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Primary Care Corner with Geoffrey Modest MD: Crohn’s Disease – Should We Recommend Eating Fiber?

23 Feb, 16 | by EBM

By Dr. Geoffrey Modest

In an observational study, researchers found that there was a decrease in Crohn’s disease flares in those on higher fiber diets (see doi.org/10.1016/j.cgh.2015.12.029​).

Details:

  • 1619 patients in the Crohn’s and Colitis Foundation of America Partners Internet cohort (an online database of more than 14,000 people with inflammatory bowel disease, IBD) completed a 26-item dietary survey. The study was limited to those in remission at baseline, with a follow-up survey 6 months later
  • 1130 patients had Crohn’s disease– CD (30% male, 46% had surgery, 53% had disease >10 years, mean fiber intake 16 g/d, 22% with flare at follow-up assessment, 6% on steroids, 65% on immunosuppressants, 69% on aminosalicylates and 68% on biologicals), and 489 had ulcerative colitis — UC (31% male, 4% had surgery, 43% had disease >10 years, mean fiber intake 18 g/d, 28% with flare at follow-up assessment, 5% on steroids, 64% on immunosuppressants, 85% on aminosalicylates and 55% on biologicals)

Results:

  • Those with ulcerative colitis were 2.6x more likely to be in the upper quartile of fiber intake, vs those with Crohn’s: OR 2.63 (1.91-3.62). The mean fiber intake in the upper quartile of those with Crohn’s was 23.7 g/d, and with ulcerative colitis was 24.5 g/d.
  • ​Men were about 5x more likely than women to be high fiber consumers: OR 4.74 (3.34-6.73)
  • Crohn’s disease
    • Comparing those on the highest to lowest fiber intake quartile, OR for having flare was 0.58 (0.37-0.90), a 42% decrease
    • Comparing the top decile to the bottom one: here was an even more pronounced effect size: OR 0.37 (0.16-0.85), or a 63% decrease
    • ​Overall results were similar if looking at whole grain consumption as part of the fiber
  • Ulcerative Colitis
    • ​No association between fiber intake and flares of UC
    • ​Though if look at the top vs the bottom decile of fiber consumption, there was a significant increase in flares with OR 4.78 (1.05-21.66) in those consuming more fiber [note the wide confidence intervals, which may reflect the smaller numbers of patients, making the point estimates unreliable; also, of unclear significance, those with UC tended to eat more fiber overall than those with CD]

So, a few issues:

  • Inflammatory bowel disease is associated with an abnormal mucosal immune response to commensal bacteria in the gut. And several studies in people without IBD have found that a high dietary fiber intake changes the gut microbiome, increasing short-chain fatty acids and butyrate production (butyrate has the positive effect of inhibiting inflammation, carcinogenesis and oxidative stress in the gut), which could conceivably help people with IBD (see  http://blogs.bmj.com/ebm/category/microbiome/ for some prior blogs on the microbiome)
  • But, though the data on fiber’s role has never been very clear, it is frequent that patients with IBD are told to limit their dietary intake of fiber [though, interesting in this study that those with CD reported eating a mean of 16 g/d, those with ulcerative colitis 18g/d, and these are pretty much the same as in the general population of 17 g/d per the National Health and Nutrition Examination Survey of 2009-10]. My understanding is that many people are afraid of the high fiber diet bulk in patients with CD and strictures, and that different patients are pretty different in what diets work best for them. There are several epidemiological studies, however, suggesting that a high fiber diet is helpful in preventing the development of CD.
  • It was also notable that the trend in UC was to more flares in those on higher fiber diets; and when looking at deciles of fiber intake, the increase was actually statistically significant. The concern in UC about fiber in some ways is less than with CD, since there are fewer strictures. Yet those with UC ate more fiber and had a higher propensity to flares.
  • This study was nonrandomized, creating significant room for bias. For example, maybe those people who elected to have a higher fiber diet were different from those who chose a low fiber diet? Maybe they had less severe disease in some ways than those having lower fiber intake (e.g., maybe those on a lower fiber diet had worse disease, more strictures and were afraid of obstruction): so perhaps there was a preselection bias of those with less bad disease eating more fiber?? The researchers did note that those on lower fiber diet tended to have longer duration of disease, past history of surgery, or past hospitalization for IBD, which suggests that there may have been a bias.
  • There was a systematic review of the role of fiber in patients with IBD (see Inflamm Bowel Dis. 2014 Mar;20(3):576), which assessed 23 RCTs (10 with CD and 12 with UC) and 1296 patients, finding that in UC 3/10 studies supported fiber supplementation but 0/12 in those with CD, though several studies did find improvement in GI symptoms and favorable changes in the microbiome with fiber. Although they were not specific clinical endpoints in the studies designs, several studies also found improvements in disease activity within the fiber group. Notably, there was no negative effect of high fiber diet in those with acute disease, either with UC or CD, and one showed positive effect in those with UC. Of note, these studies were so different in design that they could not do a meta-analysis.
  • So, given the potentially positive effects of a higher fiber diet (positive changes in microbiome, perhaps fewer flares), and in light of the systematic review not finding harm and perhaps some benefit of a higher fiber diet, it might be reasonable to try it. And, as noted above, there does seem to be a lot of individual variation in response to different diets, so any changes should be done with careful follow-up. But, this systematic review, contrary to much of the prevailing wisdom, did support higher fiber diets even during flares (i.e., no negative effects and some positive in those with UC). And it would be great to have a well-conducted, large RCT to really answer the question.
  • The reason I reviewed this study is that I manage a few patients with IBD, the dietary suggestions for IBD had mostly been against a higher fiber diet during flares, and the microbiome changes of high fiber diet seem so positive. I would still be hesitant to recommend this in a patient with CD and strictures, for fear that the combination of increased bowel wall inflammation and increased dietary bulk might not be so great. And some patients may feel worse (there can be more gas and potentially uncomfortable colonic distention with high fiber). But it may be worth a try.

Primary Care Corner with Geoffrey Modest MD: Antibiotics for Ulcerative Colitis??

17 Jun, 14 | by EBM

there has been ongoing speculation that there is a bacterial cause of ulcerative colitis (UC). Fusobacterium varium, in a prior study by the same researchers below, was found in actively inflamed colonic mucosa of patients with UC. (also, in mice, butyric acid, a byproduct of F. varium, causes UC-like lesions). so, this group devised an antibiotic cocktail active against F. varium (tid regimen of amoxacillin 500mg, tetracycline 500mg, and metronidazole 250mg for 2 weeks) and assessed its efficacy both in 30 patients with steroid-refractory and 64 patients with steroid-dependent active UC (see doi:10.1111/apt.12688).  primary endpoint was clinical response at 3 months after treatment completion. secondary endpoints were significant clinical and endoscopic score improvement at 12 months. results:

–Japanese multi-center non-randomized study. mean age 40. in steroid-dependent group, 45 males/19 females. pretty even in steroid-refractory group. extensive disease (70% of colon), mostly moderate severity. routine use of UC meds: sulfasalazine, 5-aminosalicylic acid, pred, azathioprine, 6-MP, mesalazine and/or probiotics — though <10% on azathiprine or mercaptorpurine. in steroid-dependent group, the steroid dose was tapered during the study — after week 8 by 5 mg/week until 20 mg dose. then decreased 2.5 mg/week til off.

–19 of 30 (63.3%) steroid-refractory and 47 of 64 (73.4%) of steroid-dependent had clinical resp in 2 weeks
–at 3 months, 60% of steroid-refractory and 56.3% of steroid-dependent achieved clinical remission
–at 12 months, 66.6% of steroid-refractory and 51.6% of steroid-dependent achieved clinical remission
–endoscopic activity scores paralleled the clinical activity scores
–in group with severe disease (16 pts), 80% with clinical response and 55% with clinical remission at 2 weeks, 3 and 12 months.
–in steroid-responsive group, 39 of 64 (60.9%) were able to stop steroids completely and remained in remission for 3 months
–the colectomy rate was 10% in steroid-refractory UC, less than reported rates with infliximab therapy

so, pretty impressive numbers. small study without control group, but cheap and easy treatment. also, Japanese study, so not sure the colonic microbiome is the same as here. but overall this study reminds me of a similar type study in the lancet around 20 years ago, finding that in a small number of patients with severe ITP and found to have H. pylori, H. pylori treatment led to dramatic remission of their ITP.  i happened to see someone around that time with ITP and severe ecchymoses, only marginally responsive to high dose prednisione, found to have H pylori antibody, treated for that and had a complete response within a month, and no recurrence since then….. so, these small research studies can be useful.

geoff

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