麻豆传媒

Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates fermented by colonic microbes. While fiber consumption is beneficial overall, not all fibers are alike and some IBD patients report intolerance to fiber consumption. Beta-fructan fibers are generally benign owing to their positive but they have been known to harm some patients whose microbiota has reduced fermenting capacity.

To clarify the possibly detrimental impact of beta-fructans in some IBD patients, Heather K. Armstrong, PhD, MSc, of the University of Manitoba in Winnipeg, Canada, and colleagues conducted a complex laboratory study gauging variability in fermenting capacity among IBD patients.

Armstrong discussed the rationale and findings of the study, which was recently published in .

What was the hypothesis that prompted your group to undertake this study?

Armstrong: Given reproducible evidence of reduced fiber-fermenting microbes in IBD patients, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind to host cell receptors, subsequently promoting gut inflammation.

Our hypothesis was driven by a desire to better understand the reason why certain IBD patients express intolerance to a high-fiber diet. Fibers are not digested, they are fermented by gut microbes, including bacteria and fungi. Changes in the microbiome in the gut of IBD patients have been linked to reduced fiber fermentation, leading some IBD patients to have increased amounts of remaining unfermented fiber in the gut. But what happens to these fibers remained unknown.

Studies demonstrating that dietary fiber is beneficial also show that this benefit is a result of the fermentation of fibers into beneficial short-chain fatty acids (SCFAs), suggesting that if a patient's gut microbes cannot ferment these fibers, the presence of increased unfermented fibers and reduced production of SCFAs may not be a good thing. Further studies looking at how the body responds to fungal infections showed that whole fiber-like complex sugars on the surface of fungal cells interact with immune cells to promote inflammation, which in turn suggested that if dietary fibers are not fermented in the gut in IBD patients, these fibers could interact with immune cells in the gut, promoting gut damage and worsened symptoms.

What is known about beta-fructan fibers in IBD?

Armstrong: There are many laboratory and ongoing clinical studies that examine beta-fructans in IBD, including some of our own. We previously published a review of in IBD. Briefly, we understand that beta-fructans are commonly found in plant sources including artichokes, asparagus, and bananas. A number of bacterial and fungal species have been shown to be responsible for fermentation of beta-fructans. As a prebiotic, these fibers have demonstrated benefits for the treatment of intestinal inflammation in mouse models of IBD, reducing symptoms or preventing relapse in mice that were fed beta-fructans. It is important for future studies to recognize that consuming beta-fructan in these models resulted in fiber fermentation, so the SCFAs are likely driving the benefits, not the beta-fructan itself.

Interestingly, while the polysaccharide inulin has been demonstrated to have positive effects on inflammation in select situations such as the breakdown of beta-fructan and production of SCFAs, a number of studies have also suggested that inulin can exacerbate the severity of colitis in interleukin-10- and dextran sodium sulfate-induced models of colitis and promote carcinoma in mice. These conflicting results further fueled us to perform our study to better understand what might drive inflammation in this setting.

Have IBD patients been traditionally warned to avoid fibers or advised to consume them as beneficial?

Armstrong: Patients were once told to avoid a high-fiber diet; however, with a growing understanding that dietary fibers are healthy in healthy individuals, it has been largely assumed this translates to IBD patients also. One serious issue with prior studies is that many perform clinical correlations only; many examine dietary fiber generally without defining which specific dietary fibers they examined, and many utilize animal models that are capable of fiber fermentation, which does not appropriately reflect the IBD gut.

Our work and that of others has begun to demonstrate key differences between the diverse types of dietary fibers, and our recent study now supports the mechanisms underlying the detrimental effects of beta-fructan in a setting where fiber fermentation by microbes is limited.

How did you design and conduct the study?

Armstrong: Dr. Eytan Wine and I designed the study, which was ultimately supported by many experts in the field through collaborations. The study has a complex design, using laboratory-based models, clinical samples cultured ex vivo using blood, biopsies, and gut washes, and mechanistic findings. We validated samples in our randomized controlled trial cohort of ulcerative colitis patients in remission who consumed placebo or beta-fructans for 6 months.

What were the main findings and what foods would be best avoided by IBD patients?

Armstrong: Unfermented dietary beta-fructan fibers induced inflammatory cytokines in a subset of IBD patients via interactions with specific immune pathways such as toll-like receptor 2 and activation of the inflammasome NLRP3. Results were validated in a randomized controlled trial of adults in remission from ulcerative colitis, which examined beta-fructan supplementation at 15 g/day for 6 months compared with placebo. Fermentation of beta-fructans by human gut whole-microbiota cultures reduced the pro-inflammatory response, but only when microbes were collected from non-IBD or inactive IBD patients. This suggests that beta-fructans may be beneficial for IBD patients whose gut microbes are capable of fermenting beta-fructans into SCFAs, while these same fibers are detrimental in IBD patients whose gut microbes are not able to ferment beta-fructans.

Our team is currently performing a large multicenter clinical study that aims to better uncover the clinical relevance of these findings and to help us determine how we can best identify those patients who are sensitive to beta-fructans, resulting in a personalized approach.

Are the results ready to be incorporated into everyday clinical care?

Armstrong: Not immediately; however, clinical studies are now warranted and hopefully other research teams will use our findings to better design their own studies in future, keeping in mind that some IBD patients will benefit from select dietary fibers in their diet, while others will possibly suffer. Therefore, lumping all patients together when examining clinical outcomes could lead to variability in results, depending on the percentage of patients in their clinical cohort who are sensitive to fibers owing to altered microbial fermentation processes.

What questions still remain to be answered?

Armstrong: This is only the tip of the iceberg, and it is fantastic to see growing attention to improving our understanding of dietary fibers in health and disease; however, studies must be designed more appropriately in the future, with fermentation processes being considered in mouse and human studies. Also, the type of fiber studied is essential when it comes to outcomes.

What is the overall message to send to gastroenterologists treating this patient population?

Armstrong: Sensitivity to dietary fibers cannot be ignored. If a patient is experiencing worsened symptoms following consumption of certain grains, fruits, or vegetables, it may be the result of an inability to ferment fibers in their gut owing to altered microbes and interactions between specific fibers and gut cells, especially when there is active disease. Access to dietitians is essential for IBD patients, and it is worth discussing low-residue diet options that reduce consumption of foods the patient is sensitive to, while at the same time increasing dietary fiber consumption where possible to support both host and microbe gut health.

You can read the abstract of the study here, and about the clinical implications of the study here.