Assessment of the Gut Microbiome in Patients with Coexisting Irritable Bowel Syndrome and Chronic Fatigue Syndrome, 2025, Chojnacki

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Assessment of the Gut Microbiome in Patients with Coexisting Irritable Bowel Syndrome and Chronic Fatigue Syndrome​

by
Marcin Chojnacki
1,
Aleksandra Błońska
1,
Aleksandra Kaczka
1,
Jan Chojnacki
1,
Ewa Walecka-Kapica
2,
Natalia Romanowska
2,
Karolina Przybylowska-Sygut
3and
Tomasz Popławski
3,*



1
Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland
2
Department of Gastroenterology, Medical University of Lodz, 92-213 Lodz, Poland
3
Department of Pharmaceutical Microbiology and Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland
*
Author to whom correspondence should be addressed.
Nutrients 2025, 17(13), 2232; https://doi.org/10.3390/nu17132232
Submission received: 21 May 2025 / Revised: 30 June 2025 / Accepted: 2 July 2025 / Published: 5 July 2025
(This article belongs to the Special Issue Exploring the Evaluation and Treatment of Extraintestinal Disease Symptoms in Patients with Gut Dysbiosis)

Versions Notes


Abstract​

Background:
The gut microbiome is a key modulator of the gut–brain axis and may contribute to the pathophysiology of both gastrointestinal and systemic disorders. This study aimed to evaluate gut microbiota composition and tryptophan/phenylalanine metabolism in women with unclassified irritable bowel syndrome (IBS-U), with or without coexisting chronic fatigue syndrome (CFS).

Methods:
Eighty women were enrolled and divided into two groups: IBS-U without CFS (Group I, n = 40) and IBS-U with coexisting CFS (Group II, n = 40). Microbial composition and diversity were assessed using the GA-map™ Dysbiosis Test, including the dysbiosis index (DI) and Shannon Diversity Index (SDI). Hydrogen and methane levels were measured in breath samples. Urinary concentrations of selected microbial and neuroactive metabolites—homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), xanthurenic acid (XA), quinolinic acid (QA), hydroxyphenylacetic acid (HPA), and 3-indoxyl sulfate (3-IS)—were quantified using LC-MS/MS. Fatigue severity was assessed using the Chalder Fatigue Questionnaire (CFQ-11) and the fatigue severity scale (FSS).

Results:
Compared to Group I, patients with IBS-CFS showed significantly greater microbial diversity, higher breath methane levels, and elevated urinary concentrations of QA, XA, 3-IS, and HVA, alongside lower concentrations of 5-HIAA and KYN. Fatigue severity was positively correlated with urinary XA and QA levels.

Conclusions:
Women with IBS and coexisting CFS exhibit distinct gut microbiota and tryptophan metabolite profiles compared to those without fatigue. The observed metabolite–symptom associations, particularly involving neuroactive kynurenine derivatives, warrant further investigation. These preliminary findings should be interpreted as hypothesis-generating and require validation through high-resolution microbiome analyses, functional pathway profiling, and longitudinal or interventional studies to clarify causality and clinical significance.

Keywords:
irritable bowel syndrome; chronic fatigue syndrome; gut microbiome; tryptophan metabolism; kynurenine pathway; LC-MS/MS

 
elevated urinary concentrations of QA, XA, 3-IS, and HVA

Quinolinic acid (QA) is an NMDA receptor agonist, potentially neurotoxic, produced by microglia and macrophages in the brain during inflammation
Xanthurenic acid (XA) is primarily produced in the brain, specifically within neurons

... do these 2 metabolites ring any bells? (I am too inexpert to know)
 
Quinolinic acid (QA) is an NMDA receptor agonist, potentially neurotoxic, produced by microglia and macrophages in the brain during inflammation
Xanthurenic acid (XA) is primarily produced in the brain, specifically within neurons

... do these 2 metabolites ring any bells? (I am too inexpert to know)

Both of these have been implicated in ME/CFS before and are kynurenine pathway metabolites.
 
That these 2 metabolites come from brain cells lend support to any hypotheses/studies? Gut-Vagus nerve connections? Brain inflammation studies? T-cell activation or trafficking?

Does their presence lend support to Robert Phair's efforts?
 
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