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Record W4414320930 · doi:10.1101/2025.09.15.25335180

Altered microbial carbohydrate metabolism is associated with anxiety and gastrointestinal symptoms in patients with Generalized Anxiety Disorder

2025· preprint· en· W4414320930 on OpenAlexaff
Virginia Rabbia, Merwa Amer, Giada De Palma, Ryan Potts, Heather Armstrong, Stephen M. Collins, Michael T. Bailey, Michael G. Surette, Rebecca Anglin, Přemysl Berčík

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicDiet and metabolism studies
Canadian institutionsInstitute of Infection and ImmunityUniversity of ManitobaMcMaster University
Fundersnot available
KeywordsGeneralized anxiety disorderEtiologyIrritable bowel syndromeGut–brain axisBacteroidesGut floraImmune systemCarbohydrate

Abstract

fetched live from OpenAlex

Abstract Background Generalized anxiety disorder (GAD) is a common psychiatric condition, with unknown etiology and pathophysiology. Recent studies have suggested alterations in the microbiota-gut-brain axis may be involved in the development of GAD. We aimed to explore the interactions between the gut microbiota, gastrointestinal and psychiatric symptoms, neuroimmune markers and dietary patterns in patients with GAD. Methods We recruited 83 GAD patients and 98 age- and sex-matched healthy controls (HC) and assessed their psychiatric and gastrointestinal symptoms, and long-term diet using validated questionnaires. We measured serum and stool neuroimmune markers and metabolites by ELISA and LC-MS, microbiota was analyzed using 16S rRNA gene sequencing with functional predictions by PICRUSt2. Microbial carbohydrate degradation capacity was assessed ex vivo . The data was analyzed using classical statistics and machine learning (XGBoost). Results GAD patients exhibited higher BMI, gastrointestinal symptoms and inflammatory markers, while reporting reduced intake of fiber and other macro- and micronutrients compared to HC. Gastrointestinal symptoms were the most predictive feature separating GAD from HC. GAD patients had a distinct microbiota profile, dominated by Bacteroides , compared with a Prevotella -dominated microbiota in HC. Carbohydrate degradation pathways were enriched in GAD and strongly associated with Bacteroides abundance. Anxiety scores correlated with Bacteroides abundance, carbohydrate degradation pathways and gastrointestinal symptoms, while negatively correlating with dietary fiber intake. Ex vivo mucin-to-inulin degradation ratio was higher in GAD and correlated with inflammatory markers. Conclusions GAD patients exhibited marked gastrointestinal symptoms, elevated immune markers, reduced fiber intake and a Bacteroides -dominated microbiota that preferentially degrades mucin. These data suggest that their microbiota adapted to utilize host-derived carbohydrates that may affect the mucus barrier, altering immune homeostasis and leading to gastrointestinal symptoms and anxiety. Dietary interventions, such as gradually increasing fiber intake, could reprogram bacterial carbohydrate metabolism, thus ameliorating gut barrier function and alleviating anxiety and gastrointestinal symptoms.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.226
Teacher spread0.219 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2025
Admission routes1
Has abstractyes

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