Pilot study of autologous fecal microbiota transplants in nursing home residents: Feasibility and safety

Christine K Liu, Janet Seo, Vassiliki Pravodelov, Susan Frazier, Marsha Guy, Katherine Concilio, Rossana Lau-Ng, Gary Brandeis, Jon Watson, Jeannette van der Velde, Scott W Olesen, Shrish Budree, Mary Njenga, Zain Kassam, Majdi Osman, Christine K Liu, Janet Seo, Vassiliki Pravodelov, Susan Frazier, Marsha Guy, Katherine Concilio, Rossana Lau-Ng, Gary Brandeis, Jon Watson, Jeannette van der Velde, Scott W Olesen, Shrish Budree, Mary Njenga, Zain Kassam, Majdi Osman

Abstract

Introduction: Antibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population.

Methods: Pilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE).

Results: We screened 468 nursing home residents aged ≥18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2 ± 8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention.

Conclusions: In this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe.

Trial registration: ClinicalTrials.gov Identifier: NCT03061097.

Keywords: AE, adverse event; ARBI, antibiotic resistant bacterial infections; Elderly; FMT, fecal microbiota transplant; Fecal transplants; Microbiota; Nursing home; Older adults; SAE, serious adverse event; aFMT, autologous fecal microbiota transplant.

Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shrish Budree is a shareholder and employee of Finch Therapeutics. Zain Kassam is a shareholder of Finch Therapeutics.

Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
CONSORT diagram of study.

References

    1. Pamer E.G. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science. 2016;352:535–538. doi: 10.1126/science.aad9382. 80.
    1. Kelly C.R., Yen E.F., Grinspan A.M., Kahn S.A., Atreja A., Lewis J.D., et al. Fecal microbiota transplantation is highly effective in real-world practice: initial results from the FMT national registry. Gastroenterology. 2021;160:183–192. doi: 10.1053/j.gastro.2020.09.038. e3.
    1. Relman D.A. The human microbiome: ecosystem resilience and health. Nutr. Rev. 2012;70 doi: 10.1111/j.1753-4887.2012.00489.x.
    1. Becattini S., Taur Y., Pamer E.G. Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol. Med. 2016;22:458–478. doi: 10.1016/j.molmed.2016.04.003.
    1. Hentges D.J., Freter R. In vivo and in vitro antagonism of intestinal bacteria against shigella flexneri i. correlation between various tests. J. Infect. Dis. 1962;110:30–37. doi: 10.1093/infdis/110.1.30.
    1. Freter R. In vivo and in vitro antagonism of intestinal bacteria against shigella flexneri ii. the inhibitory mechanism. J. Infect. Dis. 1962;110:38–46. doi: 10.1093/infdis/110.1.38.
    1. Bohnhoff M., Miller C.P. Enhanced susceptibility to salmonella infection in streptomycin-treated mice. J. Infect. Dis. 1962;111:117–127. doi: 10.1093/infdis/111.2.117.
    1. Basson A.R., Zhou Y., Seo B., Rodriguez-Palacios A., Cominelli F. Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease. Transl. Res. 2020;226:1–11. doi: 10.1016/j.trsl.2020.05.008.
    1. Taur Y., Coyte K., Schluter J., Robilotti E., Figueroa C., Gjonbalaj M., et al. Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant. Sci. Transl. Med. 2018;10 doi: 10.1126/scitranslmed.aap9489.
    1. Centers for Disease Control and Prevention . 2017. The Core Elements of Antibiotic Stewardship for Nursing Homes CDC; pp. 1–21.
    1. Chen J., Zaman A., Ramakrishna B., Olesen S.W. Stool Banking for fecal microbiota transplantation: methods and operations at a large stool bank. Front. Cell Infect. Microbiol. 2021;11 doi: 10.3389/fcimb.2021.622949.
    1. Bolyen E., Rideout J.R., Dillon M.R., Bokulich N.A., Abnet C.C., Al-Ghalith G.A., et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 2019;37:852–857. doi: 10.1038/s41587-019-0209-9.
    1. Amir A., McDonald D., Navas-Molina J.A., Kopylova E., Morton J.T., Zech Xu Z., et al. Deblur rapidly resolves single-nucleotide community sequence patterns. mSystems. 2017;2:191–207. doi: 10.1128/msystems.00191-16.
    1. Wang Q., Garrity G.M., Tiedje J.M., Cole J.R. Naïve Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 2007;73:5261–5267. doi: 10.1128/AEM.00062-07.
    1. DeSantis T.Z., Hugenholtz P., Larsen N., Rojas M., Brodie E.L., Keller K., et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 2006;72:5069–5072. doi: 10.1128/AEM.03006-05.
    1. Claesson M.J., Cusack S., O'Sullivan O., Greene-Diniz R., De Weerd H., Flannery E., et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc. Natl. Acad. Sci. U. S. A. 2011;108:4586–4591. doi: 10.1073/pnas.1000097107.
    1. Odamaki T., Kato K., Sugahara H., Hashikura N., Takahashi S., Xiao J.Z., et al. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 2016;16:90. doi: 10.1186/s12866-016-0708-5.
    1. Kong F., Deng F., Li Y., Zhao J. Identification of gut microbiome signatures associated with longevity provides a promising modulation target for healthy aging. Gut Microb. 2019;10:210–215. doi: 10.1080/19490976.2018.1494102.
    1. Suez J., Zmora N., Zilberman-Schapira G., Mor U., Dori-Bachash M., Bashiardes S., et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018;174:1406–1423. doi: 10.1016/j.cell.2018.08.047. e16.
    1. Bulow C., Langdon A., Hink T., Wallace M., Reske K.A., Patel S., et al. Impact of amoxicillin-clavulanate followed by autologous fecal microbiota transplantation on fecal microbiome structure and metabolic potential. mSphere. 2018;3:588–606. doi: 10.1128/mspheredirect.00588-18.
    1. Rao S., Go J. Update on the management of constipation in the elderly: new treatment options. Clin. Interv. Aging. 2010;5:417–418. doi: 10.2147/cia.s14548.
    1. Fosnes G.S., Lydersen S., Farup P.G. Drugs and constipation in elderly in nursing homes: what is the relation? Gastroenterol. Res. Pract. 2012;2012 doi: 10.1155/2012/290231.
    1. Mitchell S.L. Advanced dementia. N. Engl. J. Med. 2015;372:2533–2540. doi: 10.1056/nejmcp1412652.
    1. Center for Health Statistics N . 2015. Vital and health statistics, Series 3, Number 43.
    1. Wang S., Xu M., Wang W., Cao X., Piao M., Khan S., et al. Systematic review: adverse events of fecal Microbiota transplantation. PLoS One. 2016;11 doi: 10.1371/journal.pone.0161174.
    1. Agrawal M., Aroniadis O.C., Brandt L.J., Kelly C., Freeman S., Surawicz C., et al. The long-term efficacy and safety of fecal microbiota transplant for recurrent, severe, and complicated clostridium difficile infection in 146 elderly individuals. J. Clin. Gastroenterol. 2016;50:403–407. doi: 10.1097/MCG.0000000000000410.
    1. Luo Y., Tixier E.N., Grinspan A.M. Fecal microbiota transplantation for Clostridioides difficile in high-risk older adults is associated with early recurrence. Dig. Dis. Sci. 2020;65:3647–3651. doi: 10.1007/s10620-020-06147-z.
    1. Li S., Middleton A., Ottenbacher K.J., Goodwin J.S. Original Study: trajectories over the first year of long-term care nursing home residence HHS Public Access. J. Am. Med. Dir. Assoc. 2018;19:333–341. doi: 10.1016/j.jamda.2017.09.021.
    1. Gambassi G., Landi F., Lapane K.L., Sgadari A., Mor V., Bernabei R. Predictors of mortality in patients with Alzheimer's disease living in nursing homes. J. Neurol. Neurosurg. Psychiatry. 1999;67:59–65. doi: 10.1136/jnnp.67.1.59.
    1. Grabowski D.C., O'Malley A.J., Barhydt N.R. The costs and potential savings associated with nursing home hospitalizations. Health Aff. 2007;26:1753–1761. doi: 10.1377/hlthaff.26.6.1753.
    1. Petrof E.O., Khoruts A. From stool transplants to next-generation microbiota therapeutics. Gastroenterology. 2014;146:1573–1582. doi: 10.1053/j.gastro.2014.01.004.
    1. Gerardin Y., Timberlake S., Allegretti J.R., Smith M.B., Kassam Z. Beyond fecal microbiota transplantation: developing drugs from the microbiome. J. Infect. Dis. 2020 doi: 10.1093/infdis/jiaa700.
    1. Services U . Centers Dis Control Prev; 2019. D of H and H. Antibiotic Resistance Threats in the United States; pp. 1–113.
    1. Bothwell L.E., Greene J.A., Podolsky S.H., Jones D.S. Assessing the gold standard — lessons from the history of RCTs. N. Engl. J. Med. 2016;374:2175–2181. doi: 10.1056/nejmms1604593.
    1. Coman V., Vodnar D.C. Gut microbiota and old age: modulating factors and interventions for healthy longevity. Exp. Gerontol. 2020;141 doi: 10.1016/j.exger.2020.111095.

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