Abstract

Background: The Rome V criteria for irritable bowel syndrome (IBS) were proposed in May, 2026. Their performance for the diagnosis of IBS in clinical practice is as yet unknown. We aimed to conduct a diagnostic accuracy study to examine this issue.

Methods: This diagnostic accuracy study was conducted in the specialist IBS clinic in Leeds Teaching Hospitals National Health Service Trust, Leeds, UK. Consecutive adults aged 16 years and older who were referred with suspected IBS between Sept 22, 2016, and June 18, 2024, provided complete symptom data. We applied standardised investigations (including full blood count, C-reactive protein, and coeliac serology), with assessors masked to symptom status. We assessed performance of the Rome V criteria, compared with the previous iterations, Rome IV and Rome III. The reference standard used to confirm IBS was the presence of lower abdominal pain or discomfort in association with altered stool form or frequency combined with no evidence of organic gastrointestinal disease after standardised investigations. Sensitivity, specificity, and positive and negative likelihood ratios were calculated for each of the diagnostic criteria, with 95% CIs.

Findings: Of the 745 eligible patients recruited, 726 patients had complete Rome V symptom data (546 [75%] were female, 180 [25%] were male, and mean age was 36·9 years [SD 14·0]). 417 (57%) patients met Rome V criteria for IBS. The level of agreement between the Rome V and either the Rome III or Rome IV criteria was fair to moderate (κ=0·36-0·55). Of patients with complete Rome V symptom data, 590 had IBS according to the reference standard, of whom 390 met Rome V criteria for IBS. Sensitivity of the Rome V criteria was therefore 66·1% (95% CI 62·1-69·9) and specificity was 80·1% (72·4-86·5). Positive likelihood ratio for the Rome V criteria was 3·33 (95% CI 2·40-4·74) and negative likelihood ratio was 0·42 (0·37-0·49). The Rome III and Rome IV criteria for IBS performed differently, with sensitivities of 87·5% (95% CI 84·4-90·3) and 78·9% (75·4-82·1) and specificities of 75·0% (66·3-82·4) and 81·0% (73·4-87·2). Positive and negative likelihood ratios for the Rome III criteria were 3·50 (2·61-4·84) and 0·17 (0·13-0·21) and for the Rome IV criteria were 4·16 (2·98-5·95) and 0·26 (0·22-0·31).

Interpretation: The Rome V criteria for IBS identified a different group of patients, with lower sensitivity than either Rome III or IV criteria in this single centre secondary care study. The clinical relevance of this is uncertain.

Highlights

• Nav1.8 G1662S gain-of-function mutation was identified in humans with neuropathic pain.
• GS mutant channels amplify nociceptors excitability by enhancing Na^(+) influx and promoting repetitive AP firing.
• The biophysical mechanisms of GS-induced neuronal hyperexcitability are context-dependent.
• At low firing rates, G1662S-depolarized inactivation drives hyperexcitability.
• At high firing rates, G1662S-altered repriming kinetics become equally important.

Abstract

Voltage-gated sodium channel Nav1.8 is highly expressed in nociceptors, where it plays a critical role in sustaining repetitive action potential (AP) firing. Gain-of-function Nav1.8 mutations that increase nociceptor excitability have been identified in patients with painful peripheral neuropathy, but the biophysical mechanisms by which they confer nociceptor hyperexcitability are incompletely understood. Here we carry out a high-resolution dissection of the functional consequences of a Nav1.8 mutation (G1662S) identified in human subjects with severe neuropathic pain, using dynamic clamp modeling in small dorsal root ganglion (DRG) neurons. While Nav1.8WT/GS conductance did not alter resting membrane potential, rheobase, or single AP threshold, it produced a marked hyperexcitability during repetitive firing. Nav1.8WT/GS neurons generated nearly twice as many APs as wild-type controls in response to suprathreshold depolarization, an effect attributable to increased sodium charge transfer across successive spikes. Charge analysis revealed that the GS mutation disproportionately enhanced suprathreshold sodium influx, supporting greater AP fidelity without adaptation. Biophysical dissection showed that this excitability phenotype arises from frequency-dependent mechanisms: at lower firing frequencies, the depolarizing shift in steady-state inactivation increases channel availability and contributes to G1662S-mediated hyperexcitability, whereas at higher firing frequencies both the depolarized voltage-dependence of inactivation and the accelerated recovery from inactivation further sustain G1662S hyperexcitability. Together, these properties enable Nav1.8WT/GS neurons to maintain enhanced firing across a broad range of frequencies, in contrast to wild-type nociceptors that typically adapt faster. These findings provide mechanistic insight into Nav1.8-driven hyperexcitability and highlight Nav1.8 as a therapeutic target for genetic and acquired pain syndromes.

https://clinicaltrials.gov/study/NCT07655375?cond=Irritable%20Bowel%20Syndrome&viewType=Card&rank=4

Study Overview

Brief Summary

Study evaluating the effect of UCB8600 on mast cell activation in the human gut:

IBS is a disease characterized by abdominal pain and a change in stool. Treatment is limited to an adapted life style, dietary changes and medication to lessen cramps (spasmolytica), all of which have seen limited to no clinical success.

Recently, we were able to demonstrate that mast cells play an active role in IBS symptoms. More specifically, they set histamine free when activated which heightens nerve sensitivity in the intestines which probably contributes to the abdominal pain. A new product called "UCB8600" is hypothesized to be able to counteract this by causing less mast cells to be activated. In this study we'll test this by administering UCB8600 on intestinal tissue and see if there is less mast cell activation. If the study produces good results, this new product could potentially be used as a treatment for IBS in the future.

https://preview.redd.it/3oul4czknfah1.png?width=919&format=png&auto=webp&s=ce6adc8de56fae5e99ad455f1444acbf9449b8a3

I'm a 34-year-old woman, and I'm trying to figure out if anyone has had a similar experience.

For about a year, I've had intermittent lower right abdominal discomfort. In the beginning it would mostly happen if I ate too much, then it would pass and I'd feel normal again. Over the past few weeks, it seems like it's become more noticeable.

The discomfort is usually dull rather than severe. It seems to come and go instead of being constant. Sometimes I wake up feeling completely fine, but then the discomfort starts when I need to have a bowel movement. It often eases up afterward, although I can still have mild spasms or lingering discomfort.

I've also had periods of constipation where fiber seems to help. My stools are generally formed, although sometimes they're smaller than normal. I haven't noticed blood in my stool or black stools.

One thing I've wondered is whether smoking cigarettes made everything worse. I had been smoking more regularly for a while, and it seems like my stomach problems became more noticeable around that time.

I'm planning to see my primary care doctor, but in the meantime I'm curious:

• Has anyone had IBS or constipation start this way?
• Did your symptoms gradually progress over a year?
• Did quitting smoking, changing your diet, or treating constipation make a significant difference?

I'm looking for personal experiences, not a diagnosis. Thanks!

Hello Everyone!

This is a goodbye post. 2 days ago I had 5 beers with my friends and I had no diarrhea or crazy gas and I thought yes that confirms it, I can put this behind now. So behold, it will be long post!

I had IBS for 10 years, then I cured myself. Everybody keeps saying do not say cured; say 'in remission' or 'treated'. No, I am cured. It has been 5 years now. Stop with the despair, I hate that. A lot of people here just gives in to depression, and is ready to give up so easily it honestly annoys me.

This is not a hopeless disease with no cure. The problem is, it is an umbrella term; whatever they cannot identify properly, they just label as IBS. It is bullshit!

Why does that happen though? Well, you have a set of symptoms which could be cause by many things such as SIBO, gut-microbiome disruption, BAM, post-infectious damage, gut-brain axis issues etc. In many parts of the world, you just get a 10 min discussion, and if you are lucky you get tested for a thing or 2, but then both the doctor and you just give up.

I really think that if you had a team like House MD's team testing and treating you for everything from most likely to least likely, you would eventually find your cure. Yes, cure! Not remission, not symptom-free, not some other bullshit word. Cured...

My Story

Let me tell you a bit about my story. I had IBS-D for 10 years and I just kept fighting against it. I have learned everything by reading and asking the doctors, and getting tested. I had many "clean" endoscopies, colonoscopies, breath tests, stool tests yada yada yada. All came back clean. Well nothing about IBS felt clean. There were many times I thought to myself "If this is life, I am ok not to live.". That was wrong because I had fallen into the same depression trap that we all fall at some point. Things feel hopeless and we just give up.

But my character is a bit persistent, so I got out of the depressive episodes quickly. I have tried so many stupid things you would not believe it. 90% of them did not work. I have wasted my time, wasted my money, risked my health.

I used many antibiotics, drank epsom salt - olive oil mixture, used a FULL bottle of -advertised as!- miracle probiotics, drank full glass of milk before going to bed because someone said it helped them. Antibiotics further destroyed my microbiome, that epsom salt mixture made me shit tiny stones, that probiotics did nothing but give me cold chills, and the milk gave me so much gas I was about to float.

DO NOT follow other people's posts, comments blindly. WHAT WORKED SOMEONE MOST PROBABLY WILL NOT WORK FOR YOU. Unless you have the exact same story as them, it is very unlikely.

It was not all bad though; I have tried L-glutamine for gut lining, Vitamin D+K for immune support, tried coupel of basic store-bought probiotics, heavily drank/ate kefir, yoghurt with live cultures, pickles. Cut dairy and sugary snacks as much as I could. Got prescribed rifaximin for SIBO. All these helped but mostly as shots in the dark. I got lucky.

You know what I have not tried that could easily helped me when I was so anxious to go to that tiny classroom of 10 people because I was sure that everybody would hear the growling coming from my stomach? Psyllium husk. Enteric-coated peppermint capsules daily. Nobody recommended these and I could have just managed my day-to-day at least.

In the end I discovered that I had persistent SIBO. Rifaximin would fix it, but without the proper dieat, microbiome support, and working out; I would go back to square 1. It took me 10 years to realize this and break the cycle, but I did.

My Recommendation

FOR THE LOVE OF GOD, 2 GOLDEN RULES:

1) Do not give up. You do not have any terminal illnesses. This is just a complicated "umbrella" term that we get thrown, because many healthcare systems do not spare more than 10 mins per person. Many of us cannot even talk to the same doctor the next time. You have to be your own doctor.

2) Do not try things blindly. Do not look for a miracle pill, do not look for a miracle app. Do the work, be your own investigator. Treat your disease like a case to crack.

Just make sure you follow a path like this.

1) Understand what IBS is.

2) Understand IBS subtypes, and which one is yours.

3) Learn how to manage your symptoms today. Immediate relief based on subtype.

4) Learn how to stabilize your symptoms. Things that can help you in couple of days-weeks but are more stable in effect. Not a cure, just symptom treatment to keep living your life.

5) Check your diet. Jump on the FODMAP train, it is proven; but identify your trigger foods and do reintroduction. Do not just blindly skip eating anything on FODMAP list; often times it is just couple of the foods that trigger you.

6) Start your investigation. One topic at a time. Look back on the first time it started; did you get an infection? Did you lose a family member at that time? Is there anything you can tie to this? What are your specific symptoms? Does it fit to SIBO? IF yes, then go to your doctor and ask for the treatment. That did not work? Ok, next try post-infectious. No luck? That is fine, next try BAM? Always check with your doctor; they are not your enemies. The system jsut pushes them to be insanely efficient by sparing little time for the conversation with the patients.

7) When you find your cure or remission or nirvana or whatever you call it: How to stay healthy in that cured/remission state.

You get the idea. You do not need a miracle. You need structure. Do the work, and you will be free.

My Parting Gift

I will be honest with you: I have started working on an e-book for IBS as a side gig. A friend of mine asked me for advice, and at that time I realized how much I learned. And then using ai for research I have consolidated all that and created the book. I have also tried creating a youtube channel as the book is a bit heavy, but half-way through I got burned out. So I will not finish that.

I am not a doctor, I am a regular person; but everything mentioned in the book are based on actual studies done by real scientists. You can check the resources.

The book is absolutely free forever in this google drive link, hope it helps somebody: link

I am not selling you anything, but I want just one thing from you: Don't give up. Keep investigating!

TLDR: I had IBS for 10 years and am now cured. I am saying goodbye, there is a free book if you want with my humble wisdom attached to it. Good luck!

These data showed that the majority of patients (90.9%) in the study were opioid free through the end of treatment (up to 14 days), demonstrating the potential for JOURNAVX as a core element of opioid-free multimodal treatment for moderate-to-severe acute pain after aesthetic and reconstructive procedures. In contrast, the literature shows opioid-free rates of less than 10% with multimodal treatment without JOURNAVX.

https://www.thelancet.com/journals/langas/article/PIIS2468-1253(26)00116-0/fulltext

Summary

Background

Eosinophilic gastritis currently has no approved treatments and is postulated to be driven by type 2 inflammation. Dupilumab blocks type 2 cytokines IL-4 and IL-13 and has efficacy in multiple diseases characterised by type 2 inflammation, including eosinophilic oesophagitis. We aimed to assess the efficacy and safety of dupilumab in patients with eosinophilic gastritis.

Methods

DEGAS was a proof-of-concept, phase 2, multicentre, randomised controlled trial consisting of a 12-week, double-blind, placebo-controlled period, followed by a 24-week open-label extension period. Patients aged 12–70 years from 11 hospitals in the USA with histologically active eosinophilic gastritis (≥30 eosinophils per high-power field [HPF] in at least five HPFs in the gastric antrum and/or body) and moderate-to-severe symptoms occurring at least 2 days per week in the 2 weeks before screening were recruited. Patients with current or recent use of any biologic or current use of systemic steroids at a dose of more than 10 mg/day (prednisone) were excluded. Eligible patients were individually randomised (1:1) to parallel groups and received six injections over 12 weeks: subcutaneous dupilumab (600 mg once followed by 300 mg every 2 weeks) or subcutaneous placebo. Randomisation was performed using a central variable block (block sizes permuted between 2 and 4), with stratification by age (12–17 years or ≥18 years) and use (yes or no) of either systemic corticosteroids, swallowed corticosteroids for eosinophilic gastritis, or non-steroidal systemic immunosuppression therapy. Throughout the duration of the study, patients were expected to maintain their treatments or diets for eosinophilic gastritis. All patients who completed the double-blind period could enter the open-label extension at week 12, during which both groups received dupilumab until week 34. The primary endpoint of relative change from baseline in mean gastric eosinophil count from the five most eosinophil-dense HPFs in the gastric antrum and/or body was analysed at week 12 using linear regression. Secondary endpoints included absolute changes from baseline in Eosinophilic Gastritis Histologic Scoring System (EoS-HSS) total score, mean gastric eosinophil count from the five most eosinophil-dense HPFs, and Eosinophilic Gastritis Endoscopic Reference System (EoG-REFS) total score. All randomly assigned patients who received at least one dose of study drug were included in the safety analysis and efficacy analyses were done in all randomly assigned patients who received at least one dose of study drug and had outcome data available at week 12 (complete case). This study is registered with ClinicalTrials.gov (NCT03678545) and is now complete.

Findings

Between May 14, 2021, and Nov 10, 2023, we randomly assigned 41 patients, of whom 21 (51%) received dupilumab and 20 (49%) received placebo during the double-blind period and were included in the safety analysis. Patients were aged 12–59 years (mean 30·5 years [SD 13·2]; seven [17%] aged <18 years), 37 (90%) were White, one (2%) was Asian, one (2%) was Black or African American, two (5%) were of multiple races, 25 (61%) were female, and 16 (39%) were male. One patient from the placebo group withdrew before week 12; the remaining 21 patients treated with dupilumab and 19 patients treated with placebo had available data and were assessed for the primary endpoint. At week 12, the relative reduction in the primary endpoint was greater with dupilumab (estimated mean change –50% [95% CI –66 to –34]) than with placebo (–4% [–20 to 13]; difference –47 percentage points [–70 to –24]; p<0·0001). Significant differences between groups were noted for the secondary endpoints of absolute change from baseline in EoS-HSS total score (difference –0·10 [95% CI –0·18 to –0·03]; p=0·0055), absolute change from baseline in mean gastric eosinophil count (–38·8 [–75·6 to –17·8]; p=0·0008), and absolute change from baseline in EoG-REFS total score (–3·42 [–6·18 to –0·65]; p=0·016). At week 12, the incidence of treatment-emergent adverse events was similar between dupilumab (17 [81%]) and placebo (17 [85%]). The most common adverse event was blood eosinophilia, with similar incidence in the dupilumab (six [29%]) and placebo (six [30%]) groups. No serious adverse events or treatment-related deaths were reported.

Interpretation

The improvement of histological outcomes of eosinophilic gastritis with dupilumab in this proof-of-concept study shows type 2 inflammatory involvement in the disease and the potential value of dupilumab for the treatment of eosinophilic gastritis.

Abstract

OBJECTIVES:
Fibromyalgia (FM) is a multisystem disorder frequently associated with functional gastrointestinal disorders, particularly irritable bowel syndrome (IBS). Diet-related factors and gut microbiota alterations, key elements in IBS pathophysiology, may disrupt the gut-brain axis, promoting immune activation, altered pain processing, and peripheral nerve dysfunction, including small fibre involvement, which has been consistently reported in FM. The study investigated whether IBS symptom severity in FM is associated with clinical and psychological features and with neuropathological evidence of small fibre involvement.
METHODS:
In this monocentric cross-sectional observational study, 89 FM patients underwent clinical and psychological assessments. IBS severity was assessed using the IBS Severity Scoring System (IBS-SSS). Skin biopsy with quantification of intraepidermal nerve fibre density (IENFD) at proximal and distal sites was performed in 57 patients. Patients were classified into mild-moderate and severe IBS groups. Between-group differences were analysed using Mann-Whitney U and χ² tests. Spearman’s rank correlation served to assess associations between IBS severity, clinical variables, and IENFD.
RESULTS:
Severe IBS symptoms were present in 47.1% of patients. Compared with patients with mild–moderate IBS, those with severe IBS showed higher widespread pain index (WPI) and symptom severity scale (SSS) scores, indicating greater fibromyalgia severity, as well as increased anxiety and depressive symptoms, reduced sleep duration, and greater functional impairment (all p<0.05 after FDR correction). Skin biopsy revealed a higher prevalence of reduced IENFD, particularly at proximal sites, in severe IBS patients. Notably, IBS-SSS scores were negatively correlated with proximal IENFD (r=-0.34, p=0.01).
CONCLUSIONS:
IBS severity identifies a clinically more severe FM phenotype with small fibre pathology. These findings are consistent with a possible interaction between gastrointestinal dysfunction and peripheral nerve involvement in FM, although mechanistic pathways require further investigation.

https://research.kuleuven.be/EU/p/he/p1/erc/macpain

About the project

Chronic abdominal pain is a major symptom of irritable bowel syndrome (IBS), a gastrointestinal disorder that, depending on the diagnostic criteria used, affects 4 to 20% of the population, with a female to male ratio of 2. It is characterized by altered bowel habits associated with abdominal pain in the absence of an organic cause. Despite its high prevalence and significant impact on quality of life, insight in its pathophysiology is rather limited. Consequently, treatment is disappointing and restricted to efforts aimed at correcting altered defecation, however this approach leaves abdominal pain largely unaffected. Pain arising from the gastrointestinal tract is detected by afferent nerve fibres with their cell bodies located in the dorsal root ganglia (DRG). My team recently discovered that mast cell activation in response to food intake results in the release of histamine, which renders DRG neurons more excitable leading to increased pain signalling, also referred to as visceral hypersensitivity (VHS). The clinical relevance of this finding is supported by the observation that treatment with antihistamines improves abdominal pain in about 50% of IBS patients. In MACPAIN, I aim to discover new therapeutic targets to treat the remaining 50%. Of interest, DRG neurons are surrounded by resident macrophages with which they closely interact. I hypothesize that repetitive peripheral activation of DRG neurons leads to the release of macrophage modulating mediators ultimately leading to persistent alterations in resident macrophage function and chronic VHS. Using state-of-the-art methods, we will first interrogate the impact of repetitive afferent nerve activation on the DRG macrophage population to subsequently unravel the mechanisms leading to chronic VHS. These groundbreaking insights will allow us to identify novel therapeutic targets to treat chronic VHS and will pave the way for the development of new therapeutic compounds for IBS.

Main funding info

• Programme Funding: Horizon Europe
• Sub Programme Area: ERC-2025- AdG
• Project Reference: 101265243
• From: in grant preparation
• Budget: 2.151.250 EUR
• Contract type: ERC-AdG

Abstract

We previously reported the discovery of a multipronged sodium channel-inhibitory peptide aptamer (NaviPA1), derived from the intracellular disordered sequence conserved among tetrodotoxin-sensitive (TTXs) NaVs, for AAV-mediated sensory neuron-targeted analgesia in rat models of chronic pain. In this study, an initial translational effort was undertaken, including 1) removing GFP from the AAV transgene cassette and enhancing small peptide NaviPA1 molecular engagement by constructing a concatemeric NaviPA1 (CoNaviPA1) containing two copies of consensus NaviPA1 as a tandem repeat, and 2) evaluating long-lasting preclinical analgesic effectiveness in rats by injecting AAV-CoNaviPA1 into the sciatic nerve in a rat model of tibial nerve injury-induced painful neuropathy. Results showed analgesic efficacy that persisted for 3-4 months of observation, with magnitudes and time courses comparable between male and female rats. AAV genome analysis confirmed the peripheral nerve-restricted biodistribution of AAV-CoNaviPA1 and long-term transgene expression. Inhibition of TTXs NaV channels and suppression of action potential firing by CoNaviPA1 were demonstrated in human sensory ganglia neurons, underscoring the translational potential of AAV-mediated CoNaviPA1 expression in the peripheral sensory pathway for treating intractable chronic neuropathic pain conditions resistant to current therapies.

Graphical abstract

A very interesting review (link is in first comment below to avoid tripping filters) has explored the current understanding of IBS pathophysiology, diagnosis, and treatment, with a focus on the role of histamine in gastrointestinal disorders.

Histamine is a chemical messenger your immune system releases. It's involved in allergic reactions, inflammation, and digestion. Histamine also regulates your sleep-wake cycle and cognitive function.

And histamine is key to gastrointestinal motility, visceral hypersensitivity, and immune system dysregulation.

The review also addresses histamine’s potential as a therapeutic target in IBS pain management.

Abstract

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness marked by fatigue, cognitive impairment, and post-exertional malaise. Gastrointestinal (GI) symptoms are frequently reported, yet their relationship to central features of the illness and biological correlates remains poorly understood.

Objectives

We aimed to characterize GI symptom burden in ME/CFS and evaluate its associations with core clinical features and specific immune and inflammatory markers, with attention to potential gut-related contributions to disease expression.

Methods

GI symptoms and 49 additional symptoms across nine domains were assessed in 116 ME/CFS patients and 80 matched controls. Plasma C-reactive protein (CRP) and antibodies against dietary and microbial antigens were measured as indicators of systemic inflammation and putative gut-derived antigen exposure.

Results

ME/CFS patients reported significantly elevated GI symptom frequency and severity compared with controls, with 53% of ME/CFS patients versus 8% of controls reporting a prior diagnosis of irritable bowel syndrome. GI symptom burden correlated with fatigue, cognitive difficulties, flu-like symptoms, pain, sleep disturbances, neurological complaints, and sensory sensitivities, independent of illness duration. CRP levels were higher in patients with greater GI symptoms and correlated with GI, fatigue, musculoskeletal pain, and flu-like symptom burden. Patients with greater flu-like symptom expression exhibited higher IgM responses to dietary gliadin and bacterial lipopolysaccharide. These associations were not detected in controls.

Conclusions

GI symptoms are a prominent, clinically relevant dimension of ME/CFS, associated with broader symptom burden and inflammatory heterogeneity. These findings highlight the relevance of gut-related and immune processes in ME/CFS and underscore the value of incorporating GI symptom assessment in translational studies to help refine mechanistic understanding and improve therapeutic stratification.