Fungi in Gut Linked to Higher Alzheimer’s Risk Can Be Reduced Through Ketogenic Diet

Summary: Following the Mediterranean ketogenic diet can help modulate unique fungi found in the gut of those with mild cognitive impairment.

Source: Wake Forest Baptist Medical Center

Specific fungi in the gut associated with a higher risk of Alzheimer’s disease and found in people with mild cognitive impairment (MCI) can be altered in a beneficial manner by eating a modified Mediterranean diet, researchers at Wake Forest School of Medicine have found.

The small study is published in the current online edition of the journal EBioMedicine.

“Our study reveals that unique fungi co-living with bacteria in the gut of patients with MCI can be modulated through a Mediterranean ketogenic diet,” said principal investigator Hariom Yadav, assistant professor of molecular medicine at Wake Forest School of Medicine, part of Wake Forest Baptist Health.

In the single-center, randomized, double-blind crossover pilot study, Yadav’s team identified the organisms in the gut microbiome by sequencing the fungal rRNA ITS1 gene in 17 older adults (11 with diagnosed MCI and six with normal cognition) before and after a six-week intervention of a modified Mediterranean ketogenic diet or the American Heart Association Diet to determine its correlation with Alzheimer’s markers in cerebrospinal fluid and gut bacteria.

“Our study reveals that unique fungi co-living with bacteria in the gut of patients with MCI can be modulated through a Mediterranean ketogenic diet,” said principal investigator Hariom Yadav. Image is credited to Wake Forest Baptist Medical Center.

“Although we do not fully understand how these fungi contribute to Alzheimer’s disease, this is the first study of its kind to reveal their role in our mental health, which we hope will ignite thinking in the scientific community to develop better understanding of them in relation to Alzheimer’s disease,” Yadav said. “It also indicates that dietary habits such as eating a ketogenic diet can reduce harmful fungi in the gut which might help in reducing Alzheimer’s disease processes in the brain.”

Funding: The work was supported by the National Institutes of Health, P30AG049638, R01AG055122, and R01AG018915; the Pepper Older Americans for Independence Center, P30AG21332; and the Department of Defense, W81XWH-19-1-0236.

About this Alzheimer’s disease research article

Source:
Wake Forest Baptist Medical Center
Contacts:
Marguerite Beck – Wake Forest Baptist Medical Center
Image Source:
The image is credited to Wake Forest Baptist Medical Center.

Original Research: Open access
“Gut mycobiome and its interaction with diet, gut bacteria and alzheimer’s disease markers in subjects with mild cognitive impairment: A pilot study” by Hariom Yadav et al. EBioMedicine.


Abstract

Gut mycobiome and its interaction with diet, gut bacteria and alzheimer’s disease markers in subjects with mild cognitive impairment: A pilot study

Background
Recently, we reported that patients with mild cognitive impairment (MCI) harbor specific signature of bacteria in their gut and that a modified Mediterranean ketogenic diet (MMKD) improves Alzheimer’s disease (AD) markers in cerebrospinal fluid (CSF) and the signatures of gut bacteria. However, other microbial population such as gut fungi (mycobiome) in relation to MCI/AD pathology, gut bacteria and diet remain unknown.

Methods
We measure gut mycobiome by sequencing of the fungal rRNA ITS1 gene in 17 older adults (11 MCI; 6 cognitively normal [CN]) in a single-center, randomized, double-blind, crossover pilot study, before and after 6 weeks intervention of MMKD and American Heart Association Diet (AHAD), and determine its correlation with AD markers in CSF and gut bacteria.

Findings
Compared to CN counterparts, patients with MCI have higher proportion of families Sclerotiniaceae, Phaffomyceteceae, Trichocomaceae, Cystofilobasidiaceae, Togniniaceae and genera Botrytis, Kazachstania, Phaeoacremonium and Cladosporium and lower abundance of Meyerozyma. Specific fungal taxa exhibit distinct correlation arrays with AD markers and gut bacteria in subjects with versus without MCI. MMKD induces broader effect on fungal diversity in subjects with MCI and increases Agaricus and Mrakia while decreasing Saccharomyces and Claviceps with differential response in subjects with or without MCI.

Interpretation
The study reveals MCI-specific mycobiome signatures and demonstrates that distinct diets modulate the mycobiome in association with AD markers and fungal-bacterial co-regulation networks in patients with MCI. The findings corroborate the notion of considering gut mycobiome as a unique factor that can affect cognitive health/AD by interacting with gut bacteria and diet and facilitate better understanding of the AD and related microbiome, using unique diet or microbiome modulators.

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