{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:26:49Z","timestamp":1792016809899,"version":"4.4.0"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK34987"],"award-info":[{"award-number":["P30DK34987"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Lactose intolerance, characterized by a decrease in host lactase expression, affects approximately 75% of the world population. Galacto-oligosaccharides (GOS) are prebiotics that have been shown to alleviate symptoms of lactose intolerance and to modulate the intestinal microbiota, promoting the growth of beneficial microorganisms. We hypothesized that mechanisms of GOS utilization by intestinal bacteria are variable, impacting efficacy and response, with differences occurring at the strain level. This study aimed to determine the mechanisms by which human-derived Lactobacillus rhamnosus strains metabolize GOS. Genomic comparisons between strains revealed differences in carbohydrate utilization components, including transporters, enzymes for degradation, and transcriptional regulation, despite a high overall sequence identity (&gt;95%) between strains. Physiological and transcriptomics analyses showed distinct differences in carbohydrate metabolism profiles and GOS utilization between strains. A putative operon responsible for GOS utilization was identified and characterized by genetic disruption of the 6-phospho-\u03b2-galactosidase, which had a critical role in GOS utilization. Our findings highlight the importance of strain-specific bacterial metabolism in the selection of probiotics and synbiotics to alleviate symptoms of gastrointestinal disorders including lactose intolerance.<\/jats:p>","DOI":"10.3390\/nu10101517","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T11:07:51Z","timestamp":1539688071000},"page":"1517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Prebiotics for Lactose Intolerance: Variability in Galacto-Oligosaccharide Utilization by Intestinal Lactobacillus rhamnosus"],"prefix":"10.3390","volume":"10","author":[{"given":"Jason W.","family":"Arnold","sequence":"first","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, and UNC Microbiome Core, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua B.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, and UNC Microbiome Core, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery","family":"Roach","sequence":"additional","affiliation":[{"name":"Research Computing, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M.","family":"Bruno-Barcena","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-1289","authenticated-orcid":false,"given":"M. Andrea","family":"Azcarate-Peril","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, and UNC Microbiome Core, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8020","DOI":"10.3390\/nu7095380","article-title":"Lactose intolerance in adults: Biological mechanism and dietary management","volume":"7","author":"Deng","year":"2015","journal-title":"Nutrients"},{"key":"ref_2","unstructured":"Oak, S.J., and Jha, R. (2018). The effects of probiotics in lactose intolerance: A systematic review. Crit. Rev. Food Sci. Nutr., 1\u20139."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/1475-2891-12-160","article-title":"Improving lactose digestion and symptoms of lactose intolerance with a novel galacto-oligosaccharide (RP-G28): A randomized, double-blind clinical trial","volume":"12","author":"Savaiano","year":"2013","journal-title":"Nutr. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S-893","DOI":"10.1016\/S0016-5085(13)63323-5","article-title":"Microbiome alterations of lactose intolerant individuals in response to dietary intervention with galacto-oligosaccharides may help negate symptoms of lactose intolerance","volume":"144","author":"Savaiano","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Davis, L.M., Martinez, I., Walter, J., Goin, C., and Hutkins, R.W. (2011). Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025200"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/j.1541-4337.2010.00119.x","article-title":"Galacto-oligosaccharides: Production, properties, applications, and significance as prebiotics","volume":"9","author":"Torres","year":"2010","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_8","unstructured":"Chey, W.D., Sandborn, W.J., Ritter, A.J., Foyt, H., Azcarate-Peril, M.A., and Savaiano, D.A. (2018). Multiple clinical outcomes improve in lactose intolerance patients after treatment with novel galacto-oligosaccharide, RP-G28, Unpublished work."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ijfoodmicro.2011.05.026","article-title":"Galactooligosaccharides derived from lactose and lactulose: Influence of structure on Lactobacillus, Streptococcus and Bifidobacterium growth","volume":"149","author":"Corzo","year":"2011","journal-title":"Int. J. Food Microbiol."},{"key":"ref_10","first-page":"420","article-title":"Effect of lactose on gut microbiota and metabolome of infants with cow\u2019s milk allergy","volume":"23","author":"Francavilla","year":"2012","journal-title":"Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1021\/bi500656m","article-title":"L-galactose metabolism in Bacteroides vulgatus from the human gut microbiota","volume":"53","author":"Hobbs","year":"2014","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Do, M.H., Lee, E., Oh, M.J., Kim, Y., and Park, H.Y. (2018). High-glucose or -fructose diet cause changes of the gut microbiota and metabolic disorders in mice without body weight change. Nutrients, 10.","DOI":"10.3390\/nu10060761"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1128\/AEM.06192-11","article-title":"Functional analysis of Lactobacillus rhamnosus GG pili in relation to adhesion and immunomodulatory interactions with intestinal epithelial cells","volume":"78","author":"Lebeer","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1365-2249.2007.03522.x","article-title":"Differential immunomodulatory properties of Bifidobacterium longum strains: Relevance to probiotic selection and clinical applications","volume":"150","author":"Medina","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mib.2013.12.002","article-title":"Emerging insights on intestinal dysbiosis during bacterial infections","volume":"17","author":"Pham","year":"2014","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1128\/aem.63.2.513-518.1997","article-title":"Antagonistic activity exerted in vitro and in vivo by Lactobacillus casei (strain GG) against Salmonella typhimurium c5 infection","volume":"63","author":"Hudault","year":"1997","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"391","DOI":"10.2174\/138920211797248619","article-title":"Microbial metabolomics","volume":"12","author":"Tang","year":"2011","journal-title":"Curr. Genom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1053\/j.gastro.2014.03.001","article-title":"The intestinal metabolome: An intersection between microbiota and host","volume":"146","author":"Ursell","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3389\/fimmu.2015.00467","article-title":"Nutritional modulation of gene expression: Might this be of benefit to individuals with crohn\u2019s disease?","volume":"6","author":"Ferguson","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1016\/j.febslet.2014.03.035","article-title":"Beneficial modulation of the gut microbiota","volume":"588","author":"Walsh","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2658","DOI":"10.1097\/MD.0000000000002658","article-title":"Clinical uses of probiotics","volume":"95","author":"Islam","year":"2016","journal-title":"Medicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1128\/CMR.16.4.658-672.2003","article-title":"Potential uses of probiotics in clinical practice","volume":"16","author":"Reid","year":"2003","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_23","first-page":"99","article-title":"Prebiotics: Concept, properties and beneficial effects","volume":"31","author":"Corzo","year":"2015","journal-title":"Nutr. Hosp."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/00004836-200308000-00004","article-title":"New scientific paradigms for probiotics and prebiotics","volume":"37","author":"Reid","year":"2003","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1128\/AEM.00336-14","article-title":"Altered transcription of murine genes induced in the small bowel by administration of probiotic strain Lactobacillus rhamnosus HN001","volume":"80","author":"Tannock","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.anaerobe.2012.05.004","article-title":"In vitro evaluation of single- and multi-strain probiotics: Inter-species inhibition between probiotic strains, and inhibition of pathogens","volume":"18","author":"Chapman","year":"2012","journal-title":"Anaerobe"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1111\/j.1365-2672.2006.02857.x","article-title":"Antagonistic activity of probiotic lactobacilli and bifidobacteria against entero- and uropathogens","volume":"100","author":"Hutt","year":"2006","journal-title":"J. Appl. Microbiol."},{"key":"ref_28","first-page":"1","article-title":"Probiotics, prebiotics, and synbiotics","volume":"111","author":"Schrezenmeir","year":"2008","journal-title":"Adv. Biochem. Eng. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1128\/MMBR.00017-08","article-title":"Genes and molecules of lactobacilli supporting probiotic action","volume":"72","author":"Lebeer","year":"2008","journal-title":"Microbiol. Mol. Boil. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Papadimitriou, K., Zoumpopoulou, G., Folign\u00e9, B., Alexandraki, V., Kazou, M., Pot, B., and Tsakalidou, E. (2015). Discovering probiotic microorganisms: In vitro, in vivo, genetic and omics approaches. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00058"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.anaerobe.2013.04.005","article-title":"Tolerance of Bifidobacterium human isolates to bile, acid and oxygen","volume":"21","author":"Andriantsoanirina","year":"2013","journal-title":"Anaerobe"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1128\/MMBR.00076-15","article-title":"Stress physiology of lactic acid bacteria","volume":"80","author":"Papadimitriou","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3389\/fmicb.2018.00242","article-title":"Intra-species genomic and physiological variability impact stress resistance in strains of probiotic potential","volume":"9","author":"Arnold","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.3390\/nu9091021","article-title":"Effects of probiotics, prebiotics, and synbiotics on human health","volume":"9","author":"Markowiak","year":"2017","journal-title":"Nutrients"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13073-016-0304-1","article-title":"Strain-level dissection of the contribution of the gut microbiome to human metabolic disease","volume":"8","author":"Zhang","year":"2016","journal-title":"Genome Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.cell.2014.12.038","article-title":"Extensive strain-level copy-number variation across human gut microbiome species","volume":"160","author":"Greenblum","year":"2015","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17785","DOI":"10.1073\/pnas.1114152108","article-title":"Transcriptional and functional analysis of galactooligosaccharide uptake by lacS in Lactobacillus acidophilus","volume":"108","author":"Andersen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Arnold, J.W., Monteagudo-Mera, A., Altermann, E., Cadenas, M.B., Thompson, A.L., and Azcarate-Peril, M.A. (2017). Genome sequences of potential probiotic isolates from human infants. Genome Announc., 5.","DOI":"10.1128\/genomeA.00107-17"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Thompson, A.L., Monteagudo-Mera, A., Cadenas, M.B., Lampl, M.L., and Azcarate-Peril, M. (2015). Milk-and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome. Front. Cell. Infect. Microbiol., 5.","DOI":"10.3389\/fcimb.2015.00003"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1128\/AAC.31.8.1231","article-title":"Antimicrobial substance from a human Lactobacillus strain","volume":"31","author":"Silva","year":"1987","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17193","DOI":"10.1073\/pnas.0908876106","article-title":"Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein","volume":"106","author":"Kankainen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jff.2014.10.029","article-title":"Galacto-oligosaccharides and colorectal cancer: Feeding our intestinal probiome","volume":"12","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1128\/AEM.03491-12","article-title":"Heterologous expression of a bioactive \u03b2-hexosyltransferase, an enzyme producer of prebiotics, from Sporobolomyces singularis","volume":"79","author":"Dagher","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/femsle\/fnu033","article-title":"High efficiency electrotransformation of Lactobacillus casei","volume":"362","author":"Welker","year":"2015","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1365-2672.2005.02563.x","article-title":"Optimization of technical conditions for the transformation of lactobacillus acidophilus strains by electroporation","volume":"99","author":"Kim","year":"2005","journal-title":"J. Appl. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1021\/acs.jafc.7b00851","article-title":"Prebiotic galactooligosaccharide metabolism by probiotic lactobacilli and bifidobacteria","volume":"65","author":"Thongaram","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kumari, M., Swarnkar, M.K., Kumar, S., Singh, A.K., and Gupta, M. (2015). Complete genome sequence of potential probiotic Lactobacillus sp. Hfc8, isolated from human gut using PacBio SMRT sequencing. Genome Announc., 3.","DOI":"10.1128\/genomeA.01337-15"},{"key":"ref_48","first-page":"61","article-title":"Automatic annotation of microbial genomes and metagenomic sequences in metagenomics and its applications in agriculture","volume":"18","author":"Solovyev","year":"2011","journal-title":"Biomed. Environ. Stud."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1006\/jmbi.2001.5102","article-title":"Direct RNA motif definition and identification from multiple sequence alignments using secondary structure profiles","volume":"313","author":"Gautheret","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1128\/JB.181.1.225-230.1999","article-title":"Lactobacillus casei 64h contains a phosphoenolpyruvate-dependent phosphotransferase system for uptake of galactose, as confirmed by analysis of ptsh and different gal mutants","volume":"181","author":"Bettenbrock","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2323\/jgam.58.11","article-title":"Purification and characterization of two phospho-\u03b2-galactosidases, lacg1 and lacg2, from Lactobacillus gasseri ATCC33323(t)","volume":"58","author":"Honda","year":"2012","journal-title":"J. Gen. Appl. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s00253-002-1153-y","article-title":"Food-grade host\/vector expression system for Lactobacillus casei based on complementation of plasmid-associated phospho-\u03b2-galactosidase gene lacg","volume":"60","author":"Takala","year":"2003","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1271\/bbb.62.2318","article-title":"Molecular cloning and sequencing of two phospho-\u03b2-galactosidase I and II genes of Lactobacillus gasseri JCM1031 isolated from human intestine","volume":"62","author":"Saito","year":"1998","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7152","DOI":"10.1038\/s41598-018-25660-w","article-title":"The lactose operon from Lactobacillus casei is involved in the transport and metabolism of the human milk oligosaccharide core-2 n-acetyllactosamine","volume":"8","author":"Bidart","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1271\/bbb.60.708","article-title":"Coexistence of two kinds of 6-phospho-\u03b2-galactosidase in the cytosol of Lactobacillus gasseri JCM1031--purification and characterization of 6-phospho-\u03b2-galactosidase II","volume":"60","author":"Suzuki","year":"1996","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1271\/bbb.60.139","article-title":"Purification and characterization of 6-phospho-\u03b2-galactosidase from Lactobacillus gasseri JCM1031","volume":"60","author":"Suzuki","year":"1996","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.femsle.2005.03.044","article-title":"Marker-free chromosomal integration of the manganese superoxide dismutase gene (soda) from streptococcus thermophilus into Lactobacillus gasseri","volume":"246","author":"Klaenhammer","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.fm.2013.03.003","article-title":"Synbiotic impact of tagatose on viability of Lactobacillus rhamnosus strain GG mediated by the phosphotransferase system (PTS)","volume":"36","author":"Koh","year":"2013","journal-title":"Food Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3389\/fmicb.2012.00340","article-title":"Metabolism of oligosaccharides and starch in lactobacilli: A review","volume":"3","author":"Ganzle","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1128\/AEM.68.11.5464-5471.2002","article-title":"Characterization of the mela locus for \u03b1-galactosidase in Lactobacillus plantarum","volume":"68","author":"Silvestroni","year":"2002","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1128\/JB.00339-15","article-title":"A mannose family phosphotransferase system permease and associated enzymes are required for utilization of fructoselysine and glucoselysine in Salmonella enterica serovar typhimurium","volume":"197","author":"Miller","year":"2015","journal-title":"J. Bacteriol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.4319\/lo.1996.41.8.1591","article-title":"Modeling bacterial utilization of dissolved organic matter: Optimization replaces monod growth kinetics","volume":"41","author":"Vallino","year":"1996","journal-title":"Limnol. Oceanogr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1093\/gbe\/evw123","article-title":"The variable regions of Lactobacillus rhamnosus genomes reveal the dynamic evolution of metabolic and host-adaptation repertoires","volume":"8","author":"Ceapa","year":"2016","journal-title":"Genome Boil. Evol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/1574-6976.12058","article-title":"Conjugative and mobilizable genomic islands in bacteria: Evolution and diversity","volume":"38","author":"Bellanger","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_65","first-page":"157","article-title":"Molecular characterization of the plasmid-encoded lactose-pts of Lactobacillus casei","volume":"5","author":"Chassy","year":"1989","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1128\/JB.01629-12","article-title":"Maltose uptake by the novel abc transport system musEFGK2I causes increased expression of ptsG in Corynebacterium glutamicum","volume":"195","author":"Henrich","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s40168-018-0494-4","article-title":"Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics","volume":"6","author":"Krumbeck","year":"2018","journal-title":"Microbiome"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mitra, S., F\u00f6rster-Fromme, K., Damms-Machado, A., Scheurenbrand, T., Biskup, S., Huson, D.H., and Bischoff, S.C. (2013). Analysis of the intestinal microbiota using solid 16S rRNA gene sequencing and solid shotgun sequencing. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-S5-S16"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"D277","DOI":"10.1093\/nar\/gkh063","article-title":"The KEGG resource for deciphering the genome","volume":"32","author":"Kanehisa","year":"2004","journal-title":"Nucleic Acids Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/10\/1517\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:25:58Z","timestamp":1760196358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/10\/1517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,16]]},"references-count":69,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["nu10101517"],"URL":"https:\/\/doi.org\/10.3390\/nu10101517","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,16]]}}}