Mesenteric Bacterial Translocation in Evolved Crohn's Disease

Crohn Disease Clinical Trial

— MESENCROHN  

Official title:

Mesenteric Bacterial Translocation in Evolved Crohn's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05891756
• Other study ID #: MESENCROHN
• Status: Recruiting
• Start date: July 1, 2022
• Est. completion date: December 2025

Study information

• Verified date: June 2023
• Source: Hospital Mutua de Terrassa
• Contact: Yamile Zabana, MD, PhD
• Email: yzabana[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Mesenteric fat can be invaded by gut bacteria through a process called bacterial translocation, which is the invasion of viable bacteria from the gastrointestinal tract to extraintestinal sites (mesenteric lymph nodes, liver, spleen, kidney, bloodstream, etc.). In Crohn's disease (CD), bacterial translocation could increase the disproportionate inflammatory response already present and contribute to disease progression by stimulating the production of pro-inflammatory cytokines and immune-cell infiltration in the mesentery. Several mechanisms may promote bacterial translocation, such as bacterial overgrowth, disruption of the intestinal mucosal barrier and alterations in the immune system.

Ileocecal surgical resection is required in some patients with complicated or refractory CD. Unfortunately, post-surgical disease recurrence happens in up to 40% of cases, probably defining a subgroup of CD patients with a particular aggressive form of the disease. The complete microbiome (in gastrointestinal and extraintestinal sites) in CD patients that develop early post-surgical recurrence, as well as the association to innate immunity alterations, has not yet been studied.

The primary aim of the study is to explore the bacterial microbiome of CD patients and its association with early post-surgical recurrence and clinical or genetic variables related to innate immunity. To achieve this, the bacterial DNA present in mesenteric fat and ileal tissue (inflamed and non-inflamed) from surgical resection samples as well as blood samples from CD patients will be studied. Genetic polymorphisms, relevant clinical data and disease recurrence will also be evaluated.

The investigators hypothesize that bacterial translocation to the mesentery fat near the inflamed intestine is one of the mechanisms for perpetuation and chronicity of inflammation and therefore post-surgical recurrence in CD. The investigators expect to find a distinctive bacterial profile (in quantity and quality) in the mesenteric fat of patients with early post-surgical recurrence and/or with genetic variants that cause alterations in innate immunity.

The study of the microbiome in CD could help to identify the patients with a more aggressive disease form that will probably present early post-surgical recurrence, and could raise the possibility of microbial modulation as therapy for CD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults (18 years or older)

• Informed consent signed

• To require an ileocecal resection as part of the treatment of Crohn's Disease

• In the case of controls: not having Inflammatory Bowel Disease and requiring an ileocecal resection for another reason

Exclusion Criteria:

• To require an ileocecal resection with definitive or transient ileostomy

• In the case of controls: existence of a family history of Inflammatory Bowel Disease.

Related Conditions & MeSH terms

• Crohn Disease

Locations

Country	Name	City	State
Spain	Hospital Universitari MútuaTerrassa	Terrassa	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Mutua de Terrassa

Country where clinical trial is conducted

Spain, 

References & Publications (15)

Alexander JW, Boyce ST, Babcock GF, Gianotti L, Peck MD, Dunn DL, Pyles T, Childress CP, Ash SK. The process of microbial translocation. Ann Surg. 1990 Oct;212(4):496-510; discussion 511-2. doi: 10.1097/00000658-199010000-00012. — View Citation

Batra A, Heimesaat MM, Bereswill S, Fischer A, Glauben R, Kunkel D, Scheffold A, Erben U, Kuhl A, Loddenkemper C, Lehr HA, Schumann M, Schulzke JD, Zeitz M, Siegmund B. Mesenteric fat - control site for bacterial translocation in colitis? Mucosal Immunol. 2012 Sep;5(5):580-91. doi: 10.1038/mi.2012.33. Epub 2012 May 9. — View Citation

Bertin B, Desreumaux P, Dubuquoy L. Obesity, visceral fat and Crohn's disease. Curr Opin Clin Nutr Metab Care. 2010 Sep;13(5):574-80. doi: 10.1097/MCO.0b013e32833cf0f4. — View Citation

Domenech E, Manosa M, Bernal I, Garcia-Planella E, Cabre E, Pinol M, Lorenzo-Zuniga V, Boix J, Gassull MA. Impact of azathioprine on the prevention of postoperative Crohn's disease recurrence: results of a prospective, observational, long-term follow-up study. Inflamm Bowel Dis. 2008 Apr;14(4):508-13. doi: 10.1002/ibd.20359. Erratum In: Inflamm Bowel Dis. 2008 Dec;14(12):1761. — View Citation

Gutierrez A, Scharl M, Sempere L, Holler E, Zapater P, Almenta I, Gonzalez-Navajas JM, Such J, Wiest R, Rogler G, Frances R. Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease. Gut. 2014 Feb;63(2):272-80. doi: 10.1136/gutjnl-2012-303557. Epub 2013 Feb 1. — View Citation

Kiernan MG, Coffey JC, McDermott K, Cotter PD, Cabrera-Rubio R, Kiely PA, Dunne CP. The Human Mesenteric Lymph Node Microbiome Differentiates Between Crohn's Disease and Ulcerative Colitis. J Crohns Colitis. 2019 Jan 1;13(1):58-66. doi: 10.1093/ecco-jcc/jjy136. — View Citation

Kosovac K, Brenmoehl J, Holler E, Falk W, Schoelmerich J, Hausmann M, Rogler G. Association of the NOD2 genotype with bacterial translocation via altered cell-cell contacts in Crohn's disease patients. Inflamm Bowel Dis. 2010 Aug;16(8):1311-21. doi: 10.1002/ibd.21223. — View Citation

Laffineur G, Lescut D, Vincent P, Quandalle P, Wurtz A, Colombel JF. [Bacterial translocation in Crohn disease]. Gastroenterol Clin Biol. 1992;16(10):777-81. French. — View Citation

Li Y, Zuo L, Zhu W, Gong J, Zhang W, Gu L, Guo Z, Li N, Li J. The impact of bacterial DNA translocation on early postoperative outcomes in Crohn's patients undergoing abdominal surgery. J Crohns Colitis. 2015 Mar;9(3):259-65. doi: 10.1093/ecco-jcc/jju029. Epub 2015 Jan 2. — View Citation

Schaffler A, Scholmerich J. Innate immunity and adipose tissue biology. Trends Immunol. 2010 Jun;31(6):228-35. doi: 10.1016/j.it.2010.03.001. — View Citation

Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006 Nov;116(11):3015-25. doi: 10.1172/JCI28898. Epub 2006 Oct 19. — View Citation

Siegmund B. Mesenteric fat in Crohn's disease: the hot spot of inflammation? Gut. 2012 Jan;61(1):3-5. doi: 10.1136/gutjnl-2011-301354. Epub 2011 Nov 7. No abstract available. — View Citation

Sokol H, Brot L, Stefanescu C, Auzolle C, Barnich N, Buisson A, Fumery M, Pariente B, Le Bourhis L, Treton X, Nancey S, Allez M, Seksik P; REMIND Study Group Investigators. Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn's disease. Gut. 2020 Mar;69(3):462-472. doi: 10.1136/gutjnl-2019-318719. Epub 2019 May 29. — View Citation

Takesue Y, Ohge H, Uemura K, Imamura Y, Murakami Y, Yokoyama T, Kakehashi M, Sueda T. Bacterial translocation in patients with Crohn's disease undergoing surgery. Dis Colon Rectum. 2002 Dec;45(12):1665-71. doi: 10.1007/s10350-004-7256-z. — View Citation

Zulian A, Cancello R, Micheletto G, Gentilini D, Gilardini L, Danelli P, Invitti C. Visceral adipocytes: old actors in obesity and new protagonists in Crohn's disease? Gut. 2012 Jan;61(1):86-94. doi: 10.1136/gutjnl-2011-300391. Epub 2011 Sep 19. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in the proportions and abundance of bacterial taxa (defined as total percentage of bacterial DNA sequences) between the mesentery, ileal tissue and blood between CD patients with and without early post-surgical disease recurrence		at inclusion (surgery)
Primary	Differences in the function of the bacterial profile (defined as the metagenome function analysis) between the mesentery, ileal tissue and blood between CD patients with and without early post-surgical disease recurrence		at inclusion (surgery)
Secondary	Association analysis of genetic variants related to innate immunity and the bacterial microbiome profile of CD patients	DNA polymorphisms detection in blood: ATG16L1 (rs2241880, rs3792109, rs3828309); NOD2 / CARD15 (rs2066844, rs2066845) and IRGM (rs13361189, rs4958847, rs1336119, rs10065172, rs7714584).	at inclusion (surgery)