# Abnormal Homeostasis in the Redox State and Related Signaling Pathways, in Irritable Bowel Syndrome

## TL;DR

This study finds that irritable bowel syndrome is linked to oxidative stress and inflammation, with differences in how these factors interact in different IBS subtypes.

## Contribution

The study identifies specific redox and inflammatory biomarker imbalances in IBS and their subtype-specific correlations.

## Key findings

- IBS patients show higher oxidative stress markers like MDA and GSSG, and lower antioxidant GSH compared to controls.
- IBS is associated with elevated NF-κB and reduced Nrf2, indicating disrupted redox homeostasis.
- IBS-D shows antioxidant mechanisms counteracting inflammation, while IBS-C shows interleukin-mediated anti-inflammatory effects.

## Abstract

IBS is multifactorial; however, elucidating its underlying mechanisms is crucial for advancing in its diagnosis and management.

Evaluate molecular processes related to oxidative stress (OS) and inflammation in IBS and its subtypes.

Thirty Rome III‐IBS outpatients and 30 controls were studied for OS biomarkers, including malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), and oxidized glutathione (GSSG). Also, serum interleukins (IL‐10, IL‐4, TNF‐α, IL‐6), and the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), nuclear factor erythroid 2‐related factor 2 (Nrf2), and nicotinamide‐adenine‐dinucleotide phosphate (NADPH) catalytic subunit gp91phox.

In IBS vs. controls there were higher MDA: 4.44 ± 1.76 vs. 2.42 ± 0.5 nmol/mg/protein (p < 0.01); GSSG: 57.17 ± 17.49 vs. 42.73 ± 14.26 μM (p < 0.01); and lower GSH: 26.17 ± 12.36 vs. 38.47 ± 16.71 μM (p < 0.01). Also, an imbalance in pro‐ and anti‐inflammatory interleukins (p < 0.01); and higher NF‐κB: 5.33 ± 3.39 vs. 3.08 ± 1.19 (p = 0.01); gp91phox: 4.28 ± 1.81 vs. 3.29 ± 1.03 (p < 0.05); and lower Nrf2: 3.87 ± 2.9 vs. 7.56 ± 2.59 (p < 0.05). Additionally, there were no significant differences between the IBS subtypes, nor according to severity. Finally, in IBS‐C, MDA correlated with IL‐4, TNF‐α with IL‐10; and in IBS‐D, GSH correlated with IL‐4 and no differences in transcription factors.

The data demonstrate an alteration in the homeostasis of the cellular redox state in IBS. Also, in IBS‐D, the antioxidant effect counteracts the low‐grade inflammation, whereas in IBS‐C, it is mainly driven by interleukins.

There is higher oxidative stress and higher expression of transcription factor NF‐κB and the gp91 subunit of NADPH oxidase in IBS, with lower antioxidant regulator Nrf2. There are no differences in the IBS subtypes; however, in IBS‐C, malondialdehyde correlated with IL‐4, and TNF‐α with IL‐10, suggesting an interleukin‐mediated anti low‐grade inflammation mechanism, and in IBS‐D, GSH correlated with IL‐4, suggesting an antioxidant mechanism.