Characterisation of the Plasma and Faecal Metabolomes in Participants with Functional Gastrointestinal Disorders 2024 Fraser et al

[Andy]

Abstract

There is evidence of perturbed microbial and host processes in the gastrointestinal tract of individuals with functional gastrointestinal disorders (FGID) compared to healthy controls. The faecal metabolome provides insight into the metabolic processes localised to the intestinal tract, while the plasma metabolome highlights the overall perturbances of host and/or microbial responses.

This study profiled the faecal (n = 221) and plasma (n = 206) metabolomes of individuals with functional constipation (FC), constipation-predominant irritable bowel syndrome (IBS-C), functional diarrhoea (FD), diarrhoea-predominant IBS (IBS-D) and healthy controls (identified using the Rome Criteria IV) using multimodal LC-MS technologies.

Discriminant analysis separated patients with the ‘all constipation’ group (FC and IBS-C) from the healthy control group and ‘all diarrhoea’ group (FD and IBS-D) from the healthy control group in both sample types. In plasma, almost all multimodal metabolite analyses separated the ‘all constipation’ or ‘all diarrhoea’ group from the healthy controls, and the IBS-C or IBS-D group from the healthy control group. Plasma phospholipids and metabolites linked to several amino acid and nucleoside pathways differed (p < 0.05) between healthy controls and IBS-C. In contrast, metabolites involved in bile acid and amino acid metabolism were the key differentiating classes in the plasma of subjects with IBS-D from healthy controls. Faecal lipids, particularly ceramides, diglycerides, and triglycerides, varied (p < 0.05) between healthy controls and the ‘all constipation’ group and between healthy controls and ‘all diarrhoea’ group.

The faecal and plasma metabolomes showed perturbations between constipation, diarrhoea and healthy control groups that may reflect processes and mechanisms linked to FGIDs.

Open access

 

[Sean]

There is evidence of perturbed microbial and host processes in the gastrointestinal tract of individuals with functional gastrointestinal disorders (FGID) compared to healthy controls.

So when you will stop calling them functional disorders?

 

[rvallee]

functional diarrhoea

I read stuff like this and I can't tell if I'm reading the deep sewers of brain-dead conspiracy communities or something seriously. Because I can't tell the difference.

And all I can think is that the world hasn't gone mad, it clearly always was.

 

[Joan Crawford]

If they dunno what causes something, why not just call it idiopathic.

Not hard.

I / we dunno. We're trying to figure it out...... OK. Adding functional just looks like they have zero knowledge of the history of medicine, especially women

 

[Yann04]

idiopathic

I guess when you’re making a career out of publishing about a syndrome and claiming you can treat it, it’s inconvenient to say the cause is unknown.

There’s a general trend of lack of humility, acceptance that medical models are still very oversimplified compared to reality, in medicine.

 

[Eleanor]

I guess when you’re making a career out of publishing about a syndrome and claiming you can treat it, it’s inconvenient to say the cause is unknown.

Also the idea that the patient will feel better and recover if you confidently "reassure" them by telling them any old explanation for their symptoms, whereas telling them the non-reassuring truth that you don't know the cause will scare them and make them stay ill.

 

[Peter T]

Also the idea that the patient will feel better and recover if you confidently "reassure" them by telling them any old explanation for their symptoms, whereas telling them the non-reassuring truth that you don't know the cause will scare them and make them stay ill.

There is the old idea that the patient’s belief in their doctor is part of the curative process. The idea that patients are more likely to improve if they have blind faith rather than actually understand the reality of their condition.

Thirty years ago with such as MND (ALS) you had to fight for patients to be told the truth, to convince doctors that patients could only plan for and manage their decline if they knew the likely prognosis, though once doctors realised that despite there being no curative treatments that there was a tremendous amount that could be done to maintain communication, maintain nutrition, maintain functional independence, etc they did usually come round.

I agree this still persists in relation to ME/CFS in the belief the more false hope a person has the better they will do, which means we can go for years if not decades knowing nothing about such basic ideas as PEM, orthostatic intolerance, etc.

 

[Ravn]

It is seriously annoying the term functional has been hijacked by the double-speak crowd. Every time you see it you have to double-check which meaning applies. Double the effort

In this instance the term functional is being used in its neutral form simply indicating some form of signalling or metabolic dysfunction - as opposed to detectable tissue damage - but without any suggestion that the patient can think themselves out of the dysfunction

The only reference to psych is this

The gut-brain axis is a critical communication network that influences both digestive function and mental health. Disturbances in this axis, including changes in gut microbiota and nutrient absorption, can exacerbate or lead to mental health issues like anxiety, depression, and stress-related disorders. For instance, FGIDs are prevalent in individuals with eating disorders and may perpetuate or arise from disordered eating behaviours [47]. Mechanisms such as nutrient sensing and microbiota changes influence the interaction between the gut and the brain, highlighting the need for further research into how dietary therapies can manage both gastrointestinal and psychiatric symptoms.

More concerning to me (tongue in cheek) is that the lead author is affiliated to AgResearch strengthening my suspicion that in NZ it's the agricultural research institutes who get the best tech to play with

ME gets a couple of mentions, I wonder how it appeared on their radar? A first sign of ME papers becoming mainstream? Or one of the authors having some connection to someone affected? I don't recognise any of the names but one is based in Dunedin so could have come across Prof Tate there

These findings agree with the increased concentrations of ceramides, glycosphingolipids, diglycerides, and triglycerides reported in mucosal biopsies and plasma samples of individuals with IBS compared to healthy controls [16] and also in individuals with myalgic encephalomyelitis/chronic fatigue syndrome coupled with IBS [17].

Ceramides are waxy lipids associated with pain sensitivity, cell toxicity, inflammation, and various diseases, such as metabolic disorders, Alzheimer’s disease, insulin resistance, and inflammatory bowel diseases [16,17]. Kajander et al. showed that the relative intensity of lipids in the ceramide and sphingomyelin pathways was increased in IBS participants (all subtypes combined) compared to healthy controls [16]. In individuals with myalgic encephalomyelitis or chronic fatigue syndrome (often associated with IBS), changes in the gut microbiome were associated with increased faecal lipopolysaccharide concentrations [16]. This increase may trigger sphingomyelinases that, when hydrolysed, form ceramides [17,24], contributing to oxidative stress and intestinal barrier dysfunction [16].

 

[rvallee]

There is the old idea that the patient’s belief in their doctor is part of the curative process. The idea that patients are more likely to improve if they have blind faith rather than actually understand the reality of their condition.

Ironically, the most common outcome I see of this is that people end up thinking that physicians are idiots and stop trusting them entirely. Which makes physicians even more defensive, and offensive about it in the process.

One of those cases where ignorance truly is bliss, just entirely one-sided.