Evidence map›Paper›PMID 38329121›Full record

ArticleJCI insight2024

Abnormalities in microbiota/butyrate/FFAR3 signaling in aging gut impair brain function.

Sidharth P Mishra, Shalini Jain, Bo Wang, Shaohua Wang, Brandi C Miller, Jea Y Lee, Cesar V Borlongan, Lin Jiang, Julie Pollak, Subhash Taraphder and 3 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
12.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Effects ofFrontiers in nutrition · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 2 countries.

Sidharth P MishraUSF Center for Microbiome Research.
Shalini JainUSF Center for Microbiome Research.
Bo WangDepartment of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, Florida, USA.
Shaohua WangUSF Center for Microbiome Research.
Brandi C MillerUSF Center for Microbiome Research.
Jea Y LeeDepartment of Neurosurgery and Brain Repair, and.
Cesar V BorlonganDepartment of Neurosurgery and Brain Repair, and.
Lin JiangNatural Sciences Division, New College of Florida, Sarasota, Florida, USA.
Julie PollakDepartment of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, Florida, USA.
Subhash TaraphderDepartment of Animal Genetics and Breeding, West Bengal University of Animal & Fishery Sciences, Kolkata, India.
Brian T LaydenDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
Sushil G RaneDiabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA.
Hariom YadavUSF Center for Microbiome Research.
Altair Engineering (United States) · USFlorida Institute of Technology · USNational Institute of Diabetes and Digestive and Kidney Diseases · USNew College of Florida · USUniversity of Illinois Chicago · USWest Bengal University of Animal and Fishery Sciences · IN

Funding

Cell Cycle Regulators in Diabetes and ObesityZIADK055107 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI RANE, SUSHIL · 2009 to 2025
$8.4M
Transforming Growth Factor Beta Superfamily Signaling in Pancreas BiologyZIADK075073 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI RANE, SUSHIL · 2012 to 2025
$7.0M
Repurposing of Metormin for Older Patients with HFpEFU01AG076928 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI KITZMAN, DALANE W, YADAV, HARIOM · 2022 to 2024
$2.3M
Gut microbiota-based biomarkers of Alzheimer's disease and its modulation by a ketogenic dietR56AG064075 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI YADAV, HARIOM · 2020 to 2021
$1.2M
Microbial therapy improves gut permeability to reduce cognitive decline and Alzheimer’s diseaseRF1AG071762 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI YADAV, HARIOM · 2021 to 2021
$1.1M
Microbial therapy improves gut permeability to reduce cognitive decline and Alzheimer’s diseaseR01AG071762 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI YADAV, HARIOM · 2024 to 2025
$753k
The role of gut microbiota in the efficacy of ketogenic diet to ameliorate Alzheimer's diseaseR21AG072379 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI YADAV, HARIOM · 2021 to 2021
$429k
Identification of bacterial strains for development of an oral probiotic aimed at increasing nitric oxide bioavailabilityR21DE032197 · NIDCR · WAKE FOREST UNIVERSITY · PI KIM-SHAPIRO, DANIEL B, YADAV, HARIOM · 2023 to 2024
$422k
Metformin and Alzheimer's disease: Underlying Mechanisms that Ameliorate ProgressionR56AG069676 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI YADAV, HARIOM · 2020 to 2020
$388k
NIA NIH HHS R01 AG071762NIA NIH HHS R21 AG072379NIA NIH HHS R56 AG064075NIA NIH HHS R56 AG069676NIA NIH HHS RF1 AG071762NIA NIH HHS U01 AG076928NIDCR NIH HHS R21 DE032197
6 · The paper itself

Abstract

Aging-related abnormalities in gut microbiota are associated with cognitive decline, depression, and anxiety, but underlying mechanisms remain unstudied. Here, our study demonstrated that transplanting old gut microbiota to young mice induced inflammation in the gut and brain coupled with cognitive decline, depression, and anxiety. We observed diminished mucin formation and increased gut permeability ("leaky gut") with a reduction in beneficial metabolites like butyrate because of decline in butyrate-producing bacteria in the aged gut microbiota. This led to suppressed expression of butyrate receptors, free fatty acid receptors 2 and 3 (FFAR2/3). Administering butyrate alleviated inflammation, restored mucin expression and gut barriers, and corrected brain dysfunction. Furthermore, young mice with intestine-specific loss of FFAR2/3 exhibited gut and brain abnormalities akin to those in older mice. Our results demonstrate that reduced butyrate-producing bacteria in aged gut microbiota result in low butyrate levels and reduced FFAR2/3 signaling, leading to suppressed mucin formation that increases gut permeability, inflammation, and brain abnormalities. These findings underscore the significance of butyrate-FFAR2/3 agonism as a potential strategy to mitigate aged gut microbiota-induced detrimental effects on gut and brain health in older adults.

Indexed as

ButyratesGastrointestinal MicrobiomeAgingAnimalsBrainInflammationMiceMucinsReceptors, G-Protein-CoupledButyratesFFAR3 protein, mouseMucinsReceptors, G-Protein-CoupledAgingAlzheimer diseaseBioinformaticsG protein–coupled receptorsMicrobiology

Identifiers

PMID38329121
PMCPMC10967378
OpenAlexW4394739110

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.