Diet-microbiome links drive IBD inflammation
Advanced genetic testing of gut bacteria shows certain microbes and their byproducts may help lower inflammation in Crohn’s disease and ulcerative colitis.
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02/23/2026
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by Doug Brunk
In a study that followed 198 adults over time, better diet quality was linked to lower inflammation in people with inflammatory bowel disease (IBD).
However, the analysis showed that the gut microbiome played different roles in Crohn’s disease (CD) compared with ulcerative colitis (UC).
In the study from Spanish investigators published in Gut, 49 patients with CD, 49 with UC, and 100 healthy controls completed a validated 58-item food frequency questionnaire and provided stool samples at baseline and 6 months.
The researchers used shotgun metagenomic sequencing to identify which microbes were present and what functions they could perform. To assess clinical activity, they used the Harvey-Bradshaw Index (HBI) for CD and the Colitis Activity Index (CAI) for UC, and measured C-reactive protein (CRP) and fecal calprotectin in both groups of patients. Causal mediation analyses adjusted for age, sex, body mass index, smoking, infliximab, mesalazine, and recent antibiotic use.
Dietary profiles differed significantly between IBD and HCs at the level of food items, food groups, and macronutrients (Permutational Multivariate Analysis of Variance [PERMANOVA] q=0.0015 for all), with CD and UC clustering more tightly than HCs. Both IBD groups reported lower intake of vegetables, fruits, nuts/seeds, and fiber, alongside lower scores on the Alternative Mediterranean Diet (aMED), Healthy Eating Index–2015 (HEI-2015), Índice de Alimentación Saludable (IASE), the Healthy Food Diversity Index (HFD-Index), Mean Adequacy Ratio (MAR), and healthful Plant-Based Diet Index (hPDI). CD patients also had reduced carbohydrate and protein intake.
Microbial diversity followed a disease gradient: lowest in CD, intermediate in UC, highest in HCs (Chao1 and Shannon indices; P<.05 for pairwise comparisons). Dysbiosis scores were highest in CD. Alpha diversity correlated inversely with CRP and bowel frequency, while dysbiosis correlated positively. Higher aMED, HEI-2015, hPDI, and MAR scores were associated with greater diversity and lower dysbiosis.
The investigators found that, overall, people’s usual fiber intake was not linked to levels of CRP, calprotectin, or overall disease activity. The only exception was a small link in people with Crohn’s disease (CD): higher fiber intake was related to slightly lower HBI scores (Spearman ρ = –0.23; P = .049). They also found no meaningful differences in diet between people in relapse and those in remission. Changes in diet over six months were not linked to changes in inflammatory markers.
In CD, healthier dietary indices, coffee, and whole wheat bread were associated with lower HBI, but not via global diversity metrics. Instead, taxon-specific mediation was observed. Higher HEI-2015 and MAR scores and coffee intake were linked to lower HBI through increased relative abundance of Bacteroides caccae, Bacteroides faecis, and Bacteroides thetaiotaomicron, relative to Bacteroides fragilis. Whole wheat bread intake was mediated by increased Butyricimonas paravirosa, Butyricimonas faecihominis, and Odoribacter splanchnicus and decreased Coprobacter fastidiosus. Coffee intake was also associated with lower calprotectin via increased Lawsonibacter asaccharolyticus and reduced Clostridiales bacterium.
Functional mediation analyses showed that short-chain fatty acid (SCFA) pathways play an important role. In CD, nearly one-third of coffee’s overall effect on the Harvey–Bradshaw Index (HBI) was explained by a pathway that ferments hexitols into acetate. Soft drink intake was linked to higher HBI scores, and more than 80% of this effect was explained by a mixed-acid fermentation pathway.
In UC, most of the effects were explained by overall changes in the gut microbiome. Higher unhealthy Plant-Based Diet Index (uPDI) scores were linked to higher levels of CRP and calprotectin. This was partly because these diets were associated with lower microbial diversity and more dysbiosis. Higher aMED scores were linked to lower CRP and calprotectin levels, mainly through reduced dysbiosis. About 60% of aMED’s anti-inflammatory effect on CRP was explained by an acetate-related pathway called acetylene degradation. Fruit, coffee, and olive oil intake showed similar patterns, with their effects linked to greater microbial diversity and less dysbiosis.
The researchers acknowledged limitations of their study, including reliance on self-reported diet and treatment of repeated measures as independent observations. “In UC, diet appears to modulate inflammation primarily through restoration of microbial diversity and functional balance, whereas in CD, selective modulation of specific taxa and metabolic pathways may play a dominant role,” they wrote. “These findings underscore the potential of personalized, microbiome-informed dietary strategies as complementary tools for precision management of IBD.”
The study was funded by the Instituto de Salud Carlos III and co-funded by the European Union and the Spanish Ministry of Economy and Competitiveness. Additional support came from the Fondo Europeo de Desarrollo Regional and the Agency for Management of University and Research Grants.
Summary content
7 Key Takeaways
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The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.