Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments

BackgroundRecent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown.ObjectivesThis study aimed to inves...

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Main Authors: Xiaoxia Chen, Wanling Zhang, Zhijun Lin, Chunyan Zheng, Shufang Chen, Haihong Zhou, Zhou Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2023.1103189/full
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author Xiaoxia Chen
Wanling Zhang
Zhijun Lin
Chunyan Zheng
Shufang Chen
Haihong Zhou
Zhou Liu
author_facet Xiaoxia Chen
Wanling Zhang
Zhijun Lin
Chunyan Zheng
Shufang Chen
Haihong Zhou
Zhou Liu
author_sort Xiaoxia Chen
collection DOAJ
description BackgroundRecent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown.ObjectivesThis study aimed to investigate the safety and efficacy of FMT for cognitive impairment treatment.MethodsFive patients aged 54–80 years (three women) were enrolled in this single-arm clinical trial from July 2021 to May 2022. The Montreal Cognitive Assessment-B (MoCA-B), Activities of Daily Living (ADL), and the cognitive section of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) were assessed at days 0, 30, 60, 90, and 180. Additionally, stool and serum samples were obtained twice before FMT was administered and six months after the treatment. The structure of fecal microbiota was analyzed by 16S RNA gene sequencing. Serum samples were analyzed for metabolomics and lipopolysaccharide (LPS)-binding proteins by liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Safety was assessed based on adverse events, vital signs, and laboratory parameters during FMT and the follow-up period.ResultsThe MoCA, ADL, and ADAS-Cog scores of patients with mild cognitive impairment (patients C and E) after FMT were improved or maintained compared with those before transplantation. However, patients with severe cognitive impairment (patients A, B, and D) had no worsening of cognitive scores. Fecal microbiota analysis showed that FMT changed the structure of gut microbiota. The results of serum metabolomics analysis suggested that there were significant changes in the serum metabolomics of patients after FMT, with 7 up-regulated and 28 down-regulated metabolites. 3b,12a-dihydroxy-5a-cholanoic acid, 25-acetylvulgaroside, deoxycholic acid, 2(R)-hydroxydocosanoic acid, and P-anisic acid increased, while bilirubin and other metabolites decreased. KEFF pathway analysis indicated that the main metabolic pathways were bile secretion and choline metabolism in cancer. No adverse effects were reported throughout the study.ConclusionsIn this pilot study, FMT could maintain and improve cognitive function in mild cognitive impairment by changing gut microbiota structure and affecting serum metabolomics. Fecal bacteria capsules were safe. However, further studies are needed to evaluate the safety and efficacy of fecal microbiota transplantation. ClinicalTrials.gov Identifier: CHiCTR2100043548.
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spelling doaj.art-c3c2a944d7dc41f99154363ddfce44ac2023-04-11T10:01:25ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-04-011310.3389/fcimb.2023.11031891103189Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairmentsXiaoxia ChenWanling ZhangZhijun LinChunyan ZhengShufang ChenHaihong ZhouZhou LiuBackgroundRecent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown.ObjectivesThis study aimed to investigate the safety and efficacy of FMT for cognitive impairment treatment.MethodsFive patients aged 54–80 years (three women) were enrolled in this single-arm clinical trial from July 2021 to May 2022. The Montreal Cognitive Assessment-B (MoCA-B), Activities of Daily Living (ADL), and the cognitive section of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) were assessed at days 0, 30, 60, 90, and 180. Additionally, stool and serum samples were obtained twice before FMT was administered and six months after the treatment. The structure of fecal microbiota was analyzed by 16S RNA gene sequencing. Serum samples were analyzed for metabolomics and lipopolysaccharide (LPS)-binding proteins by liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Safety was assessed based on adverse events, vital signs, and laboratory parameters during FMT and the follow-up period.ResultsThe MoCA, ADL, and ADAS-Cog scores of patients with mild cognitive impairment (patients C and E) after FMT were improved or maintained compared with those before transplantation. However, patients with severe cognitive impairment (patients A, B, and D) had no worsening of cognitive scores. Fecal microbiota analysis showed that FMT changed the structure of gut microbiota. The results of serum metabolomics analysis suggested that there were significant changes in the serum metabolomics of patients after FMT, with 7 up-regulated and 28 down-regulated metabolites. 3b,12a-dihydroxy-5a-cholanoic acid, 25-acetylvulgaroside, deoxycholic acid, 2(R)-hydroxydocosanoic acid, and P-anisic acid increased, while bilirubin and other metabolites decreased. KEFF pathway analysis indicated that the main metabolic pathways were bile secretion and choline metabolism in cancer. No adverse effects were reported throughout the study.ConclusionsIn this pilot study, FMT could maintain and improve cognitive function in mild cognitive impairment by changing gut microbiota structure and affecting serum metabolomics. Fecal bacteria capsules were safe. However, further studies are needed to evaluate the safety and efficacy of fecal microbiota transplantation. ClinicalTrials.gov Identifier: CHiCTR2100043548.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1103189/fullfecal microbiota transplantationcognitive disordergut microbiotametabolomicssafety
spellingShingle Xiaoxia Chen
Wanling Zhang
Zhijun Lin
Chunyan Zheng
Shufang Chen
Haihong Zhou
Zhou Liu
Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments
Frontiers in Cellular and Infection Microbiology
fecal microbiota transplantation
cognitive disorder
gut microbiota
metabolomics
safety
title Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments
title_full Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments
title_fullStr Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments
title_full_unstemmed Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments
title_short Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments
title_sort preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments
topic fecal microbiota transplantation
cognitive disorder
gut microbiota
metabolomics
safety
url https://www.frontiersin.org/articles/10.3389/fcimb.2023.1103189/full
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