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. 2022 Aug 16;14(16):6449-6466.
doi: 10.18632/aging.204230. Epub 2022 Aug 16.

Fecal microbiota transplantation can improve cognition in patients with cognitive decline and Clostridioides difficile infection

Soo-Hyun Park  1 , Jung-Hwan Lee  2 , Jun-Seob Kim  3 , Tae Jung Kim  4 , Jongbeom Shin  5 , Jae Hyoung Im  6 , Boram Cha  5 , Suhjoon Lee  5 , Kye Sook Kwon  5 , Yong Woon Shin  5 , Sang-Bae Ko  4 , Seong Hye Choi  7
Affiliations

Fecal microbiota transplantation can improve cognition in patients with cognitive decline and Clostridioides difficile infection

Soo-Hyun Park et al. Aging (Albany NY). .

Abstract

After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although the gut microbiome has been associated with cognitive function, it remains to be elucidated whether fecal microbiota transplantation can improve cognition in patients with cognitive decline. The study included 10 patients (age range, 63-90 years; female, 80%) with dementia and severe CDI who were receiving FMT. Also, 10 patients (age range, 62-91; female, 80%) with dementia and severe CDI who were not receiving FMT. They were evaluated using cognitive function tests (Mini-Mental State Examination [MMSE] and Clinical Dementia Rating scale Sum of Boxes [CDR-SB]) at 1 month before and after FMT or antibiotics treatment (control group). The patients' fecal samples were analyzed to compare the composition of their gut microbiota before and 3 weeks after FMT or antibiotics treatment. Ten patients receiving FMT showed significantly improvements in clinical symptoms and cognitive functions compared to control group. The MMSE and CDR-SB of FMT group were improved compare to antibiotics treatment (MMSE: 16.00, median, 13.00-18.00 [IQR] vs. 10.0, median, 9.8-15.3 [IQR]); CDR-SB: 5.50, median, 4.00-8.00 [IQR]) vs. 8.0, median, 7.9-12.5, [IQR]). FMT led to changes in the recipient's gut microbiota composition, with enrichment of Proteobacteria and Bacteroidetes. Alanine, aspartate, and glutamate metabolism pathways were also significantly different after FMT. This study revealed important interactions between the gut microbiome and cognitive function. Moreover, it suggested that FMT may effectively delay cognitive decline in patients with dementia.

Keywords: Alzheimer’s dementia; brain-gut-axis; cognitive function; fecal microbiota transplantation; gut microbiome.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Figure 1
Figure 1
Mini-mental state examination (MMSE) and clinical dementia rating scale sum of boxes (CDR-SB) scores in the study groups. (A) Difference in the MMSE and CDR-SB scores before and after FMT. (B) Difference in the MMSE and CDR-SB scores before and after CDI. **P < 0.05, ***P > 0.05.
Figure 2
Figure 2
FMT alter the gut microbiome composition in dementia patients with severe Clostridioides difficile infection (CDI). (A) Phylum diversity pre- and post-FMT. (B) Genus diversity pre- and post-FMT. (C) Phylum diversity post-FMT and after antibiotics treatment. (D) Genus diversity post-FMT and after antibiotics treatment. *P > 0.05, **P < 0.05.
Figure 3
Figure 3
Microbiome analysis before and after fecal microbiota transplantation (FMT). (A) Alpha diversity was calculated using the number of overserved Chao and Shannon. (B) Principal coordinate analysis (PCoA) profile of microbial diversity across all samples using unweighted and weighted UniFrac. (C) Linear discriminant analysis effect size analysis (P < 0.05). *P > 0.05, **P < 0.05.
Figure 4
Figure 4
Microbiome analysis before antibiotics treatment and after antibiotics treatment. (A) Alpha diversity was calculated using the number of overserved Chao and Shannon. (B) Principal coordinate analysis (PCoA) profile of microbial diversity across all samples using unweighted and weighted UniFrac. (C) Linear discriminant analysis effect size analysis (P < 0.05). *P > 0.05.
Figure 5
Figure 5
Functional composition difference pre- and post-fecal microbiota transplantation (FMT). Relative abundances of the most abundant microbial pathways among the different groups. Data shown are the means ± SD. *P < 0.05.
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