The Gut and the Translocated Microbiomes in HIV Infection: Current Concepts and Future Avenues
Article Sidebar
Main Article Content
Abstract
It is widely acknowledged that HIV infection results in disruption of the gut’s mucosal integrity partly due a profound loss of gastrointestinal CD4+ T cells that are targets of the virus. In addition, systemic inflammation and immune activation that drive disease pathogenesis are reduced but not normalized by antiretroviral therapy (ART). It has long been postulated that through the process of microbial translocation, the gut microbiome acts as a key driver of systemic inflammation and immune recovery in HIV infection. As such, many studies have aimed at characterizing the gut microbiota in order to unravel its influence in people with HIV and have reported an association between various bacterial taxa and inflammation. This review assesses both contradictory and consistent findings among several studies in order to clarify the overall mechanisms by which the gut microbiota in adults may influence immune recovery in HIV infection. Independently of the gut microbiome, observations made from analysis of microbial products in the blood provide direct insight into how the translocated microbiome may drive immune recovery. To help better understand strengths and limitations of the findings reported, this review also highlights the numerous factors that can influence microbiome studies, be they experimental methodologies, and host-intrinsic or host-extrinsic factors. Altogether, a fuller understanding of the interplay between the gut microbiome and immunity in HIV infection may contribute to preventive and therapeutic approaches.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Pathogens and Immunity abides by Creative Commons BY 4.0:
http://creativecommons.org/licenses/by/4.0/
This license lets others distribute, remix, tweak, and build upon your work for any lawful purpose, even commercially, as long as they credit you for the original creation. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials. The authors maintain copyright of their materal.
*Due to a template error on our pdfs, articles published from May 20, 2016 to June 24, 2022 incorrectly state the copyright is held by Pathogens and Immunity. Copyright of all articles is held by the authors of each article as noted in the above copyright policy.
References
1. Sender R, Fuchs S, Milo R. Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell. 2016;164(3):337-40. doi: 10.1016/j.cell.2016.01.013. PubMed PMID: 26824647.
2. Marchesi JR, Ravel J. The vocabulary of microbiome research: a proposal. Microbiome. 2015;3:31. doi: 10.1186/s40168-015-0094-5. PubMed PMID: 26229597; PMCID: PMC4520061.
3. Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207-14. doi: 10.1038/nature11234. PubMed PMID: 22699609; PMCID: PMC3564958.
4. Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. Current understanding of the human microbiome. Nat Med. 2018;24(4):392-400. doi: 10.1038/nm.4517. PubMed PMID: 29634682; PMCID: PMC7043356.
5. Dabee S, Passmore JS, Heffron R, Jaspan HB. The Complex Link between the Female Genital Microbiota, Genital Infections, and Inflammation. Infect Immun. 2021;89(5). doi: 10.1128/IAI.00487-20. PubMed PMID: 33558324; PMCID: PMC8091093.
6. Kaul R, Liu CM, Park DE, Galiwango RM, Tobian AAR, Prodger JL. The Penis, the Vagina and HIV Risk: Key Differences (Aside from the Obvious). Viruses. 2022;14(6). doi: 10.3390/v14061164. PubMed PMID: 35746636; PMCID: PMC9227947.
7. Weisburg WG, Barns SM, Pelletier DA, Lane DJ. 16S ribosomal DNA amplification for phylogenetic study. J Bacteriol. 1991;173(2):697-703. doi: 10.1128/jb.173.2.697-703.1991. PubMed PMID: 1987160; PMCID: PMC207061.
8. Johnson JS, Spakowicz DJ, Hong BY, Petersen LM, Demkowicz P, Chen L, Leopold SR, Hanson BM, Agresta HO, Gerstein M, Sodergren E, Weinstock GM. Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis. Nat Commun. 2019;10(1):5029. doi: 10.1038/s41467-019-13036-1. PubMed PMID: 31695033; PMCID: PMC6834636.
9. Ranjan R, Rani A, Metwally A, McGee HS, Perkins DL. Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing. Biochem Biophys Res Commun. 2016;469(4):967-77. doi: 10.1016/j.bbrc.2015.12.083. PubMed PMID: 26718401; PMCID: PMC4830092.
10. Parks DH, Rigato F, Vera-Wolf P, Krause L, Hugenholtz P, Tyson GW, Wood DLA. Evaluation of the Microba Community Profiler for Taxonomic Profiling of Metagenomic Datasets From the Human Gut Microbiome. Front Microbiol. 2021;12:643682. doi: 10.3389/fmicb.2021.643682. PubMed PMID: 33959106; PMCID: PMC8093879.
11. Martin-Gallausiaux C, Marinelli L, Blottiere HM, Larraufie P, Lapaque N. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc. 2021;80(1):37-49. doi: 10.1017/S0029665120006916. PubMed PMID: 32238208.
12. Correa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MA. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunology. 2016;5(4):e73. doi: 10.1038/cti.2016.17. PubMed PMID: 27195116; PMCID: PMC4855267.
13. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Meta HITC, Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. doi: 10.1038/nature08821. PubMed PMID: 20203603; PMCID: PMC3779803.
14. Enriquez AB, Ten Caten F, Ghneim K, Sekaly RP, Sharma AA. Regulation of Immune Homeostasis, Inflammation, and HIV Persistence by the Microbiome, Short-Chain Fatty Acids, and Bile Acids. Annu Rev Virol. 2023;10(1):397-422. doi: 10.1146/annurev-virology-040323-082822. PubMed PMID: 37774124.
15. Salvato F, Hettich RL, Kleiner M. Five key aspects of metaproteomics as a tool to understand functional interactions in host-associated microbiomes. PLoS Pathog. 2021;17(2):e1009245. doi: 10.1371/journal.ppat.1009245. PubMed PMID: 33630960; PMCID: PMC7906368.
16. Cao S, Zhang Q, Wang C, Wu H, Jiao L, Hong Q, Hu C. LPS challenge increased intestinal permeability, disrupted mitochondrial function and triggered mitophagy of piglets. Innate Immun. 2018;24(4):221-30. doi: 10.1177/1753425918769372. PubMed PMID: 29642727; PMCID: PMC6830921.
17. Bufler P, Stiegler G, Schuchmann M, Hess S, Kruger C, Stelter F, Eckerskorn C, Schutt C, Engelmann H. Soluble lipopolysaccharide receptor (CD14) is released via two different mechanisms from human monocytes and CD14 transfectants. Eur J Immunol. 1995;25(2):604-10. doi: 10.1002/eji.1830250244. PubMed PMID: 7533093.
18. Schroder NW, Morath S, Alexander C, Hamann L, Hartung T, Zahringer U, Gobel UB, Weber JR, Schumann RR. Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J Biol Chem. 2003;278(18):15587-94. doi: 10.1074/jbc.M212829200. PubMed PMID: 12594207.
19. Gupta D, Kirkland TN, Viriyakosol S, Dziarski R. CD14 is a cell-activating receptor for bacterial peptidoglycan. J Biol Chem. 1996;271(38):23310-6. doi: 10.1074/jbc.271.38.23310. PubMed PMID: 8798531.
20. Van Amersfoort ES, Van Berkel TJ, Kuiper J. Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clin Microbiol Rev. 2003;16(3):379-414. doi: 10.1128/CMR.16.3.379-414.2003. PubMed PMID: 12857774; PMCID: PMC164216.
21. Hermann C, Spreitzer I, Schroder NW, Morath S, Lehner MD, Fischer W, Schutt C, Schumann RR, Hartung T. Cytokine induction by purified lipoteichoic acids from various bacterial species--role of LBP, sCD14, CD14 and failure to induce IL-12 and subsequent IFN-gamma release. Eur J Immunol. 2002;32(2):541-51. doi: 10.1002/1521-4141(200202)32:2<541::AID-IMMU541>3.0.CO;2-P. PubMed PMID: 11828371.
22. Landmann R, Knopf HP, Link S, Sansano S, Schumann R, Zimmerli W. Human monocyte CD14 is upregulated by lipopolysaccharide. Infect Immun. 1996;64(5):1762-9. doi: 10.1128/iai.64.5.1762-1769.1996. PubMed PMID: 8613389; PMCID: PMC173990.
23. Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, Pedersen C, Ruxrungtham K, Lewin SR, Emery S, Neaton JD, Brenchley JM, Deeks SG, Sereti I, Douek DC, Group ISS. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis. 2011;203(6):780-90. doi: 10.1093/infdis/jiq118. PubMed PMID: 21252259; PMCID: PMC3071127.
24. Kitchens RL, Thompson PA. Modulatory effects of sCD14 and LBP on LPS-host cell interactions. J Endotoxin Res. 2005;11(4):225-9. doi: 10.1179/096805105X46565. PubMed PMID: 16176659.
25. Barclay GR. Endogenous endotoxin-core antibody (EndoCAb) as a marker of endotoxin exposure and a prognostic indicator: a review. Prog Clin Biol Res. 1995;392:263-72. PubMed PMID: 8524931.
26. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4(4):e1251384. doi: 10.1080/21688370.2016.1251384. PubMed PMID: 28123927; PMCID: PMC5214347.
27. Ajamian M, Steer D, Rosella G, Gibson PR. Serum zonulin as a marker of intestinal mucosal barrier function: May not be what it seems. PLoS One. 2019;14(1):e0210728. doi: 10.1371/journal.pone.0210728. PubMed PMID: 30640940; PMCID: PMC6331146.
28. Scheffler L, Crane A, Heyne H, Tonjes A, Schleinitz D, Ihling CH, Stumvoll M, Freire R, Fiorentino M, Fasano A, Kovacs P, Heiker JT. Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family. Front Endocrinol (Lausanne). 2018;9:22. doi: 10.3389/fendo.2018.00022. PubMed PMID: 29459849; PMCID: PMC5807381.
29. Derikx JP, Luyer MD, Heineman E, Buurman WA. Non-invasive markers of gut wall integrity in health and disease. World J Gastroenterol. 2010;16(42):5272-9. doi: 10.3748/wjg.v16.i42.5272. PubMed PMID: 21072889; PMCID: PMC2980675.
30. Tincati C, Douek DC, Marchetti G. Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection. AIDS Res Ther. 2016;13:19. doi: 10.1186/s12981-016-0103-1. PubMed PMID: 27073405; PMCID: PMC4828806.
31. Chevalier MF, Petitjean G, Dunyach-Remy C, Didier C, Girard PM, Manea ME, Campa P, Meyer L, Rouzioux C, Lavigne JP, Barre-Sinoussi F, Scott-Algara D, Weiss L. The Th17/Treg ratio, IL-1RA and sCD14 levels in primary HIV infection predict the T-cell activation set point in the absence of systemic microbial translocation. PLoS Pathog. 2013;9(6):e1003453. doi: 10.1371/journal.ppat.1003453. PubMed PMID: 23818854; PMCID: PMC3688532.
32. Sereti I, Krebs SJ, Phanuphak N, Fletcher JL, Slike B, Pinyakorn S, O’Connell RJ, Rupert A, Chomont N, Valcour V, Kim JH, Robb ML, Michael NL, Douek DC, Ananworanich J, Utay NS, Rv254/Search RS, teams Sp. Persistent, Albeit Reduced, Chronic Inflammation in Persons Starting Antiretroviral Therapy in Acute HIV Infection. Clin Infect Dis. 2017;64(2):124-31. doi: 10.1093/cid/ciw683. PubMed PMID: 27737952; PMCID: PMC5215214.
33. Ancona G, Merlini E, Tincati C, Barassi A, Calcagno A, Augello M, Bono V, Bai F, Cannizzo ES, d’Arminio Monforte A, Marchetti G. Long-Term Suppressive cART Is Not Sufficient to Restore Intestinal Permeability and Gut Microbiota Compositional Changes. Front Immunol. 2021;12:639291. doi: 10.3389/fimmu.2021.639291. PubMed PMID: 33717191; PMCID: PMC7952451.
34. Reisinger KW, Elst M, Derikx JP, Nikkels PG, de Vries B, Adriaanse MP, Jellema RK, Kramer BW, Wolfs TG. Intestinal fatty acid-binding protein: a possible marker for gut maturation. Pediatr Res. 2014;76(3):261-8. doi: 10.1038/pr.2014.89. PubMed PMID: 24956227.
35. Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol. 2016;14(1):20-32. doi: 10.1038/nrmicro3552. PubMed PMID: 26499895; PMCID: PMC4837114.
36. Dillon SM, Lee EJ, Kotter CV, Austin GL, Dong Z, Hecht DK, Gianella S, Siewe B, Smith DM, Landay AL, Robertson CE, Frank DN, Wilson CC. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol. 2014;7(4):983-94. doi: 10.1038/mi.2013.116. PubMed PMID: 24399150; PMCID: PMC4062575.
37. Dinh DM, Volpe GE, Duffalo C, Bhalchandra S, Tai AK, Kane AV, Wanke CA, Ward HD. Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. J Infect Dis. 2015;211(1):19-27. doi: 10.1093/infdis/jiu409. PubMed PMID: 25057045; PMCID: PMC4326316.
38. Dubourg G, Lagier JC, Hue S, Surenaud M, Bachar D, Robert C, Michelle C, Ravaux I, Mokhtari S, Million M, Stein A, Brouqui P, Levy Y, Raoult D. Gut microbiota associated with HIV infection is significantly enriched in bacteria tolerant to oxygen. BMJ Open Gastroenterol. 2016;3(1):e000080. doi: 10.1136/bmjgast-2016-000080. PubMed PMID: 27547442; PMCID: PMC4985784.
39. Liu J, Johnson R, Dillon S, Kroehl M, Frank DN, Tuncil YE, Zhang X, Ir D, Robertson CE, Seifert S, Higgins J, Hamaker B, Wilson CC, Erlandson KM. Among older adults, age-related changes in the stool microbiome differ by HIV-1 serostatus. EBioMedicine. 2019;40:583-94. doi: 10.1016/j.ebiom.2019.01.033. PubMed PMID: 30685386; PMCID: PMC6413415.
40. Lozupone CA, Li M, Campbell TB, Flores SC, Linderman D, Gebert MJ, Knight R, Fontenot AP, Palmer BE. Alterations in the gut microbiota associated with HIV-1 infection. Cell Host Microbe. 2013;14(3):329-39. doi: 10.1016/j.chom.2013.08.006. PubMed PMID: 24034618; PMCID: PMC3864811.
41. Monaco CL, Gootenberg DB, Zhao G, Handley SA, Ghebremichael MS, Lim ES, Lankowski A, Baldridge MT, Wilen CB, Flagg M, Norman JM, Keller BC, Luevano JM, Wang D, Boum Y, Martin JN, Hunt PW, Bangsberg DR, Siedner MJ, Kwon DS, Virgin HW. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome. Cell Host Microbe. 2016;19(3):311-22. doi: 10.1016/j.chom.2016.02.011. PubMed PMID: 26962942; PMCID: PMC4821831.
42. Mutlu EA, Keshavarzian A, Losurdo J, Swanson G, Siewe B, Forsyth C, French A, Demarais P, Sun Y, Koenig L, Cox S, Engen P, Chakradeo P, Abbasi R, Gorenz A, Burns C, Landay A. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog. 2014;10(2):e1003829. doi: 10.1371/journal.ppat.1003829. PubMed PMID: 24586144; PMCID: PMC3930561.
43. Noguera-Julian M, Rocafort M, Guillen Y, Rivera J, Casadella M, Nowak P, Hildebrand F, Zeller G, Parera M, Bellido R, Rodriguez C, Carrillo J, Mothe B, Coll J, Bravo I, Estany C, Herrero C, Saz J, Sirera G, Torrela A, Navarro J, Crespo M, Brander C, Negredo E, Blanco J, Guarner F, Calle ML, Bork P, Sonnerborg A, Clotet B, Paredes R. Gut Microbiota Linked to Sexual Preference and HIV Infection. EBioMedicine. 2016;5:135-46. doi: 10.1016/j.ebiom.2016.01.032. PubMed PMID: 27077120; PMCID: PMC4816837.
44. Nowak P, Troseid M, Avershina E, Barqasho B, Neogi U, Holm K, Hov JR, Noyan K, Vesterbacka J, Svard J, Rudi K, Sonnerborg A. Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS. 2015;29(18):2409-18. doi: 10.1097/QAD.0000000000000869. PubMed PMID: 26355675.
45. Nowak RG, Bentzen SM, Ravel J, Crowell TA, Dauda W, Ma B, Liu H, Blattner WA, Baral SD, Charurat ME, Group TS. Rectal microbiota among HIV-uninfected, untreated HIV, and treated HIV-infected in Nigeria. AIDS. 2017;31(6):857-62. doi: 10.1097/QAD.0000000000001409. PubMed PMID: 28118207; PMCID: PMC5342931.
46. Perez-Santiago J, Gianella S, Massanella M, Spina CA, Karris MY, Var SR, Patel D, Jordan PS, Young JA, Little SJ, Richman DD, Smith DM. Gut Lactobacillales are associated with higher CD4 and less microbial translocation during HIV infection. AIDS. 2013;27(12):1921-31. doi: 10.1097/qad.0b013e3283611816. PubMed PMID: 24180001; PMCID: PMC3816380.
47. Pinto-Cardoso S, Lozupone C, Briceno O, Alva-Hernandez S, Tellez N, Adriana A, Murakami-Ogasawara A, Reyes-Teran G. Fecal Bacterial Communities in treated HIV infected individuals on two antiretroviral regimens. Sci Rep. 2017;7:43741. doi: 10.1038/srep43741. PubMed PMID: 28262770; PMCID: PMC5338340.
48. Rhoades N, Mendoza N, Jankeel A, Sureshchandra S, Alvarez AD, Doratt B, Heidari O, Hagan R, Brown B, Scheibel S, Marbley T, Taylor J, Messaoudi I. Altered Immunity and Microbial Dysbiosis in Aged Individuals With Long-Term Controlled HIV Infection. Front Immunol. 2019;10:463. doi: 10.3389/fimmu.2019.00463. PubMed PMID: 30915086; PMCID: PMC6423162.
49. Serrano-Villar S, Vasquez-Dominguez E, Perez-Molina JA, Sainz T, de Benito A, Latorre A, Moya A, Gosalbes MJ, Moreno S. HIV, HPV, and microbiota: partners in crime? AIDS. 2017;31(4):591-4. doi: 10.1097/QAD.0000000000001352. PubMed PMID: 27922858.
50. Serrano-Villar S, Vazquez-Castellanos JF, Vallejo A, Latorre A, Sainz T, Ferrando-Martinez S, Rojo D, Martinez-Botas J, Del Romero J, Madrid N, Leal M, Mosele JI, Motilva MJ, Barbas C, Ferrer M, Moya A, Moreno S, Gosalbes MJ, Estrada V. The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects. Mucosal Immunol. 2017;10(5):1279-93. doi: 10.1038/mi.2016.122. PubMed PMID: 28000678.
51. Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, Hernandez RD, Lederman MM, Huang Y, Somsouk M, Deeks SG, Hunt PW, Lynch SV, McCune JM. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013;5(193):193ra91. doi: 10.1126/scitranslmed.3006438. PubMed PMID: 23843452; PMCID: PMC4094294.
52. Vujkovic-Cvijin I, Sortino O, Verheij E, Sklar J, Wit FW, Kootstra NA, Sellers B, Brenchley JM, Ananworanich J, Loeff MSV, Belkaid Y, Reiss P, Sereti I. HIV-associated gut dysbiosis is independent of sexual practice and correlates with noncommunicable diseases. Nat Commun. 2020;11(1):2448. doi: 10.1038/s41467-020-16222-8. PubMed PMID: 32415070; PMCID: PMC7228978.
53. Zhao H, Feng A, Luo D, Wu H, Zhang G, Zhang L, Yuan J, Lin YF, Li L, Zou H. Altered gut microbiota is associated with different immunologic responses to antiretroviral therapy in HIV-infected men who have sex with men. J Med Virol. 2023;95(3):e28674. doi: 10.1002/jmv.28674. PubMed PMID: 36920170.
54. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM, Glickman JN, Garrett WS. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569-73. doi: 10.1126/science.1241165. PubMed PMID: 23828891; PMCID: PMC3807819.
55. Kashiwagi I, Morita R, Schichita T, Komai K, Saeki K, Matsumoto M, Takeda K, Nomura M, Hayashi A, Kanai T, Yoshimura A. Smad2 and Smad3 Inversely Regulate TGF-beta Autoinduction in Clostridium butyricum-Activated Dendritic Cells. Immunity. 2015;43(1):65-79. doi: 10.1016/j.immuni.2015.06.010. PubMed PMID: 26141582.
56. Zhang X, Yu D, Wu D, Gao X, Shao F, Zhao M, Wang J, Ma J, Wang W, Qin X, Chen Y, Xia P, Wang S. Tissue-resident Lachnospiraceae family bacteria protect against colorectal carcinogenesis by promoting tumor immune surveillance. Cell Host Microbe. 2023;31(3):418-32 e8. doi: 10.1016/j.chom.2023.01.013. PubMed PMID: 36893736.
57. Touch S, Godefroy E, Rolhion N, Danne C, Oeuvray C, Straube M, Galbert C, Brot L, Alonso Salgueiro I, Chadi S, Ledent T, Chatel JM, Langella P, Jotereau F, Altare F, Sokol H. Human CD4+CD8alpha+ Tregs induced by Faecalibacterium prausnitzii protect against intestinal inflammation. JCI Insight. 2022;7(12). doi: 10.1172/jci.insight.154722. PubMed PMID: 35536673; PMCID: PMC9309064.
58. Wang HB, Wang PY, Wang X, Wan YL, Liu YC. Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription. Dig Dis Sci. 2012;57(12):3126-35. doi: 10.1007/s10620-012-2259-4. PubMed PMID: 22684624.
59. Singh R, Chandrashekharappa S, Bodduluri SR, Baby BV, Hegde B, Kotla NG, Hiwale AA, Saiyed T, Patel P, Vijay-Kumar M, Langille MGI, Douglas GM, Cheng X, Rouchka EC, Waigel SJ, Dryden GW, Alatassi H, Zhang HG, Haribabu B, Vemula PK, Jala VR. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat Commun. 2019;10(1):89. doi: 10.1038/s41467-018-07859-7. PubMed PMID: 30626868; PMCID: PMC6327034.
60. Kullberg RFJ, Brands X, Klarenbeek AM, Butler JM, Otto NA, Faber DR, Scicluna BP, van der Poll T, Wiersinga WJ, Haak BW. Rectal microbiota are coupled with altered cytokine production capacity following community-acquired pneumonia hospitalization. iScience. 2022;25(8):104740. doi: 10.1016/j.isci.2022.104740. PubMed PMID: 35938048; PMCID: PMC9352523.
61. Litvak Y, Byndloss MX, Tsolis RM, Baumler AJ. Dysbiotic Proteobacteria expansion: a microbial signature of epithelial dysfunction. Curr Opin Microbiol. 2017;39:1-6. doi: 10.1016/j.mib.2017.07.003. PubMed PMID: 28783509.
62. Brix S, Eriksen C, Larsen JM, Bisgaard H. Metagenomic heterogeneity explains dual immune effects of endotoxins. J Allergy Clin Immunol. 2015;135(1):277-80. doi: 10.1016/j.jaci.2014.09.036. PubMed PMID: 25445821.
63. Taib N, Megrian D, Witwinowski J, Adam P, Poppleton D, Borrel G, Beloin C, Gribaldo S. Genome-wide analysis of the Firmicutes illuminates the diderm/monoderm transition. Nat Ecol Evol. 2020;4(12):1661-72. doi: 10.1038/s41559-020-01299-7. PubMed PMID: 33077930.
64. Campbell C, Sutcliffe IC, Gupta RS. Comparative proteome analysis of Acidaminococcus intestini supports a relationship between outer membrane biogenesis in Negativicutes and Proteobacteria. Arch Microbiol. 2014;196(4):307-10. doi: 10.1007/s00203-014-0964-4. PubMed PMID: 24535491.
65. Kaplan JE, Benson C, Holmes KK, Brooks JT, Pau A, Masur H, Centers for Disease C, Prevention, National Institutes of H, America HIVMAotIDSo. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR-4):1-207; quiz CE1-4. PubMed PMID: 19357635.
66. Anthony WE, Wang B, Sukhum KV, D’Souza AW, Hink T, Cass C, Seiler S, Reske KA, Coon C, Dubberke ER, Burnham CD, Dantas G, Kwon JH. Acute and persistent effects of commonly used antibiotics on the gut microbiome and resistome in healthy adults. Cell Rep. 2022;39(2):110649. doi: 10.1016/j.celrep.2022.110649. PubMed PMID: 35417701; PMCID: PMC9066705.
67. Brenchley JM, Ortiz AM. Microbiome Studies in Non-human Primates. Curr HIV/AIDS Rep. 2021;18(6):527-37. doi: 10.1007/s11904-021-00584-9. PubMed PMID: 34735686; PMCID: PMC8567131.
68. Merlini E, Tincati C, Biasin M, Saulle I, Cazzaniga FA, d’Arminio Monforte A, Cappione AJ, 3rd, Snyder-Cappione J, Clerici M, Marchetti GC. Stimulation of PBMC and Monocyte-Derived Macrophages via Toll-Like Receptor Activates Innate Immune Pathways in HIV-Infected Patients on Virally Suppressive Combination Antiretroviral Therapy. Front Immunol. 2016;7:614. doi: 10.3389/fimmu.2016.00614. PubMed PMID: 28066424; PMCID: PMC5165253.
69. Tincati C, Bellistri GM, Ancona G, Merlini E, d’Arminio Monforte A, Marchetti G. Role of in vitro stimulation with lipopolysaccharide on T-cell activation in HIV-infected antiretroviral-treated patients. Clin Dev Immunol. 2012;2012:935425. doi: 10.1155/2012/935425. PubMed PMID: 22400042; PMCID: PMC3287419.
70. Nganou-Makamdop K, Talla A, Sharma AA, Darko S, Ransier A, Laboune F, Chipman JG, Beilman GJ, Hoskuldsson T, Fourati S, Schmidt TE, Arumugam S, Lima NS, Moon D, Callisto S, Schoephoerster J, Tomalka J, Mugyenyi P, Ssali F, Muloma P, Ssengendo P, Leda AR, Cheu RK, Flynn JK, Morou A, Brunet-Ratnasingham E, Rodriguez B, Lederman MM, Kaufmann DE, Klatt NR, Kityo C, Brenchley JM, Schacker TW, Sekaly RP, Douek DC. Translocated microbiome composition determines immunological outcome in treated HIV infection. Cell. 2021;184(15):3899-914 e16. doi: 10.1016/j.cell.2021.05.023. PubMed PMID: 34237254; PMCID: PMC8316372.
71. Klase Z, Ortiz A, Deleage C, Mudd JC, Quinones M, Schwartzman E, Klatt NR, Canary L, Estes JD, Brenchley JM. Dysbiotic bacteria translocate in progressive SIV infection. Mucosal Immunol. 2015;8(5):1009-20. doi: 10.1038/mi.2014.128. PubMed PMID: 25586559; PMCID: PMC4501910.
72. Raffatellu M, Santos RL, Verhoeven DE, George MD, Wilson RP, Winter SE, Godinez I, Sankaran S, Paixao TA, Gordon MA, Kolls JK, Dandekar S, Baumler AJ. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008;14(4):421-8. doi: 10.1038/nm1743. PubMed PMID: 18376406; PMCID: PMC2901863.
73. Serrano-Villar S, Sanchez-Carrillo S, Talavera-Rodriguez A, Lelouvier B, Gutierrez C, Vallejo A, Servant F, Bernadino JI, Estrada V, Madrid N, Gosalbes MJ, Bisbal O, de Lagarde M, Martinez-Sanz J, Ron R, Herrera S, Moreno S, Ferrer M. Blood Bacterial Profiles Associated With Human Immunodeficiency Virus Infection and Immune Recovery. J Infect Dis. 2021;223(3):471-81. doi: 10.1093/infdis/jiaa379. PubMed PMID: 32601702.
74. Merlini E, Bai F, Bellistri GM, Tincati C, d’Arminio Monforte A, Marchetti G. Evidence for polymicrobic flora translocating in peripheral blood of HIV-infected patients with poor immune response to antiretroviral therapy. PLoS One. 2011;6(4):e18580. doi: 10.1371/journal.pone.0018580. PubMed PMID: 21494598; PMCID: PMC3073938.
75. Guo X, Wang Z, Qu M, Guo Y, Yu M, Hong W, Zhang C, Fan X, Song J, Xu R, Zhang J, Huang H, Linghu E, Wang FS, Sun L, Jiao YM. Abnormal blood microbiota profiles are associated with inflammation and immune restoration in HIV/AIDS individuals. mSystems. 2023;8(5):e0046723. doi: 10.1128/msystems.00467-23. PubMed PMID: 37698407; PMCID: PMC10654078.
76. Eisenhofer R, Minich JJ, Marotz C, Cooper A, Knight R, Weyrich LS. Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations. Trends Microbiol. 2019;27(2):105-17. doi: 10.1016/j.tim.2018.11.003. PubMed PMID: 30497919.
77. Li L, Wang T, Ning Z, Zhang X, Butcher J, Serrana JM, Simopoulos CMA, Mayne J, Stintzi A, Mack DR, Liu YY, Figeys D. Revealing proteome-level functional redundancy in the human gut microbiome using ultra-deep metaproteomics. Nat Commun. 2023;14(1):3428. doi: 10.1038/s41467-023-39149-2. PubMed PMID: 37301875; PMCID: PMC10257714.
78. Neff CP, Krueger O, Xiong K, Arif S, Nusbacher N, Schneider JM, Cunningham AW, Armstrong A, Li S, McCarter MD, Campbell TB, Lozupone CA, Palmer BE. Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals. EBioMedicine. 2018;30:192-202. doi: 10.1016/j.ebiom.2018.03.024. PubMed PMID: 29650491; PMCID: PMC5952409.
79. Badal VD, Vaccariello ED, Murray ER, Yu KE, Knight R, Jeste DV, Nguyen TT. The Gut Microbiome, Aging, and Longevity: A Systematic Review. Nutrients. 2020;12(12). doi: 10.3390/nu12123759. PubMed PMID: 33297486; PMCID: PMC7762384.
80. Albenberg LG, Wu GD. Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology. 2014;146(6):1564-72. doi: 10.1053/j.gastro.2014.01.058. PubMed PMID: 24503132; PMCID: PMC4216184.
81. Valeri F, Endres K. How biological sex of the host shapes its gut microbiota. Front Neuroendocrinol. 2021;61:100912. doi: 10.1016/j.yfrne.2021.100912. PubMed PMID: 33713673.
82. Deschasaux M, Bouter KE, Prodan A, Levin E, Groen AK, Herrema H, Tremaroli V, Bakker GJ, Attaye I, Pinto-Sietsma SJ, van Raalte DH, Snijder MB, Nicolaou M, Peters R, Zwinderman AH, Backhed F, Nieuwdorp M. Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography. Nat Med. 2018;24(10):1526-31. doi: 10.1038/s41591-018-0160-1. PubMed PMID: 30150717.
83. He Y, Wu W, Zheng HM, Li P, McDonald D, Sheng HF, Chen MX, Chen ZH, Ji GY, Zheng ZD, Mujagond P, Chen XJ, Rong ZH, Chen P, Lyu LY, Wang X, Wu CB, Yu N, Xu YJ, Yin J, Raes J, Knight R, Ma WJ, Zhou HW. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat Med. 2018;24(10):1532-5. doi: 10.1038/s41591-018-0164-x. PubMed PMID: 30150716.
84. Kurilshikov A, Medina-Gomez C, Bacigalupe R, Radjabzadeh D, Wang J, Demirkan A, Le Roy CI, Raygoza Garay JA, Finnicum CT, Liu X, Zhernakova DV, Bonder MJ, Hansen TH, Frost F, Ruhlemann MC, Turpin W, Moon JY, Kim HN, Lull K, Barkan E, Shah SA, Fornage M, Szopinska-Tokov J, Wallen ZD, Borisevich D, Agreus L, Andreasson A, Bang C, Bedrani L, Bell JT, Bisgaard H, Boehnke M, Boomsma DI, Burk RD, Claringbould A, Croitoru K, Davies GE, van Duijn CM, Duijts L, Falony G, Fu J, van der Graaf A, Hansen T, Homuth G, Hughes DA, Ijzerman RG, Jackson MA, Jaddoe VWV, Joossens M, Jorgensen T, Keszthelyi D, Knight R, Laakso M, Laudes M, Launer LJ, Lieb W, Lusis AJ, Masclee AAM, Moll HA, Mujagic Z, Qibin Q, Rothschild D, Shin H, Sorensen SJ, Steves CJ, Thorsen J, Timpson NJ, Tito RY, Vieira-Silva S, Volker U, Volzke H, Vosa U, Wade KH, Walter S, Watanabe K, Weiss S, Weiss FU, Weissbrod O, Westra HJ, Willemsen G, Payami H, Jonkers D, Arias Vasquez A, de Geus EJC, Meyer KA, Stokholm J, Segal E, Org E, Wijmenga C, Kim HL, Kaplan RC, Spector TD, Uitterlinden AG, Rivadeneira F, Franke A, Lerch MM, Franke L, Sanna S, D’Amato M, Pedersen O, Paterson AD, Kraaij R, Raes J, Zhernakova A. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet. 2021;53(2):156-65. doi: 10.1038/s41588-020-00763-1. PubMed PMID: 33462485; PMCID: PMC8515199.
85. Denny JE, Powell WL, Schmidt NW. Local and Long-Distance Calling: Conversations between the Gut Microbiota and Intra- and Extra-Gastrointestinal Tract Infections. Front Cell Infect Microbiol. 2016;6:41. doi: 10.3389/fcimb.2016.00041. PubMed PMID: 27148490; PMCID: PMC4826874.
86. Stefanetti G, Kasper DL. Impact of the Host Microbiome on Vaccine Responsiveness: Lessons Learned and Future Perspective. Biochemistry. 2022;61(24):2849-55. doi: 10.1021/acs.biochem.2c00309. PubMed PMID: 35993915; PMCID: PMC9782311.
87. Rani V, Singhal S, Sharma K, Vaid R, Aggarwal K, Bhadana R, Agarwal R, Atale N. Human Gut Microbiome: A New Frontier in Cancer Diagnostics & Therapeutics. Curr Pharm Des. 2021;27(45):4578-92. doi: 10.2174/1381612827666211006152112. PubMed PMID: 34620056.
88. Islam MZ, Tran M, Xu T, Tierney BT, Patel C, Kostic AD. Reproducible and opposing gut microbiome signatures distinguish autoimmune diseases and cancers: a systematic review and meta-analysis. Microbiome. 2022;10(1):218. doi: 10.1186/s40168-022-01373-1. PubMed PMID: 36482486; PMCID: PMC9733034.
89. Sepich-Poore GD, Zitvogel L, Straussman R, Hasty J, Wargo JA, Knight R. The microbiome and human cancer. Science. 2021;371(6536). doi: 10.1126/science.abc4552. PubMed PMID: 33766858; PMCID: PMC8767999.
90. Fu YS, Chu QS, Ashuro AA, Di DS, Zhang Q, Liu XM, Fan YG. The Effect of Probiotics, Prebiotics, and Synbiotics on CD4 Counts in HIV-Infected Patients: A Systematic Review and Meta-Analysis. Biomed Res Int. 2020;2020:7947342. doi: 10.1155/2020/7947342. PubMed PMID: 33294453; PMCID: PMC7718054.