Introduction

Crohn’s disease (CD) is an inflammatory bowel disease (IBD) characterized by chronic inflammation and dysbiosis. Current pharmacologic-based treatment strategies have improved the course of CD but adverse effects and resistance call for exploring non-pharmacologic options. Diet plays a pivotal role in the development and progression of CD and recent studies highlight the feasibility and effectiveness of specific diet interventions in improving CD symptoms. However, little is known about the degree to which diet-modulation impacts biological responses in CD. To that end, we conducted a patient preference study to test a low fat, high fiber (LF/HF) diet in CD patients.

Aims & Methods

Here, we used unbiased serum proteomic screening to interrogate the systemic impact of short-term (8-week) catered dietary intervention on circulating protein levels in CD patients and healthy household controls (HHC) receiving identical diets. Serum samples were obtained from 10 CD patients and matched HHC enrolled in our LF/HF catered diet intervention study (NCT04213729) at baseline and 8-weeks following the diet. Quantitative proteome analysis was done using the SOMAscan assay (SomaLogic). Biological pathway and network analyses were performed.

Results

At baselined, CD patients had increased levels of the pro-inflammatory proteins serum amyloid A-1 (SAA1) and C-reactive protein (CRP) and increased levels of fibrinogen and Fibrinogen-like protein 1 (FGL1) compared with HHC. The immunomodulatory proteins C-type lectin domain family 12 member A (CLEC12A) and immunoglobulin A (IgA) were also elevated in CD patients compared to HHCs. In the same comparison, CD patients had reduced levels of Transcobalamin-2 (TCN2), the protein responsible for B-12 transport, and Alcohol dehydrogenase 1C (ADH1C), a protein recently highlighted for its immune-regulating role in IBD. After 8 weeks of catered LF/HF diet, CD patients had marked decrease of CRP, fibrinogen, FGL1, CLEC12A and an upregulation in ADH1C. In both CD patients and HHC, our data at the 8-week timepoint compared to baseline show a significant downregulation in the adipocyte-derived protein leptin and the Complement component 1 Q subcomponent-binding protein (C1QBP) which plays a role in impairing goblet cell formation IBD. We also observed a marked downward trend in the levels of SAA1 and CRP at the 8-week time point in CD patients and an upregulation in Ras-related protein (Rab-21) and (Rab-7), which are important in intestinal epithelium maintenance. Lastly, pathway analysis revealed a significant enrichment in pathways associated with amino acid and fatty acid metabolism, endothelial cell development, and cellular response to DNA damage following 8 weeks of LF/HF diet intervention in CD patients.

Conclusion

Overall, our results suggest that catering a diet high in fiber and low in fat for 8 weeks is enough to lead to distinct protein level modulations suggestive of improved immune function, mucosal healing, and inflammatory status. These strategies can lead to identification of novel targets of diet responses in CD.

Disclosure

NA

Introduction

The gut microbiota plays a crucial role in the pathogenesis and progression of Crohn’s Disease (CD) by maintaining intestinal homeostasis, supporting metabolic and immune functions, and influencing overall health. An imbalance in the gut microbiota is associated with CD, as disruptions in microbial composition can be further impacted by dietary factors, highlighting the connection between nutrition and gut health.

Aims & Methods

This study aimed to evaluate the gut microbiota composition and its interactions with dietary factors to identify potential opportunities for targeted probiotic interventions in CD management. The study included 53 participants, of whom 20 had CD in remission, 18 had active disease, and 15 were healthy controls. CD activity was evaluated by colonoscopy assessment or by nuclear magnetic resonance scan enterography. All participants aged between 18 and 60 years were assessed using 24-hour dietary recall and gut microbiome profiling through 16S rRNA gene sequencing. Patients had confirmed diagnoses of CD with ileal and/or colonic involvement. The local ethics committee approved this study.

Results

Microbial composition analyses (beta diversity) revealed significant differences between groups. At the Operational Taxonomic Unit (OTU) level, healthy microbiome differed significantly from both remission and active CD patients, with healthy controls showing a more similar microbial composition compared to remission (p = 0.001) and active disease (p = 0.001). In addition, Shannon diversity analyses demonstrated that healthy individuals exhibited significantly higher OTU diversity compared to CD patients, further highlighting the microbial imbalance associated with the disease. Among specific taxa, Eubacterium hallii, a key butyrate producer, was significantly reduced in patients with active CD. This microorganism is integral to intestinal metabolic balance, playing essential roles in energy homeostasis, colonic motility, immunomodulation, and inflammation suppression. Furthermore, E. hallii plays a critical role in bile acid and cholesterol metabolism, highlighting its importance in gut health. Disease severity was associated with changes in microbial abundance, with specific taxa colonizing the gut at higher levels as disease activity increased, including Escherichia coli, Escherichia-Shigella, and taxa from the Enterobacteriaceae, Lachnospirales, and Bacteroides. This growth may be linked to inflammatory processes and intestinal dysbiosis, suggesting a potentially pathogenic role. Furthermore, dietary components such as saccharin, an artificial sweetener, were significantly associated with alterations in microbial composition.

Conclusion

These findings underline the potential for probiotics targeting specific taxa, such as E. hallii, to restore microbial balance and improve clinical outcomes in CD. The study also highlights the impact of dietary components, such as saccharin, in disrupting the gut microbiome, suggesting that certain dietary factors may contribute to microbial imbalance and inflammation in CD. Future research should focus on integrating dietary patterns with probiotic development to optimize gut health and mitigate inflammation in CD patients.

References

1. BOLTE, L. A. et al. Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome. Gut, p. gutjnl-2020-322670, 2 abr. 2021.
2. FAN, Y.; PEDERSEN, O. Gut microbiota in human metabolic health and disease. Nature Reviews Microbiology, v. 19, n. 1, p. 55–71, 4 jan. 2021.
3. GILL, P. A. et al. The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease. Frontiers in Immunology, v. 13, n. April, p. 1–22, 5 abr. 2022.

Introduction

Crohn’s disease (CD) can lead to inflammation of the intestinal tract and may be complicated by strictures¹. Patients want diet-based approaches to therapy but relatively few prospective diet studies have been conducted with high rates of adherence.

Aims & Methods

We conducted a patient preference study NCT04213729 to test a high fiber(17gm/1000 calories for fiber), low fat(20-25% calories from fat) diet in CD patients. In the current study, we asked whether patients changed their symptoms following the catered diet intervention and whether the CD-related phenotype impacted the response to diet. Patients chose to receive diet counseling alone (group 1), catered food for 8 weeks (group 2), or catered food for a patient and a household member as well as participate in Dyadic Psychosocial Support (DPS)sessions (group 3).DPS sessions incorporated psychoeducational components that combined didactic and behavioral procedures. High fiber catered foods consisted of soluble and insoluble fibers as well as fermentable fibers such as fructans and galactooligosaccharides, etc. Detailed demographic, clinical, anthropomorphic, quality of life, biochemical and food knowledge data were collected at baseline and week 8. A total of 73 patients and 24 household controls were enrolled.

Results

At baseline,60-80%of CD patients were in remission based on PRO2 score (stool frequency≤ 1.5, abdominal pain ≤1)and Harvey Bradshaw index<5. On average, CD patients consumed a diet with less than 9gm/1000 calories of fiber and >40% fat at baseline. All three CD groups were well-matched at baseline with the household controls consuming also less fiber. Patients receiving the catered food had a high rate of adherence to the diet(80%)at week 8; patients receiving diet counseling alone had 5%adherence to a low-fat diet and 10%adherence to a high-fiber diet at week 8. Serum amyloid A(SSA), CRP, and fecal calprotectin were low at baseline and remained low. Catered meals improved values of fecal calprotectin or SAA in the subset of patients that had elevated levels of these biomarkers. Group 3 received DPS sessions for the CD patient and household control and had significantly improved nutrition literacy (score average:70.6,p=0.000636)while groups 1 and 2 averaged 57 and 57.1, respectively. Food-related quality of life(FRQoL 29)scores were significantly improved for those participants that received diet and DPS. FRQoL average increased from 82.1 to 107(p=0.000541).29% had B2 fibro-stenotic disease and received high-fiber catered food. This subset of patients had a decrease in stool frequency and no increase in abdominal pain symptoms. The mean number of bowel movements and pain scores improved or did not change.

Conclusion

CD patients even those in remission, have very low consumption of fruits and vegetables. We show that even patients with B2 phenotype CD can tolerate 8 weeks of high fiber, low-fat diet without worsening of symptoms. One time diet counseling was not able to change diet behavior. Catering meals offers an effective way to control dietary intake in CD clinical trials. Psychology interventions for the CD patient and household improved food-related quality of life and nutritional literacy.

References

1. Rieder F, Zimmermann EM, Remzi FH, Sandborn WJ. Crohn's disease complicated by strictures: a systematic review. Gut. 2013 Jul;62(7):1072-84. doi: 10.1136/gutjnl-2012-304353. Epub 2013 Apr 26. PMID: 23626373; PMCID: PMC4884453.

Introduction

Crohn’s disease (CD) is characterized by chronic intestinal inflammation due to genetic and environmental factors. Microbiome studies have consistently shown dysbiosis in patients with CD. Diet is an important risk factor in the development of CD and may contribute to changes in the gut microbiota (GM). We conducted a prospective diet intervention study in CD patients and compared one time diet counseling versus catered meals that were high fiber (17g/1000 calories) and low fat (20-25% calories from fat) for 8 weeks (w) and followed for a total of 36w.

Aims & Methods

We hypothesized that metaproteomic characterization of the GM in CD in the context of dietary manipulation could edify response to diet intervention therapy. Patients chose to receive diet counseling alone (group 1), catered food for 8 weeks (group 2), or catered food for a patient (group 3P) and a household control (HHC) (group 3C) as well as participate in Dyadic Psychosocial Support (DPS) sessions (group 3P and 3C). A total of 70 patients and 22 HHC were followed prospectively and collected stool at baseline, week 8, and week 36. Samples were processed with a proven pipeline to isolate and digest bacterial proteins to perform LC-MS analysis.¹ Samples with bacterial protein groups lower than 1800 were not included for further analysis. The resulting dataset was processed with the MetaLab 2.3 application to build a sample specific database (SS-DB) from the integrated gene catalog (IGC)-DB.² Taxonomic assignment to identify peptides was performed using the Unipept desktop version.³

Results

The average taxon-specific peptide distribution in the GM, especially at less specific taxonomic levels, did not show a striking difference between the groups at baseline. At the species level, after 8 weeks of a catered diet there was a general reduction of Collinsella aerofaciens that was more marked in groups 2 and 3P than in the HHC in group 3C. Collinsella aerofaciens has been linked to TLR2 activation, pro-inflammatory responses, and CD.⁴ We also observed a continuous increase in Prevotella copri over time in CD patients ultimately resulting in similar patterns as seen in the household controls. P. copri has recently been recognized as an important biomarker for diet improvements in dysbiosis⁵. In particular, there was an increase of proteins associated with carbohydrate metabolic processes in P. copri in the CD patients over time. Large scale annotation of the metaproteins and their related functions is ongoing.

Conclusion

Evidence suggests that a catered high fiber, low fat diet induces a change in the GM of CD patients more than in healthy subjects. The ability to compare the effect of a diet intervention in CD patients versus matched household controls will give additional power to understanding how diet can be used to manipulate the microbiome in the context of dysbiosis.

References

1) Levi Mortera et al. - International Journal of Molecular Science (2022) 23 (24), 15982; 2) Cheng et al. – Microbiome (2017), 5 (1), 157; 3) Verschaffelt et al. – Journal of Proteome Research (2021), 20 (4), 2083-2088; 4) Kwon J. et al. J Am Chem Soc. 2023 Apr 5; 145(13): 7071–7074; 5) Precup & Vodnar - British Journal of Nutrition (2019), 122, 131-140

Clinical Case Summary

Background: Protein-energy malnutrition (PEM) is a common complication in patients with Crohn’s disease (CD), affecting 30% to 82.8% of individuals. Contributing factors include diarrhea, inflammatory activity, dietary restrictions, and nutrient malabsorption. This case report aims to describe a newly diagnosed CD patient with severe malnutrition and myopenia, highlighting the impact of inflammatory activity on nutritional status and the importance of early multidisciplinary management for optimizing treatment and improving quality of life.
Case report: A 27-year-old female patient presented with abdominal pain, anorexia, and progressive weight loss of 10 kg over five months (22% of body weight), consistent with severe malnutrition. She was admitted to diagnostic evaluation, and complementary exams confirmed a diagnosis of CD with ileal involvement, stenosing type (Montreal A2L1B2). Treatment was initiated with combined infliximab and azathioprine therapy. Nutritional assessment revealed a weight of 31 kg, BMI of 12.3 kg/m² (severe underweight), phase angle of 4.4°, lean mass of 26.1 kg, and fat mass of 4.9 kg, with an abnormal intra/extracellular mass ratio (0.75). The patient was classified as severely malnourished based on arm muscle circumference (AMC), with both lean and fat mass below expected levels. Computed tomography (CT) showed a muscle area of 82.02 cm², visceral fat of 1.80 cm², and subcutaneous fat of 1.49 cm², with a Skeletal Muscle Index (SMI) of 32.44 cm²/m² (reference range: 38.5 cm²/m²), indicating myopenia.
Conclusion: Myopenia is a common condition in CD patients and is associated with worsened quality of life, increased risk of disease relapse, and therapeutic failure. The inflammatory process exacerbates malnutrition through anorexigenic mediators, while muscle mass reduction underscores the need for studies focusing on nutrition and physical exercise as complementary strategies in the management of inflammatory bowel diseases.

References

• Balestrieri, P., Ribolsi, M., Guarino, M. P. L., Emerenziani, S., Altomare, A., & Cicala, M. (2020). Nutritional Aspects in Inflammatory Bowel Diseases. Nutrients, 12(2), 372. https://doi.org/10.3390/nu12020372
• Wei, H., Yuan, Z., Ren, K., Jin, Y., Ren, L., Cao, B., Zhou, Y., & Chen, L. (2023). Body Composition in Inflammatory Bowel Disease. Archives of Iranian medicine, 26(3), 172–175. https://doi.org/10.34172/aim.2023.26
• Massironi, S., Viganò, C., Palermo, A., Pirola, L., Mulinacci, G., Allocca, M., Peyrin-Biroulet, L., & Danese, S. (2023). Inflammation and malnutrition in inflammatory bowel disease. The lancet. Gastroenterology & hepatology, 8(6), 579–590. https://doi.org/10.1016/S2468-1253(23)00011-0
• Ando, K., Uehara, K., Sugiyama, Y., Kobayashi, Y., Murakami, Y., Sato, H., Kunogi, T., Sasaki, T., Takahashi, K., Ueno, N., Kashima, S., Moriichi, K., Tanabe, H., Okumura, T., & Fujiya, M. (2022). Correlation Among Body Composition Parameters and Long-Term Outcomes in Crohn's Disease After Anti-TNF Therapy. Frontiers in nutrition, 9, 765209. https://doi.org/10.3389/fnut.2022.765209
• Nardone, O. M., de Sire, R., Petito, V., Testa, A., Villani, G., Scaldaferri, F., & Castiglione, F. (2021). Inflammatory Bowel Diseases and Sarcopenia: The Role of Inflammation and Gut Microbiota in the Development of Muscle Failure. Frontiers in immunology, 12, 694217. https://doi.org/10.3389/fimmu.2021.694217