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

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          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.

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          Metagenomic biomarker discovery and explanation

          This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
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            Search and clustering orders of magnitude faster than BLAST.

            Biological sequence data is accumulating rapidly, motivating the development of improved high-throughput methods for sequence classification. UBLAST and USEARCH are new algorithms enabling sensitive local and global search of large sequence databases at exceptionally high speeds. They are often orders of magnitude faster than BLAST in practical applications, though sensitivity to distant protein relationships is lower. UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters. UCLUST offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets. Binaries are available at no charge for non-commercial use at http://www.drive5.com/usearch.
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              Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences

              Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community’s functional capabilities. Here we describe PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this ‘predictive metagenomic’ approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                31 August 2022
                16 August 2022
                : 14
                : 16
                : 6449-6466
                Affiliations
                [1 ]Department of Neurology, Department of Critical Care Medicine, Department of Hospital Medicine, Inha University Hospital, Incheon 22332, Republic of Korea
                [2 ]Division of Gastroenterology, Department of Internal Medicine, Department of Hospital Medicine, Inha University Hospital, Incheon 22332, Republic of Korea
                [3 ]Department of Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
                [4 ]Department of Neurology and Department of Critical Care Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea
                [5 ]Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon 22332, Republic of Korea
                [6 ]Division of Infectious Diseases, Department of Internal Medicine, Inha University School of Medicine, Incheon 22332, Republic of Korea
                [7 ]Department of Neurology, Inha University School of Medicine, Incheon 22332, Republic of Korea
                Author notes
                Correspondence to: Seong Hye Choi; email: seonghye@inha.ac.kr
                Correspondence to: Kye Sook Kwon; email: kskwon@inha.ac.kr
                Article
                204230 204230
                10.18632/aging.204230
                9467396
                35980280
                5338247b-b489-44a1-9ed9-559b6078d046
                Copyright: © 2022 Park et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 February 2022
                : 04 August 2022
                Categories
                Research Paper

                Cell biology
                fecal microbiota transplantation,gut microbiome,brain-gut-axis,cognitive function,alzheimer’s dementia

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