Gut Microbiome Compositional and Functional Features Associate with Alzheimer's Disease Pathology.

Kang, Jea Woo; Khatib, Lora A; Heston, Margo B; Dilmore, Amanda H; Labus, Jennifer S; Deming, Yuetiva; Schimmel, Leyla; Blach, Colette; McDonald, Daniel; Gonzalez, Antonio; Bryant, MacKenzie; Sanders, Karenina; Schwartz, Ara; Ulland, Tyler K; Johnson, Sterling C; Asthana, Sanjay; Carlsson, Cynthia M; Chin, Nathaniel A; Blennow, Kaj; Zetterberg, Henrik; Rey, Federico E; Kaddurah-Daouk, Rima; Knight, Rob; Bendlin, Barbara B

Kang, Jea Woo; Khatib, Lora A; Heston, Margo B; Dilmore, Amanda H; Labus, Jennifer S; Deming, Yuetiva; Schimmel, Leyla; Blach, Colette; McDonald, Daniel; Gonzalez, Antonio; Bryant, MacKenzie; Sanders, Karenina; Schwartz, Ara; Ulland, Tyler K; Johnson, Sterling C; Asthana, Sanjay; Carlsson, Cynthia M; Chin, Nathaniel A; Blennow, Kaj; Zetterberg, Henrik; Rey, Federico E; Kaddurah-Daouk, Rima; Knight, Rob; Bendlin, Barbara B.

Afiliación

Kang JW; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Address: 600 Highland Ave, J5/1 Mezzanine, Madison, WI, USA 53792.
Khatib LA; Department of Pediatrics, University of California San Diego, La Jolla, California, USA Address: 9461 Gilman Dr, La Jolla, CA, USA 92093.
Heston MB; Neurosciences Graduate Program, University of California San Diego, La Jolla, California, USA Address: 9500 Gilman Dr, La Jolla, CA, USA 92093.
Dilmore AH; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Address: 600 Highland Ave, J5/1 Mezzanine, Madison, WI, USA 53792.
Labus JS; Department of Pediatrics, University of California San Diego, La Jolla, California, USA Address: 9461 Gilman Dr, La Jolla, CA, USA 92093.
Deming Y; Integrative Biostatistics and Bioinformatics Core (IBBC) at the Goodman-Luskin Microbiome Center Address: 42-210 CHS, Los Angeles, CA, USA 90095.
Schimmel L; G. Oppenheimer Center for Neurobiology of Stress and Resilience Address: 10833 Le Conte Ave, Los Angeles, CA, USA 90095.
Blach C; UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA Address: 100 Medical Plaza, Los Angeles, CA, USA 90095.
McDonald D; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Address: 600 Highland Ave, J5/1 Mezzanine, Madison, WI, USA 53792.
Gonzalez A; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA Address: 905 W Main St, Durham, NC, USA 27701.
Bryant M; Duke Molecular Physiology Institute, Duke University, Durham, NC, USA Address: 300 N Duke St, Durham, NC, USA 27701.
Sanders K; Department of Pediatrics, University of California San Diego, La Jolla, California, USA Address: 9461 Gilman Dr, La Jolla, CA, USA 92093.
Schwartz A; Department of Pediatrics, University of California San Diego, La Jolla, California, USA Address: 9461 Gilman Dr, La Jolla, CA, USA 92093.
Ulland TK; Department of Pediatrics, University of California San Diego, La Jolla, California, USA Address: 9461 Gilman Dr, La Jolla, CA, USA 92093.
Johnson SC; Department of Pediatrics, University of California San Diego, La Jolla, California, USA Address: 9461 Gilman Dr, La Jolla, CA, USA 92093.
Asthana S; Department of Pediatrics, University of California San Diego, La Jolla, California, USA Address: 9461 Gilman Dr, La Jolla, CA, USA 92093.
Carlsson CM; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Address: 600 Highland Ave, J5/1 Mezzanine, Madison, WI, USA 53792.
Chin NA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA Address: 1685 Highland Ave, Madison, WI, USA 53705.
Blennow K; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Address: 600 Highland Ave, J5/1 Mezzanine, Madison, WI, USA 53792.
Zetterberg H; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Address: 600 Highland Ave, J5/1 Mezzanine, Madison, WI, USA 53792.
Rey FE; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Address: 600 Highland Ave, J5/1 Mezzanine, Madison, WI, USA 53792.
Kaddurah-Daouk R; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden Address: Blå stråket 15, vån 3 SU/Sahlgrenska 413 45 Göteborg, Sweden.
Knight R; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden Address: Blå stråket 15, vån 3 SU/Sahlgrenska 413 45 Göteborg, Sweden.
Bendlin BB; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden Address: Blå stråket 5, 413 45 Göteborg, Sweden.

medRxiv ; 2024 Sep 05.

Article en En | MEDLINE | ID: mdl-39281749

ABSTRACT

ABSTRACT

BACKGROUND:

The gut microbiome is a potentially modifiable factor in Alzheimer's disease (AD); however, understanding of its composition and function regarding AD pathology is limited.

METHODS:

Shallow-shotgun metagenomic data was used to analyze fecal microbiome from participants enrolled in the Wisconsin Microbiome in Alzheimer's Risk Study, leveraging clinical data and cerebrospinal fluid (CSF) biomarkers. Differential abundance and ordinary least squares regression analyses were performed to find differentially abundant gut microbiome features and their associations with CSF biomarkers of AD and related pathologies.

RESULTS:

Gut microbiome composition and function differed between people with AD and cognitively unimpaired individuals. The compositional difference was replicated in an independent cohort. Differentially abundant gut microbiome features were associated with CSF biomarkers of AD and related pathologies.

DISCUSSION:

These findings enhance our understanding of alterations in gut microbial composition and function in AD, and suggest that gut microbes and their pathways are linked to AD pathology.

Palabras clave

Alzheimer's disease; Biomarkers; Cerebrospinal fluid; Composition; Differential abundance; Function; Gut microbiome; Pathology

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