic bifidobacterium and galacto-oligosaccharide in patients with ulcerative colitis: A randomized controlled study","volume":"84","author":"Ishikawa","year":"2011","journal-title":"Digestion"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Neumer, F., Urraca, O., Alonso, J., Palencia, J., Varea, V., Theis, S., Rodriguez-Palmero, M., Moreno-Munoz, J.A., Guarner, F., and Veereman, G. (2021). Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula-A Randomized Controlled Trial. Nutrients, 13.","DOI":"10.3390\/nu13041276"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"53829","DOI":"10.18632\/oncotarget.17754","article-title":"Microbiota-gut-brain axis and the central nervous system","volume":"8","author":"Zhu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41575-020-0344-2","article-title":"The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics","volume":"17","author":"Swanson","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_113","first-page":"E367","article-title":"Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals","volume":"114","author":"Ritter","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41387-025-00408-4","article-title":"The promising effects of a multi-species synbiotic preparation on metabolic profile in elderly patients with type 2 diabetes and high cardiovascular risk: A randomized, triple-blind, placebo-controlled trial","volume":"16","author":"Dolatkhah","year":"2025","journal-title":"Nutr. Diabetes"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6026","DOI":"10.3390\/ijms13056026","article-title":"Beta-glucans improve growth, viability and colonization of probiotic microorganisms","volume":"13","author":"Russo","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e16618","DOI":"10.1097\/MD.0000000000016618","article-title":"A meta-analysis of the effects of probiotics and synbiotics in children with acute diarrhea","volume":"98","author":"Yang","year":"2019","journal-title":"Medicine"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/3\/372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:59:16Z","timestamp":1769191156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/3\/372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":116,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["nu18030372"],"URL":"https:\/\/doi.org\/10.3390\/nu18030372","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}