{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:37:01Z","timestamp":1747204621506,"version":"3.40.5"},"posted":{"date-parts":[[2023,3,13]]},"group-title":"In Review","reference-count":82,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,2,28]]},"abstract":"<title>Abstract<\/title>\n        <p>Purpose\n Patients with non-infectious complications have worse clinical outcomes in common variable immunodeficiency (CVID) than those with infections-only. Non-infectious complications are associated with gut microbiome aberrations, but there are no reductionist animal models that emulate CVID. Our aim in this study was to uncover potential microbiome roles in the development of non-infectious complications in CVID.\nMethods\n We examined fecal whole genome shotgun sequencing from patients CVID, and non-infectious complications, infections-only, and their household controls. We also performed Fecal Microbiota transplant from CVID patients to Germ-Free Mice.\nResults\n We found potentially pathogenic microbes <italic>Streptococcus parasanguinis<\/italic> and <italic>Erysipelatoclostridium ramosum<\/italic> were enriched in gut microbiomes of CVID patients with non-infectious complications. In contrast, <italic>Fusicatenibacter saccharivorans<\/italic> and <italic>Anaerostipes hadrus<\/italic>, known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of infections-only CVID patients. Fecal microbiota transplant from non-infectious complications, infections-only, and their household controls into germ-free mice revealed gut dysbiosis patterns in recipients from CVID patients with non-infectious complications, but not infections-only CVID, or household controls recipients.\nConclusion\n Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with non-infectious complications to Germ-Free mice recapitulates microbiome alterations observed in the donors.<\/p>","DOI":"10.21203\/rs.3.rs-2640584\/v1","type":"posted-content","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T14:53:48Z","timestamp":1678719228000},"source":"Crossref","is-referenced-by-count":7,"title":["Common Variable Immunodeficiency Patient Fecal Microbiota Transplant Recapitulates Gut Dysbiosis"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-1043","authenticated-orcid":false,"given":"Joud","family":"Hajjar","sequence":"first","affiliation":[{"name":"Baylor College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Voigt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Conner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alton","family":"Swennes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chadi","family":"Calarge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Mendonca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Yen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolan","family":"Walter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manish","family":"Butte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tor","family":"Savidge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farrah","family":"Kheradmand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Petrosino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fimmu.2020.00149","article-title":"Non-infectious Complications of Common Variable Immunodeficiency: Updated Clinical Spectrum, Sequelae, and Insights to Pathogenesis","volume":"11","author":"Ho HE","year":"2020","unstructured":"Ho HE, Cunningham-Rundles C. Non-infectious Complications of Common Variable Immunodeficiency: Updated Clinical Spectrum, Sequelae, and Insights to Pathogenesis. Front Immunol. 2020;11:149.","journal-title":"Front Immunol"},{"issue":"5","key":"ref2","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.jaci.2015.04.049","article-title":"Practice parameter for the diagnosis and management of primary immunodeficiency","volume":"136","author":"Bonilla FA","year":"2015","unstructured":"Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186\u2013205. e1-78.","journal-title":"J Allergy Clin Immunol"},{"issue":"7","key":"ref3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s40629-014-0030-4","article-title":"Immunodeficiency in adults a practical guide for the allergist","volume":"23","author":"Hausmann O","year":"2014","unstructured":"Hausmann O, Warnatz K. Immunodeficiency in adults a practical guide for the allergist. Allergo J Int. 2014;23(7):261\u20138.","journal-title":"Allergo J Int"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1182\/asheducation.V2012.1.301.3798316","article-title":"The many faces of common variable immunodeficiency","volume":"2012","author":"Cunningham-Rundles C","year":"2012","unstructured":"Cunningham-Rundles C. The many faces of common variable immunodeficiency. Hematol Am Soc Hematol Educ Program. 2012;2012:301\u20135.","journal-title":"Hematol Am Soc Hematol Educ Program"},{"issue":"6","key":"ref5","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/j.1365-2141.2009.07669.x","article-title":"Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions","volume":"145","author":"Chapel H","year":"2009","unstructured":"Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009;145(6):709\u201327.","journal-title":"Br J Haematol"},{"issue":"3","key":"ref6","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.jaci.2016.08.030","article-title":"Noninfectious complications in patients with pediatric-onset common variable immunodeficiency correlated with defects in somatic hypermutation but not in class-switch recombination","volume":"139","author":"Almejun MB","year":"2017","unstructured":"Almejun MB, Campos BC, Patino V, Galicchio M, Zelazko M, Oleastro M, et al. Noninfectious complications in patients with pediatric-onset common variable immunodeficiency correlated with defects in somatic hypermutation but not in class-switch recombination. J Allergy Clin Immunol. 2017;139(3):913\u201322.","journal-title":"J Allergy Clin Immunol"},{"issue":"5","key":"ref7","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.jaci.2016.12.978","article-title":"members of the CFPIDsg. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies","volume":"140","author":"Fischer A","year":"2017","unstructured":"Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N. members of the CFPIDsg. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017;140(5):1388\u201393e8.","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s11882-013-0350-3","article-title":"Autoimmunity in immunodeficiency","volume":"13","author":"Todoric K","year":"2013","unstructured":"Todoric K, Koontz JB, Mattox D, Tarrant TK. Autoimmunity in immunodeficiency. Curr Allergy Asthma Rep. 2013;13(4):361\u201370.","journal-title":"Curr Allergy Asthma Rep"},{"issue":"2","key":"ref9","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1182\/blood-2007-11-124545","article-title":"Common variable immunodeficiency disorders: division into distinct clinical phenotypes","volume":"112","author":"Chapel H","year":"2008","unstructured":"Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277\u201386.","journal-title":"Blood"},{"issue":"7","key":"ref10","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1182\/blood-2011-09-377945","article-title":"Morbidity and mortality in common variable immune deficiency over 4 decades","volume":"119","author":"Resnick ES","year":"2012","unstructured":"Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650\u20137.","journal-title":"Blood"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"605","DOI":"10.3389\/fimmu.2014.00605","article-title":"Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies","volume":"5","author":"Tabolli S","year":"2014","unstructured":"Tabolli S, Giannantoni P, Pulvirenti F, La Marra F, Granata G, Milito C, et al. Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies. Front Immunol. 2014;5:605.","journal-title":"Front Immunol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.3389\/fimmu.2017.01740","article-title":"Common Variable Immunodeficiency Non-Infectious Disease Endotypes Redefined Using Unbiased Network Clustering in Large Electronic Datasets","volume":"8","author":"Farmer JR","year":"2017","unstructured":"Farmer JR, Ong MS, Barmettler S, Yonker LM, Fuleihan R, Sullivan KE, et al. Common Variable Immunodeficiency Non-Infectious Disease Endotypes Redefined Using Unbiased Network Clustering in Large Electronic Datasets. Front Immunol. 2017;8:1740.","journal-title":"Front Immunol"},{"issue":"10","key":"ref13","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1084\/jem.20140039","article-title":"Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders","volume":"211","author":"Perreau M","year":"2014","unstructured":"Perreau M, Vigano S, Bellanger F, Pellaton C, Buss G, Comte D, et al. Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders. J Exp Med. 2014;211(10):2033\u201345.","journal-title":"J Exp Med"},{"year":"2016","author":"Jorgensen SF","key":"ref14","unstructured":"Jorgensen SF, Troseid M, Kummen M, Anmarkrud JA, Michelsen AE, Osnes LT et al. Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation.Mucosal Immunol. 2016."},{"year":"2021","author":"Ho H-E","key":"ref15","unstructured":"Ho H-E, Radigan L, Bongers G, El-Shamy A, Cunningham-Rundles C. Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency.JCI Insight. 2021;6(19)."},{"issue":"3","key":"ref16","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.it.2016.11.008","article-title":"Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences","volume":"38","author":"Berbers RM","year":"2017","unstructured":"Berbers RM, Nierkens S, van Laar JM, Bogaert D, Leavis HL. Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences. Trends Immunol. 2017;38(3):206\u201316.","journal-title":"Trends Immunol"},{"issue":"9","key":"ref17","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrmicro2848","article-title":"Microbial translocation in HIV infection: causes, consequences and treatment opportunities","volume":"10","author":"Sandler NG","year":"2012","unstructured":"Sandler NG, Douek DC. Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol. 2012;10(9):655\u201366.","journal-title":"Nat Rev Microbiol"},{"issue":"3\u20135","key":"ref18","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0171-2985(11)80353-0","article-title":"Response of man to endotoxin","volume":"187","author":"Martich GD","year":"1993","unstructured":"Martich GD, Boujoukos AJ, Suffredini AF. Response of man to endotoxin. Immunobiology. 1993;187(3\u20135):403\u201316.","journal-title":"Immunobiology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.3389\/fimmu.2019.01914","article-title":"Bacterial but Not Fungal Gut Microbiota Alterations Are Associated With Common Variable Immunodeficiency (CVID) Phenotype","volume":"10","author":"Fiedorova K","year":"2019","unstructured":"Fiedorova K, Radvansky M, Bosak J, Grombirikova H, Nemcova E, Kralickova P, et al. Bacterial but Not Fungal Gut Microbiota Alterations Are Associated With Common Variable Immunodeficiency (CVID) Phenotype. Front Immunol. 2019;10:1914.","journal-title":"Front Immunol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.3389\/fimmu.2020.01654","article-title":"Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea","volume":"11","author":"Schewick CM","year":"2020","unstructured":"van Schewick CM, N\u00f6ltner C, Abel S, Burns SO, Workman S, Symes A, et al. Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea. Front Immunol. 2020;11:1654.","journal-title":"Front Immunol"},{"issue":"1","key":"ref21","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s10875-018-0574-z","article-title":"Autoimmunity and Inflammation in CVID: a Possible Crosstalk between Immune Activation, Gut Microbiota, and Epigenetic Modifications","volume":"39","author":"J\u00f8rgensen SF","year":"2019","unstructured":"J\u00f8rgensen SF, Fevang B, Aukrust P. Autoimmunity and Inflammation in CVID: a Possible Crosstalk between Immune Activation, Gut Microbiota, and Epigenetic Modifications. J Clin Immunol. 2019;39(1):30\u20136.","journal-title":"J Clin Immunol"},{"issue":"6","key":"ref22","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1038\/mi.2016.18","article-title":"Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation","volume":"9","author":"Jorgensen SF","year":"2016","unstructured":"Jorgensen SF, Troseid M, Kummen M, Anmarkrud JA, Michelsen AE, Osnes LT, et al. Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Mucosal Immunol. 2016;9(6):1455\u201365.","journal-title":"Mucosal Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.clim.2018.09.008","article-title":"CVID enteropathy is characterized by exceeding low mucosal IgA levels and interferon-driven inflammation possibly related to the presence of a pathobiont","volume":"197","author":"Shulzhenko N","year":"2018","unstructured":"Shulzhenko N, Dong X, Vyshenska D, Greer RL, Gurung M, Vasquez-Perez S, et al. CVID enteropathy is characterized by exceeding low mucosal IgA levels and interferon-driven inflammation possibly related to the presence of a pathobiont. Clin Immunol. 2018;197:139\u201353.","journal-title":"Clin Immunol"},{"issue":"6371","key":"ref24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1126\/science.aan4236","article-title":"Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients","volume":"359","author":"Gopalakrishnan V","year":"2018","unstructured":"Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97\u2013103.","journal-title":"Science"},{"issue":"7346","key":"ref25","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/nature09944","article-title":"Enterotypes of the human gut microbiome","volume":"473","author":"Arumugam M","year":"2011","unstructured":"Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174\u201380.","journal-title":"Nature"},{"issue":"6","key":"ref26","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata N","year":"2011","unstructured":"Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60.","journal-title":"Genome Biol"},{"issue":"1","key":"ref27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13059-022-02610-4","article-title":"AGAMEMNON: an Accurate metaGenomics And MEtatranscriptoMics quaNtificatiON analysis suite","volume":"23","author":"Skoufos G","year":"2022","unstructured":"Skoufos G, Almodaresi F, Zakeri M, Paulson JN, Patro R, Hatzigeorgiou AG, et al. AGAMEMNON: an Accurate metaGenomics And MEtatranscriptoMics quaNtificatiON analysis suite. Genome Biol. 2022;23(1):39.","journal-title":"Genome Biol"},{"issue":"6","key":"ref28","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/s41592-021-01141-3","article-title":"Challenges in benchmarking metagenomic profilers","volume":"18","author":"Sun Z","year":"2021","unstructured":"Sun Z, Huang S, Zhang M, Zhu Q, Haiminen N, Carrieri AP, et al. Challenges in benchmarking metagenomic profilers. Nat Methods. 2021;18(6):618\u201326.","journal-title":"Nat Methods"},{"year":"2018","author":"Ajami NJ","key":"ref29","unstructured":"Ajami NJ, Cope JL, Wong MC, Petrosino JF, Chesnel L. Impact of Oral Fidaxomicin Administration on the Intestinal Microbiota and Susceptibility to Clostridium difficile Colonization in Mice.Antimicrob Agents Chemother. 2018;62(5)."},{"issue":"3","key":"ref30","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1136\/gutjnl-2020-322753","article-title":"Long-term instability of the intestinal microbiome is associated with metabolic liver disease, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function","volume":"70","author":"Frost F","year":"2021","unstructured":"Frost F, Kacprowski T, R\u00fchlemann M, Pietzner M, Bang C, Franke A, et al. Long-term instability of the intestinal microbiome is associated with metabolic liver disease, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function. Gut. 2021;70(3):522\u201330.","journal-title":"Gut"},{"issue":"8","key":"ref31","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1007\/s00125-021-05464-w","article-title":"Markers of metabolic health and gut microbiome diversity: findings from two population-based cohort studies","volume":"64","author":"Zouiouich S","year":"2021","unstructured":"Zouiouich S, Loftfield E, Huybrechts I, Viallon V, Louca P, Vogtmann E, et al. Markers of metabolic health and gut microbiome diversity: findings from two population-based cohort studies. Diabetologia. 2021;64(8):1749\u201359.","journal-title":"Diabetologia"},{"issue":"6","key":"ref32","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/s41591-019-0464-9","article-title":"Community ecology as a framework for human microbiome research","volume":"25","author":"Gilbert JA","year":"2019","unstructured":"Gilbert JA, Lynch SV. Community ecology as a framework for human microbiome research. Nat Med. 2019;25(6):884\u20139.","journal-title":"Nat Med"},{"key":"ref33","unstructured":"ATIMA. [Available from: https:\/\/atima.research.bcm.edu\/."},{"year":"2013","author":"Song SJ","key":"ref34","unstructured":"Song SJ, Lauber C, Costello EK, Lozupone CA, Humphrey G, Berg-Lyons D et al. Cohabiting family members share microbiota with one another and with their dogs.eLife. 2013;2."},{"issue":"7402","key":"ref35","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature11053","article-title":"Human gut microbiome viewed across age and geography","volume":"486","author":"Yatsunenko T","year":"2012","unstructured":"Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222\u20137.","journal-title":"Nature"},{"year":"2016","author":"Li H","key":"ref36","unstructured":"Li H, Li T, Beasley DE, Hed\u011bnec P, Xiao Z, Zhang S et al. Diet Diversity Is Associated with Beta but not Alpha Diversity of Pika Gut Microbiota.Frontiers in Microbiology. 2016;7."},{"issue":"5","key":"ref37","first-page":"359","article-title":"A Case of Pneumonia and Parapneumonic Effusion Caused by Streptococcus parasanguinis","volume":"71","author":"Park MR","year":"2011","unstructured":"Park MR, Park DI, Yoo SJ, Jung SY, Eun HS, Kim MJ, et al. A Case of Pneumonia and Parapneumonic Effusion Caused by Streptococcus parasanguinis. trd. 2011;71(5):359\u201362.","journal-title":"trd"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1590\/s1678-9946202163030","article-title":"Antimicrobial treatment of Erysipelatoclostridium ramosum invasive infections: a systematic review","volume":"63","author":"Milosavljevic MN","year":"2021","unstructured":"Milosavljevic MN, Kostic M, Milovanovic J, Zaric RZ, Stojadinovic M, Jankovic SM, et al. Antimicrobial treatment of Erysipelatoclostridium ramosum invasive infections: a systematic review. Rev Inst Med Trop Sao Paulo. 2021;63:e30.","journal-title":"Rev Inst Med Trop Sao Paulo"},{"issue":"12","key":"ref39","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1097\/MIB.0000000000000972","article-title":"A Single Species of Clostridium Subcluster XIVa Decreased in Ulcerative Colitis Patients","volume":"22","author":"Takeshita K","year":"2016","unstructured":"Takeshita K, Mizuno S, Mikami Y, Sujino T, Saigusa K, Matsuoka K, et al. A Single Species of Clostridium Subcluster XIVa Decreased in Ulcerative Colitis Patients. Inflamm Bowel Dis. 2016;22(12):2802\u201310.","journal-title":"Inflamm Bowel Dis"},{"issue":"6","key":"ref40","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1136\/gutjnl-2015-309184","article-title":"Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery","volume":"65","author":"Mondot S","year":"2016","unstructured":"Mondot S, Lepage P, Seksik P, Allez M, Treton X, Bouhnik Y, et al. Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery. Gut. 2016;65(6):954\u201362.","journal-title":"Gut"},{"key":"ref41"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"27572","DOI":"10.1038\/srep27572","article-title":"Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium","volume":"6","author":"Zhang Q","year":"2016","unstructured":"Zhang Q, Wu Y, Wang J, Wu G, Long W, Xue Z, et al. Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium. Sci Rep. 2016;6:27572.","journal-title":"Sci Rep"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41564-018-0337-x","article-title":"The neuroactive potential of the human gut microbiota in quality of life and depression","volume":"4","author":"Valles-Colomer M","year":"2019","unstructured":"Valles-Colomer M, Falony G, Darzi Y, Tigchelaar EF, Wang J, Tito RY, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019;4(4):623\u201332.","journal-title":"Nat Microbiol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.3389\/fimmu.2017.01166","article-title":"Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity","volume":"8","author":"Patterson AM","year":"2017","unstructured":"Patterson AM, Mulder IE, Travis AJ, Lan A, Cerf-Bensussan N, Gaboriau-Routhiau V, et al. Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity. Front Immunol. 2017;8:1166.","journal-title":"Front Immunol"},{"issue":"9\u201310","key":"ref45","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.molimm.2011.02.002","article-title":"Influence of gut microbiota on mouse B2 B cell ontogeny and function","volume":"48","author":"Hansson J","year":"2011","unstructured":"Hansson J, Bosco N, Favre L, Raymond F, Oliveira M, Metairon S, et al. Influence of gut microbiota on mouse B2 B cell ontogeny and function. Mol Immunol. 2011;48(9\u201310):1091\u2013101.","journal-title":"Mol Immunol"},{"issue":"11","key":"ref46","doi-asserted-by":"crossref","first-page":"e27662","DOI":"10.1371\/journal.pone.0027662","article-title":"The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice","volume":"6","author":"Lamouse-Smith ES","year":"2011","unstructured":"Lamouse-Smith ES, Tzeng A, Starnbach MN. The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice. PLoS ONE. 2011;6(11):e27662.","journal-title":"PLoS ONE"},{"issue":"2","key":"ref47","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0022-1759(98)00015-5","article-title":"The need for IgG2c specific antiserum when isotyping antibodies from C57BL\/6 and NOD mice","volume":"212","author":"Martin RM","year":"1998","unstructured":"Martin RM, Brady JL, Lew AM. The need for IgG2c specific antiserum when isotyping antibodies from C57BL\/6 and NOD mice. J Immunol Methods. 1998;212(2):187\u201392.","journal-title":"J Immunol Methods"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"107944","DOI":"10.1016\/j.exppara.2020.107944","article-title":"Measuring of IgG2c isotype instead of IgG2a in immunized C57BL\/6 mice with Plasmodium vivax TRAP as a subunit vaccine candidate in order to correct interpretation of Th1 versus Th2 immune response","volume":"216","author":"Nazeri S","year":"2020","unstructured":"Nazeri S, Zakeri S, Mehrizi AA, Sardari S, Djadid ND. Measuring of IgG2c isotype instead of IgG2a in immunized C57BL\/6 mice with Plasmodium vivax TRAP as a subunit vaccine candidate in order to correct interpretation of Th1 versus Th2 immune response. Exp Parasitol. 2020;216:107944.","journal-title":"Exp Parasitol"},{"issue":"1","key":"ref49","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1038\/s41598-018-21039-z","article-title":"Identification of T helper (Th)1- and Th2-associated antigens of Cryptococcus neoformans in a murine model of pulmonary infection","volume":"8","author":"Firacative C","year":"2018","unstructured":"Firacative C, Gressler AE, Schubert K, Schulze B, M\u00fcller U, Brombacher F, et al. Identification of T helper (Th)1- and Th2-associated antigens of Cryptococcus neoformans in a murine model of pulmonary infection. 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Single Sampling Versus Multiple Testing Strategy to Assess Gut Microbiota Composition: Does It Matter? Curr Microbiol. 2019;76(9):1081.","journal-title":"Curr Microbiol"},{"key":"ref62","unstructured":"Consortium Ti. Household paired design reduces variance and increases power in multi-city gut microbiome study in multiple sclerosis.Mult Scler. 2020:1352458520924594."},{"key":"ref63","doi-asserted-by":"crossref","first-page":"e00458","DOI":"10.7554\/eLife.00458","article-title":"Cohabiting family members share microbiota with one another and with their dogs","volume":"2","author":"Song SJ","year":"2013","unstructured":"Song SJ, Lauber C, Costello EK, Lozupone CA, Humphrey G, Berg-Lyons D, et al. Cohabiting family members share microbiota with one another and with their dogs. Elife. 2013;2:e00458.","journal-title":"Elife"},{"issue":"11","key":"ref64","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1128\/JCM.01563-10","article-title":"It's not easy being green: the viridans group streptococci, with a focus on pediatric clinical manifestations","volume":"48","author":"Doern CD","year":"2010","unstructured":"Doern CD, Burnham CA. It's not easy being green: the viridans group streptococci, with a focus on pediatric clinical manifestations. J Clin Microbiol. 2010;48(11):3829\u201335.","journal-title":"J Clin Microbiol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jdent.2016.02.007","article-title":"Antimicrobial effects of commensal oral species are regulated by environmental factors","volume":"47","author":"Herrero ER","year":"2016","unstructured":"Herrero ER, Slomka V, Bernaerts K, Boon N, Hernandez-Sanabria E, Passoni BB, et al. Antimicrobial effects of commensal oral species are regulated by environmental factors. J Dent. 2016;47:23\u201333.","journal-title":"J Dent"},{"issue":"8","key":"ref66","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/j.1469-0691.2007.01753.x","article-title":"Characteristics and regional variations of group D streptococcal endocarditis in France","volume":"13","author":"Giannitsioti E","year":"2007","unstructured":"Giannitsioti E, Chirouze C, Bouvet A, B\u00e9guinot I, Delahaye F, Mainardi JL, et al. Characteristics and regional variations of group D streptococcal endocarditis in France. Clin Microbiol Infect. 2007;13(8):770\u20136.","journal-title":"Clin Microbiol Infect"},{"issue":"1","key":"ref67","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13073-017-0490-5","article-title":"A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients","volume":"9","author":"Hall AB","year":"2017","unstructured":"Hall AB, Yassour M, Sauk J, Garner A, Jiang X, Arthur T, et al. A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med. 2017;9(1):103.","journal-title":"Genome Med"},{"issue":"11","key":"ref68","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/j.1348-0421.1985.tb00892.x","article-title":"Clostridium ramosum, an IgA Protease-Producing Species and Its Ecology in the Human Intestinal Tract","volume":"29","author":"Senda S","year":"1985","unstructured":"Senda S, Fujiyama Y, Ushijima T, Hodohara K, Bamba T, Hosoda S, et al. 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Faseb j. 2000;14(15):2380\u20132.","journal-title":"Faseb j"},{"issue":"1","key":"ref72","doi-asserted-by":"crossref","first-page":"16035","DOI":"10.1038\/sigtrans.2016.35","article-title":"Butyrate induces apoptosis by activating PDC and inhibiting complex I through SIRT3 inactivation","volume":"2","author":"Xu S","year":"2017","unstructured":"Xu S, Liu C-X, Xu W, Huang L, Zhao J-Y, Zhao S-M. Butyrate induces apoptosis by activating PDC and inhibiting complex I through SIRT3 inactivation. Signal Transduct Target Therapy. 2017;2(1):16035.","journal-title":"Signal Transduct Target Therapy"},{"issue":"51","key":"ref73","doi-asserted-by":"crossref","first-page":"12377","DOI":"10.1021\/jf504074n","article-title":"Metabolism of Kaempferia parviflora polymethoxyflavones by human intestinal bacterium Bautia sp. MRG-PMF1","volume":"62","author":"Kim M","year":"2014","unstructured":"Kim M, Kim N, Han J. 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Nutr Clin Pract. 2022;37(5):1206\u201314.","journal-title":"Nutr Clin Pract"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"671239","DOI":"10.3389\/fimmu.2021.671239","article-title":"Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates","volume":"12","author":"Bos\u00e1k J","year":"2021","unstructured":"Bos\u00e1k J, Lexa M, Fiedorov\u00e1 K, Gadara DC, Micenkov\u00e1 L, Spacil Z, et al. Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates. Front Immunol. 2021;12:671239.","journal-title":"Front Immunol"},{"year":"2021","author":"Peterson D","key":"ref80","unstructured":"Peterson D, Bonham KS, Rowland S, Pattanayak CW, Klepac-Ceraj RC. 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