Professor El-Omar has chosen Professor Robin C Spiller to do the next #GUTBlog. Professor Spiller is a Professor of Gastroenterology in the Gastrointestinal and Liver Disorders Theme, in the Nottingham NIHR Biomedical Research Centre, Queen’s Medical Centre, Nottingham, UK. The #GUTBlog focusses on the latest paper “Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies” which was published in paper copy in GUT in June 2022.

Professor Spiller writes:

“We have known for many years that psyllium, also known as ispaghula, improves IBS symptoms but the trial showing this¹ only reported global symptoms and used unselected patients so the mechanisms of the effect was unclear. However the difference between active and placebo in “satisfactory relief” outcome of 29% was note worthy. Almost certainly because it was an off patent product, the pharmaceutical industry did not promote this widely and instead put their efforts into much more targeted small molecule approaches. These typically generate increments over placebo of around 15%, much smaller than ispaghula. We had some inkling of possible mechanisms of ispaghula’s effects from a study done using scintigraphic imaging in a lactulose –induced diarrhoea model for IBS with diarrhoea characterised by accelerated ascending colon transit. That study showed that psyllium moderated the laxative effect of lactulose, delaying both oro-caecal and ascending colon transit. At that time we knew little of the events in the colon underlying these effects. Two decades later we have much more powerful tools including MRI to assess colonic volumes, content and transit. Our previous studies had shown us that psyllium has a big effect in the small bowel, increasing the water content and delivering more water to the ascending colon whose contents became more watery², something we can now measure non-invasively using the MRI time constant, T1. We had also performed an MRI study comparing wheat bran and nopal, a cactus fibre and psyllium, all laxatives which increase the ascending colon water content. While wheat bran and nopal were both rapidly fermented as shown by a marked rise in breath hydrogen when they reached the ascending colon, psyllium was not, nor did it increase colonic gas as the other two fibres did³. The increased flatulence and bloating associated with bran is one reason why patients are not so keen on it, despite its effectiveness as a laxative.  Although the low FODMAP diets have proved highly popular with both IBS patients and dietitians we had concerns from previous work at King’s College that they reduced the population of Bifidobacteria and potentially other microbiota thought to be beneficial to health⁴. Knowing that psyllium was resistant to degradation by the colonic microbiota lead us to wonder  what would happen if we co-administered psyllium with a classic FODMAP inulin, which in high doses causes flatulence and gas symptoms in most people. We hypothesised that it would slow fermentation and possibly shift it to the left side of the colon which might have health benefits such as delivering more anti-neoplastic short chain fatty acids (SCFAs) to this region, which is where most colon cancers arise.

As our recent study⁵ showed psyllium is fermented to a very limited degree in the colon, does not produce increased colonic gas and indeed markedly reduced the amount of gas produced by co-administered inulin. Further understanding the precise mechanism is now subject of an ongoing MRC funded project. Our current belief is that it is the sudden rise in nutrient after an overnight fast which leads to an overproduction of reducing equivalents which are removed from the microbiota as hydrogen gas. If we could slow this process we believe these reducing equivalents would be converted into acetate and other non-gaseous products. Psyllium is an unusual fibre chemically which produces a viscous gel which “self heals” when disturbed by mixing. This, combined with its resistance to microbial degradation may make it particularly effective in hindering access of colonic microbes to the inulin.

The idea would be that regular dosing with psyllium could modify the response to FODMAPs and hence avoid the need for a complex, socially restrictive diet for IBS patients, which recent studies suggest would be welcomed by patients⁶. However psyllium is a natural product which varies with climate and soil so there is an attraction to achieve similar effects using modified celluloses which are more readily and economically produced in a food grade quality and already used widely in the food industry. We are now exploring this possibility using both in vivo MRI and in vitro fermentation studies to define the mode of action of psyllium and attempt to use this understanding to create cellulose mixes with similar or even superior properties.

References

1. Prior A, Whorwell PJ. Double blind study of ispaghula in irritable bowel syndrome. Gut 1987;28(11):1510-13.
2. Major G, Murray K, Singh G, et al. Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging. Neurogastroenterol Motil 2018;30(9):e13400. doi: 10.1111/nmo.13400 [doi]
3. Gunn D, Murthy R, Major G, et al. Contrasting effects of viscous and particulate fibers on colonic fermentation in vitro and in vivo, and their impact on intestinal water studied by MRI in a randomized trial. Am J Clin Nutr 2020 doi: 5867030 [pii];10.1093/ajcn/nqaa173 [doi]
4. Staudacher HM, Lomer MC, Anderson JL, et al. Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome. J Nutr 2012;142(8):1510-18. doi: jn.112.159285 [pii];10.3945/jn.112.159285 [doi]
5. Gunn D, Abbas Z, Harris HC, et al. Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies. Gut 2022;71(5):919-27. doi: 10.1136/gutjnl-2021-324784 [published Online First: 2021/08/07]
6. Rej A, Sanders DS, Shaw CC, et al. Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet and the Gluten-Free Diet. Clinical Gastroenterology and Hepatology 2022 doi: https://doi.org/10.1016/j.cgh.2022.02.045

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