Antibiotic-resistant bacteria originating from the gut may modulate the mucosal immune response during sepsis and septic shock

Authors

DOI:

https://doi.org/10.33393/dti.2022.2520

Keywords:

Immune response, Inflammation, Metabolites, Microbiota, Sepsis

Abstract

The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and diversity in sepsis and septic shock has not yet been characterized. The impact of gut microbiota diversity on host immunological disorders and future treatments of inflammatory diseases are not yet characterized. Further, the association between the microbiota and immune development in sepsis remains unknown, and the underlying mechanisms are not well understood. The altered composition of gut microbiota during sepsis is profoundly associated with a loss of commensal bacteria and an overgrowth of potentially pathogenic bacteria; especially antibiotics resistance bacteria. The altered composition and diversity of gut microbiota especially AMR bacteria due to treatment with antibiotics may lead to the translocation of enteric bacteria across the epithelium and causes the pathogenesis of sepsis. Disruptions of gut microbiota diversity are directly associated with susceptibility to sepsis and a higher risk of adverse outcomes. Several studies have confirmed that a mutual association between gut microbiota and the host is important for the metabolism of essential nutrients for the organism, for gut development, and the maturation and development of a fully functional immune system. Therefore, depth knowledge of the gut microbiota diversity, composition, and function during various inflammatory conditions and sepsis may provide a comprehensive understanding of the mechanisms behind the pathogenesis of gut-derived infection in diseases and the design of new treatment options (e.g., probiotics or fecal microbiota transplantation).

Emerging evidence display an important role of gut microbiota and their derived metabolites in modulating the host mucosal immune response and determining the susceptibility to, as well as outcomes of sepsis.

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Author Biographies

Swinder Jeet Singh Kalra, D.A-V Kanpur, Uttar Pradesh - India

DAV Kanpur, Uttar Pradesh, India

Hari Shankar, Indian Council of Medical Research (ICMR), New Delhi - India

Indian Council of Medical Research (ICMR), New Delhi, India

Nasim Mansoori, All India Institute of Medical Sciences (AIIMS), New Delhi - India

All India Institute of Medical Sciences (AIIMS), New Delhi, India

References

Bhopale GM. Antimicrobial peptides: a promising avenue for human healthcare. Curr Pharm Biotechnol. 2020;21(2):90-96. https://doi.org/10.2174/1389201020666191011121722PMID:31612826 DOI: https://doi.org/10.2174/1389201020666191011121722

Droz N, Hsia Y, Ellis S, Dramowski A, Sharland M, Basmaci R. Bacterial pathogens and resistance causing community acquired paediatric bloodstream infections in low- and middle-income countries: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2019;8(1):207. https://doi.org/10.1186/s13756-019-0673-5 PMID:31893041 DOI: https://doi.org/10.1186/s13756-019-0673-5

Samreen, Ahmad I, Malak HA, Abulreesh HH. Environmental antimicrobial resistance and its drivers: a potential threat to public health. J Glob Antimicrob Resist. 2021;27:101-111. https://doi.org/10.1016/j.jgar.2021.08.001 PMID:34454098 DOI: https://doi.org/10.1016/j.jgar.2021.08.001

Brinkac L, Voorhies A, Gomez A, Nelson KE. The threat of antimicrobial resistance on the human microbiome. Microb Ecol. 2017;74(4):1001-1008. https://doi.org/10.1007/s00248-017-0985-z PMID:28492988 DOI: https://doi.org/10.1007/s00248-017-0985-z

Unemo M, Lahra MM, Escher M, et al. WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017-18: a retrospective observational study. Lancet Microbe. 2021;2(11):e627-e636. https://doi.org/10.1016/S2666-5247(21)00171-3 PMID:35544082 DOI: https://doi.org/10.1016/S2666-5247(21)00171-3

Diallo OO, Baron SA, Abat C, Colson P, Chaudet H, Rolain JM. Antibiotic resistance surveillance systems: a review. J Glob Antimicrob Resist. 2020;23:430-438. https://doi.org/10.1016/j.jgar.2020.10.009 PMID:33176216 DOI: https://doi.org/10.1016/j.jgar.2020.10.009

Naylor NR, Atun R, Zhu N, et al. Estimating the burden of antimicrobial resistance: a systematic literature review. Antimicrob Resist Infect Control. 2018;7(1):58. https://doi.org/10.1186/s13756-018-0336-y PMID:29713465 DOI: https://doi.org/10.1186/s13756-018-0336-y

Paladino JA, Sunderlin JL, Price CS, Schentag JJ. Economic consequences of antimicrobial resistance. Surg Infect (Larchmt). 2002;3(3):259-267. https://doi.org/10.1089/109629602761624225 PMID:12542927 DOI: https://doi.org/10.1089/109629602761624225

Murray CJL, Ikuta KS, Sharara F, et al; Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629-655. https://doi.org/10.1016/S0140-6736(21)02724-0 PMID:35065702 DOI: https://doi.org/10.1016/S0140-6736(21)02724-0

Bhardwaj N, Mathur P, Behera B, Mathur K, Kapil A, Misra MC. Antimicrobial resistance in beta-haemolytic streptococci in India: a four-year study. Indian J Med Res. 2018;147(1):81-87. https://doi.org/10.4103/ijmr.IJMR_1517_16 PMID:29749365 DOI: https://doi.org/10.4103/ijmr.IJMR_1517_16

Veeraraghavan B, Walia K. Antimicrobial susceptibility profile & resistance mechanisms of Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens from India. Indian J Med Res. 2019;149(2):87-96. https://doi.org/10.4103/ijmr.IJMR_214_18PMID:31219073 DOI: https://doi.org/10.4103/ijmr.IJMR_214_18

Broom A, Doron A. Antimicrobial resistance, politics, and practice in India. Qual Health Res. 2020;30(11):1684-1696. https://doi.org/10.1177/1049732320919088 PMID:32458726 DOI: https://doi.org/10.1177/1049732320919088

Ramachandran R, Muniyandi M. Rapid molecular diagnostics for multi-drug resistant tuberculosis in India. Expert Rev Anti Infect Ther. 2018;16(3):197-204. https://doi.org/10.1080/14787210.2018.1438262 PMID:29406800 DOI: https://doi.org/10.1080/14787210.2018.1438262

Stoll BJ, Puopolo KM, Hansen NI, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early-onset neonatal sepsis 2015 to 2017, the rise of Escherichia coli, and the need for novel prevention strategies. JAMA Pediatr. 2020;174(7):e200593. https://doi.org/10.1001/jamapediatrics.2020.0593 PMID:32364598 DOI: https://doi.org/10.1001/jamapediatrics.2020.0593

Mutua F, Sharma G, Grace D, Bandyopadhyay S, Shome B, Lindahl J. A review of animal health and drug use practices in India, and their possible link to antimicrobial resistance. Antimicrob Resist Infect Control. 2020;9(1):103. https://doi.org/10.1186/s13756-020-00760-3PMID:32641109 DOI: https://doi.org/10.1186/s13756-020-00760-3

Verma A, Sahay S. Healthcare needs and programmatic gaps in transition from pediatric to adult care of vertically transmitted HIV infected adolescents in India. PLoS One. 2019;14(10):e0224490. https://doi.org/10.1371/journal.pone.0224490 PMID:31661535 DOI: https://doi.org/10.1371/journal.pone.0224490

Adelman MW, Woodworth MH, Langelier C, et al. The gut microbiome’s role in the development, maintenance, and outcomes of sepsis. Crit Care. 2020;24(1):278. https://doi.org/10.1186/s13054-020-02989-1 PMID:32487252 DOI: https://doi.org/10.1186/s13054-020-02989-1

Scheithauer TPM, Rampanelli E, Nieuwdorp M, et al. Gut microbiota as a trigger for metabolic inflammation in obesity and type 2 diabetes. Front Immunol. 2020;11:571731. https://doi.org/10.3389/fimmu.2020.571731 PMID:33178196 DOI: https://doi.org/10.3389/fimmu.2020.571731

Chen Y, Zhou J, Wang L. Role and mechanism of gut microbiota in human disease. Front Cell Infect Microbiol. 2021;11:625913. https://doi.org/10.3389/fcimb.2021.625913PMID:33816335 DOI: https://doi.org/10.3389/fcimb.2021.625913

Haak BW, Wiersinga WJ. The role of the gut microbiota in sepsis. Lancet Gastroenterol Hepatol. 2017;2(2):135-143. https://doi.org/10.1016/S2468-1253(16)30119-4 PMID:28403983 DOI: https://doi.org/10.1016/S2468-1253(16)30119-4

Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019;76(3):473-493. https://doi.org/10.1007/s00018-018-2943-4 PMID:30317530 DOI: https://doi.org/10.1007/s00018-018-2943-4

Hills RD Jr, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut microbiome: profound implications for diet and disease. Nutrients. 2019;11(7):E1613. https://doi.org/10.3390/nu11071613 PMID:31315227 DOI: https://doi.org/10.3390/nu11071613

Sakkas H, Bozidis P, Touzios C, et al. Nutritional status and the influence of the vegan diet on the gut microbiota and human health. Medicina (Kaunas). 2020;56(2):88. https://doi.org/10.3390/medicina56020088 PMID:32098430 DOI: https://doi.org/10.3390/medicina56020088

Amoroso C, Perillo F, Strati F, Fantini MC, Caprioli F, Facciotti F. The role of gut microbiota biomodulators on mucosal immunity and intestinal inflammation. Cells. 2020;9(5):E1234. https://doi.org/10.3390/cells9051234 PMID:32429359 DOI: https://doi.org/10.3390/cells9051234

Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie van Leeuwenhoek. 2020;113(12):2019-2040. https://doi.org/10.1007/s10482-020-01474-7PMID:33136284 DOI: https://doi.org/10.1007/s10482-020-01474-7

Leclercq S, Matamoros S, Cani PD, et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proc Natl Acad Sci USA. 2014;111(42):E4485-E4493. https://doi.org/10.1073/pnas.1415174111 PMID:25288760 DOI: https://doi.org/10.1073/pnas.1415174111

Marizzoni M, Cattaneo A, Mirabelli P, et al. Short-chain fatty acids and lipopolysaccharide as mediators between gut dysbiosis and amyloid pathology in Alzheimer’s disease. J Alzheimers Dis. 2020;78(2):683-697. https://doi.org/10.3233/JAD-200306 PMID:33074224 DOI: https://doi.org/10.3233/JAD-200306

Dinan TG, Cryan JF. The microbiome-gut-brain axis in health and disease. Gastroenterol Clin North Am. 2017;46(1):77-89. https://doi.org/10.1016/j.gtc.2016.09.007 PMID:28164854 DOI: https://doi.org/10.1016/j.gtc.2016.09.007

Fleischmann C, Scherag A, Adhikari NKJ, et al; International Forum of Acute Care Trialists. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med. 2016;193(3):259-272. https://doi.org/10.1164/rccm.201504-0781OC PMID:26414292 DOI: https://doi.org/10.1164/rccm.201504-0781OC

Rhee C, Jones TM, Hamad Y, et al; Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program. Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals. JAMA Netw Open. 2019;2(2):e187571. https://doi.org/10.1001/jamanetworkopen.2018.7571 PMID:30768188 DOI: https://doi.org/10.1001/jamanetworkopen.2018.7571

Rossaint J, Zarbock A. Pathogenesis of multiple organ failure in sepsis. Crit Rev Immunol. 2015;35(4):277-291. https://doi.org/10.1615/CritRevImmunol.2015015461 PMID:26757392 DOI: https://doi.org/10.1615/CritRevImmunol.2015015461

Gupta DL, Bhoi S, Mohan T, Galwnkar S, Rao DN. Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with post traumatic sepsis. Cytokine. 2016;88:214-221. https://doi.org/10.1016/j.cyto.2016.09.010 PMID:27676155 DOI: https://doi.org/10.1016/j.cyto.2016.09.010

Gupta DL, Sharma A, Soni KD, Kazim SN, Bhoi S, Rao DN. Changes in the behaviour of monocyte subsets in acute post-traumatic sepsis patients. Mol Immunol. 2021;136:65-72. https://doi.org/10.1016/j.molimm.2021.04.005 PMID:34087625 DOI: https://doi.org/10.1016/j.molimm.2021.04.005

Chen R, Wang J, Zhan R, Zhang L, Wang X. Fecal metabonomics combined with 16S rRNA gene sequencing to analyze the changes of gut microbiota in rats with kidney-yang deficiency syndrome and the intervention effect of You-gui pill. J Ethnopharmacol. 2019;244:112139. https://doi.org/10.1016/j.jep.2019.112139 PMID:31401318 DOI: https://doi.org/10.1016/j.jep.2019.112139

Zhou X, Li J, Guo J, et al. Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction. Microbiome. 2018;6(1):66. https://doi.org/10.1186/s40168-018-0441-4 PMID:29615110 DOI: https://doi.org/10.1186/s40168-018-0441-4

Becattini S, Taur Y, Pamer EG. Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol Med. 2016;22(6):458-478. https://doi.org/10.1016/j.molmed.2016.04.003PMID:27178527 DOI: https://doi.org/10.1016/j.molmed.2016.04.003

Shimizu K, Yamada T, Ogura H, et al. Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: a randomized controlled trial. Crit Care. 2018;22(1):239. https://doi.org/10.1186/s13054-018-2167-x PMID:30261905 DOI: https://doi.org/10.1186/s13054-018-2167-x

Lange K, Buerger M, Stallmach A, Bruns T. Effects of antibiotics on gut microbiota. Dig Dis. 2016;34(3):260-268. https://doi.org/10.1159/000443360 PMID:27028893 DOI: https://doi.org/10.1159/000443360

Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 2015;33(9):496-503. https://doi.org/10.1016/j.tibtech.2015.06.011PMID:26210164 DOI: https://doi.org/10.1016/j.tibtech.2015.06.011

Graspeuntner S, Waschina S, Künzel S, et al. Gut dysbiosis with bacilli dominance and accumulation of fermentation products precedes late-onset sepsis in preterm infants. Clin Infect Dis. 2019;69(2):268-277. https://doi.org/10.1093/cid/ciy882 PMID:30329017 DOI: https://doi.org/10.1093/cid/ciy882

Hoytema van Konijnenburg DP, Reis BS, Pedicord VA, Farache J, Victora GD, Mucida D. Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection. Cell. 2017;171(4):783-794.e13. https://doi.org/10.1016/j.cell.2017.08.046PMID:28942917 DOI: https://doi.org/10.1016/j.cell.2017.08.046

Saez A, Gomez-Bris R, Herrero-Fernandez B, Mingorance C, Rius C, Gonzalez-Granado JM. Innate lymphoid cells in intestinal homeostasis and inflammatory bowel disease. Int J Mol Sci. 2021;22(14):7618. https://doi.org/10.3390/ijms22147618 PMID:34299236 DOI: https://doi.org/10.3390/ijms22147618

Li Y, Jin L, Chen T. The effects of secretory IgA in the mucosal immune system. BioMed Res Int. 2020;2020:2032057. https://doi.org/10.1155/2020/2032057 PMID:31998782 DOI: https://doi.org/10.1155/2020/2032057

Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe. 2018;23(6):716-724. https://doi.org/10.1016/j.chom.2018.05.003 PMID:29902437 DOI: https://doi.org/10.1016/j.chom.2018.05.003

Ma H, Qiu Y, Yang H. Intestinal intraepithelial lymphocytes: maintainers of intestinal immune tolerance and regulators of intestinal immunity. J Leukoc Biol. 2021;109(2):339-347. https://doi.org/10.1002/JLB.3RU0220-111 PMID:32678936 DOI: https://doi.org/10.1002/JLB.3RU0220-111

Panda SK, Colonna M. Innate lymphoid cells in mucosal immunity. Front Immunol. 2019;10:861. https://doi.org/10.3389/fimmu.2019.00861 PMID:31134050 DOI: https://doi.org/10.3389/fimmu.2019.00861

Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science. 2016;352(6285):539-544. https://doi.org/10.1126/science.aad9378 PMID:27126036 DOI: https://doi.org/10.1126/science.aad9378

Hapfelmeier S, Lawson MAE, Slack E, et al. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science. 2010;328(5986):1705-1709. https://doi.org/10.1126/science.1188454 PMID:20576892 DOI: https://doi.org/10.1126/science.1188454

Hernández-Chirlaque C, Aranda CJ, Ocón B, et al. Germ-free and antibiotic-treated mice are highly susceptible to epithelial injury in DSS colitis. J Crohn’s Colitis. 2016;10(11):1324-1335. https://doi.org/10.1093/ecco-jcc/jjw096 PMID:27117829 DOI: https://doi.org/10.1093/ecco-jcc/jjw096

Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341-352. https://doi.org/10.1038/nri.2016.42 PMID:27231050 DOI: https://doi.org/10.1038/nri.2016.42

Published

2022-12-31

How to Cite

Kalra, S. J. S., Hari Shankar, Nasim Mansoori, & Gupta, D. L. (2022). Antibiotic-resistant bacteria originating from the gut may modulate the mucosal immune response during sepsis and septic shock. Drug Target Insights, 16(1), 81–87. https://doi.org/10.33393/dti.2022.2520

Issue

Section

Focus on Antimicrobial Resistance (AMR)

Categories

Received 2022-11-16
Accepted 2022-12-30
Published 2022-12-31

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