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Gut microbiota diversity of hospitalized older adult patients with and without antibiotic-associated diarrhea

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Abstract

Background

The incidence of antibiotic-related diarrhea (AAD) is high in older adults.

Aim

To examine the gut microbiota changes in older adults who received antibiotics to identify the microbial signatures associated with antibiotic use and AAD.

Methods

A nested prospective observational cohort study was conducted between December 2019 and June 2021 in patients ≥ 65 years old at Huashan Hospital affiliated with Fudan University. The patients were grouped as antibiotic-treated (HA group) and no antibiotics (HC group); the HA group was subdivided as with vs. without AAD. Fecal samples were collected at admission (i.e., before eventual antibiotics) and after 7 days.

Result

Thirty-eight and 19 participants were included in the HA and HC groups. There were significant differences in gut microbiota between the HA after antibiotics vs. HC groups, with a higher Firmicutes/Bacteroidetes ratio. Before antibiotics in the HA group, the relative abundances of Akkermansia and Alistipes were lower in the AAD subgroup than the no-AAD subgroup, while the relative abundance of Actinomyces was higher. After antibiotics in the HA group, specific bacterial species were decreased in the AAD subgroup compared with the no-AAD subgroup. Among HA participants without probiotics, the abundance of Akkermansia in the patients without AAD was higher than in the patients with AAD at baseline (P = 0.007).

Conclusion

Patients with or without AAD have different gut microbiota compositions before antibiotics. Antibiotics can lead to dysbiosis, with a decrease in beneficial bacteria and an increase in Enterococcus.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article.

References

  1. Giannelli FR (2017) Antibiotic-associated diarrhea. JAAPA 30:46–47. https://doi.org/10.1097/01.JAA.0000524721.01579.c9

    Article  PubMed  Google Scholar 

  2. Kyne L, Warny M, Qamar A et al (2000) Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 342:390–397. https://doi.org/10.1056/NEJM200002103420604

    Article  CAS  PubMed  Google Scholar 

  3. Furuya-Kanamori L, Marquess J, Yakob L et al (2015) Asymptomatic Clostridium difficile colonization: epidemiology and clinical implications. BMC Infect Dis 15:516. https://doi.org/10.1186/s12879-015-1258-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hicks LA, Bartoces MG, Roberts RM et al (2015) US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011. Clin Infect Dis 60:1308–1316. https://doi.org/10.1093/cid/civ076

    Article  PubMed  Google Scholar 

  5. Arizpe A, Reveles KR, Aitken SL (2016) Regional variation in antibiotic prescribing among medicare part D enrollees, 2013. BMC Infect Dis 16:744. https://doi.org/10.1186/s12879-016-2091-0

    Article  PubMed  PubMed Central  Google Scholar 

  6. Shin JH, High KP, Warren CA (2016) Older is not wiser, immunologically speaking: effect of aging on host response to Clostridium difficile infections. J Gerontol A Biol Sci Med Sci 71:916–922. https://doi.org/10.1093/gerona/glv229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cohen SH, Gerding DN, Johnson S et al (2010) Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 31:431–455. https://doi.org/10.1086/651706

    Article  PubMed  Google Scholar 

  8. Gill SR, Pop M, Deboy RT et al (2006) Metagenomic analysis of the human distal gut microbiome. Science 312:1355–1359. https://doi.org/10.1126/science.1124234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Claesson MJ, Cusack S, O’Sullivan O et al (2011) Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci U S A 108:4586–4591. https://doi.org/10.1073/pnas.1000097107

    Article  PubMed  Google Scholar 

  10. Claesson MJ, Jeffery IB, Conde S et al (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488:178–184. https://doi.org/10.1038/nature11319

    Article  CAS  PubMed  Google Scholar 

  11. Salazar N, Lopez P, Valdes L et al (2013) Microbial targets for the development of functional foods accordingly with nutritional and immune parameters altered in the elderly. J Am Coll Nutr 32:399–406. https://doi.org/10.1080/07315724.2013.827047

    Article  CAS  PubMed  Google Scholar 

  12. Ragonnaud E, Biragyn A (2021) Gut microbiota as the key controllers of “healthy” aging of elderly people. Immun Ageing 18:2. https://doi.org/10.1186/s12979-020-00213-w

    Article  PubMed  PubMed Central  Google Scholar 

  13. Dogra SK, Dore J, Damak S (2020) Gut microbiota resilience: definition, link to health and strategies for intervention. Front Microbiol 11:572921. https://doi.org/10.3389/fmicb.2020.572921

    Article  PubMed  PubMed Central  Google Scholar 

  14. O’Toole PW, Jeffery IB (2015) Gut microbiota and aging. Science 350:1214–1215. https://doi.org/10.1126/science.aac8469

    Article  CAS  PubMed  Google Scholar 

  15. O’Sullivan O, Coakley M, Lakshminarayanan B et al (2013) Alterations in intestinal microbiota of elderly Irish subjects post-antibiotic therapy. J Antimicrob Chemother 68:214–221. https://doi.org/10.1093/jac/dks348

    Article  CAS  PubMed  Google Scholar 

  16. Bartosch S, Fite A, Macfarlane GT et al (2004) Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol 70:3575–3581. https://doi.org/10.1128/AEM.70.6.3575-3581.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jeffery IB, Lynch DB, O’Toole PW (2016) Composition and temporal stability of the gut microbiota in older persons. ISME J 10:170–182. https://doi.org/10.1038/ismej.2015.88

    Article  CAS  PubMed  Google Scholar 

  18. Clark RI, Salazar A, Yamada R et al (2015) Distinct shifts in microbiota composition during Drosophila aging impair intestinal function and drive mortality. Cell Rep 12:1656–1667. https://doi.org/10.1016/j.celrep.2015.08.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. McFarland LV (2008) Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol 3:563–578. https://doi.org/10.2217/17460913.3.5.563

    Article  PubMed  Google Scholar 

  20. Rinninella E, Raoul P, Cintoni M et al (2019) What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms. https://doi.org/10.3390/microorganisms7010014

    Article  PubMed  PubMed Central  Google Scholar 

  21. Panda S, El khader I, Casellas F et al (2014) Short-term effect of antibiotics on human gut microbiota. PLoS One 9:e95476. https://doi.org/10.1371/journal.pone.0095476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lloyd-Price J, Arze C, Ananthakrishnan AN et al (2019) Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569:655–662. https://doi.org/10.1038/s41586-019-1237-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Parnanen K, Karkman A, Hultman J et al (2018) Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements. Nat Commun 9:3891. https://doi.org/10.1038/s41467-018-06393-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gasparrini AJ, Wang B, Sun X et al (2019) Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome. Nat Microbiol 4:2285–2297. https://doi.org/10.1038/s41564-019-0550-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Elvers KT, Wilson VJ, Hammond A et al (2020) Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK: a systematic review. BMJ Open 10:e035677. https://doi.org/10.1136/bmjopen-2019-035677

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ramirez J, Guarner F, Bustos Fernandez L et al (2020) Antibiotics as major disruptors of gut microbiota. Front Cell Infect Microbiol 10:572912. https://doi.org/10.3389/fcimb.2020.572912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rashid MU, Zaura E, Buijs MJ et al (2015) Determining the long-term effect of antibiotic administration on the human normal intestinal microbiota using culture and pyrosequencing methods. Clin Infect Dis 60:S77-84. https://doi.org/10.1093/cid/civ137

    Article  CAS  PubMed  Google Scholar 

  28. Allen SJ, Wareham K, Wang D et al (2013) Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 382:1249–1257. https://doi.org/10.1016/S0140-6736(13)61218-0

    Article  PubMed  Google Scholar 

  29. Jafarnejad S, Shab-Bidar S, Speakman JR et al (2016) Probiotics reduce the risk of antibiotic-associated diarrhea in adults (18–64 years) but not the elderly (>65 years): a meta-analysis. Nutr Clin Pract 31:502–513. https://doi.org/10.1177/0884533616639399

    Article  PubMed  Google Scholar 

  30. Lee KJ, Kim JH, Cho SW (2005) Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 22:981–988. https://doi.org/10.1111/j.1365-2036.2005.02685.x

    Article  CAS  PubMed  Google Scholar 

  31. Rondanelli M, Faliva MA, Perna S et al (2017) Using probiotics in clinical practice: where are we now? A review of existing meta-analyses. Gut Microbes 8:521–543. https://doi.org/10.1080/19490976.2017.1345414

    Article  PubMed  PubMed Central  Google Scholar 

  32. Krawczyk B, Wityk P, Galecka M et al (2021) The many faces of Enterococcus spp.-commensal, probiotic and opportunistic pathogen. Microorganisms. https://doi.org/10.3390/microorganisms9091900

    Article  PubMed  PubMed Central  Google Scholar 

  33. Gu X, Sim JXY, Lee WL et al (2022) Gut Ruminococcaceae levels at baseline correlate with risk of antibiotic-associated diarrhea. iScience 25:103644. https://doi.org/10.1016/j.isci.2021.103644

    Article  CAS  PubMed  Google Scholar 

  34. Konikoff T, Gophna U (2016) Oscillospira: a central, enigmatic component of the human gut microbiota. Trends Microbiol 24:523–524. https://doi.org/10.1016/j.tim.2016.02.015

    Article  CAS  PubMed  Google Scholar 

  35. Feng W, Liu J, Ao H et al (2020) Targeting gut microbiota for precision medicine: focusing on the efficacy and toxicity of drugs. Theranostics 10:11278–11301. https://doi.org/10.7150/thno.47289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rodrigues VF, Elias-Oliveira J, Pereira IS et al (2022) Akkermansia muciniphila and gut immune system: a good friendship that attenuates inflammatory bowel disease, obesity, and diabetes. Front Immunol 13:934695. https://doi.org/10.3389/fimmu.2022.934695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhou K (2017) Strategies to promote abundance of Akkermansia muciniphila, an emerging probiotics in the gut, evidence from dietary intervention studies. J Funct Foods 33:194–201. https://doi.org/10.1016/j.jff.2017.03.045

    Article  PubMed  PubMed Central  Google Scholar 

  38. Daniel N, Gewirtz AT, Chassaing B (2023) Akkermansia muciniphila counteracts the deleterious effects of dietary emulsifiers on microbiota and host metabolism. Gut. https://doi.org/10.1136/gutjnl-2021-326835

    Article  PubMed  Google Scholar 

  39. Wu Z, Xu Q, Gu S et al (2022) Akkermansia muciniphila ameliorates Clostridioides difficile infection in mice by modulating the intestinal microbiome and metabolites. Front Microbiol 13:841920. https://doi.org/10.3389/fmicb.2022.841920

    Article  PubMed  PubMed Central  Google Scholar 

  40. Xiang XW, Wang R, Yao LW et al (2021) Anti-inflammatory effects of Mytilus coruscus polysaccharide on RAW264.7 cells and DSS-induced colitis in mice. Mar Drugs. https://doi.org/10.3390/md19080468

    Article  PubMed  PubMed Central  Google Scholar 

  41. Hsiao YC, Lee YH, Ho CM et al (2021) Clinical characteristics of Actinomyces viscosus Bacteremia. Medicina (Kaunas). https://doi.org/10.3390/medicina57101064

    Article  PubMed  PubMed Central  Google Scholar 

  42. Korf JM, Ganesh BP, McCullough LD (2022) Gut dysbiosis and age-related neurological diseases in females. Neurobiol Dis 168:105695. https://doi.org/10.1016/j.nbd.2022.105695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Holmes A, Finger C, Morales-Scheihing D et al (2020) Gut dysbiosis and age-related neurological diseases; an innovative approach for therapeutic interventions. Transl Res 226:39–56. https://doi.org/10.1016/j.trsl.2020.07.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Buford TW (2017) (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome 5:80. https://doi.org/10.1186/s40168-017-0296-0

    Article  PubMed  PubMed Central  Google Scholar 

  45. Koppie TM, Serio AM, Vickers AJ et al (2008) Age-adjusted Charlson comorbidity score is associated with treatment decisions and clinical outcomes for patients undergoing radical cystectomy for bladder cancer. Cancer 112:2384–2392. https://doi.org/10.1002/cncr.23462

    Article  PubMed  Google Scholar 

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Funding

This work was supported by the clinical project of the Shanghai Municipal Health Commission (No. 201940312) and Shanghai Municipal Key Clinical Specialty (Geriatrics, No. shslczdzk02802).

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Author notes

  1. Lanlan Zhao, Yu Zhang, and Hui Qiao have contributed equally to this work.

Authors and Affiliations

  1. Department of Gerontology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China

    Lanlan Zhao, Yu Zhang, Yuezhi Wang & Jiaoqi Ren

  2. Department of Anesthesiology, Eye and ENT Hospital, Fudan University, Shanghai, 200031, China

    Hui Qiao

  3. Department of General Medicine, Xinzhuang Community Health Service Center, Shanghai, 201199, China

    Yan Wang

  4. Department of Gerontology, Shanghai Sixth People’s Hospital Jinshan Branch, Shanghai, 201500, China

    Jian Zhao

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  1. Lanlan Zhao
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Contributions

YW, YW, and JR carried out the studies, participated in collecting data, and drafted the manuscript. YW, YZ, and JZ performed the statistical analysis and participated in its design. LZ and HQ participated in the acquisition, analysis, or interpretation of data and drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yuezhi Wang.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval and consent to participate

This study was approved by the Clinical Research Ethics Committee of Huashan Hospital (KY2018-437). Informed consent was obtained from all subjects or, in cases of cognitive impairment, next of kin, in accordance with the Ethics Committee’s guidelines.

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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zhao, L., Zhang, Y., Wang, Y. et al. Gut microbiota diversity of hospitalized older adult patients with and without antibiotic-associated diarrhea. Aging Clin Exp Res 35, 1541–1555 (2023). https://doi.org/10.1007/s40520-023-02436-5

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  • DOI: https://doi.org/10.1007/s40520-023-02436-5

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