scholarly journals Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

2020 ◽  
Vol 9 (8) ◽  
pp. 2448
Author(s):  
Carolina Serena ◽  
Maribel Queipo-Ortuño ◽  
Monica Millan ◽  
Lidia Sanchez-Alcoholado ◽  
Aleidis Caro ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Pathogenic Bacteria ◽  
Sulfur Metabolism ◽  
Clinical Status ◽  
Subcutaneous Fat ◽  
Intestinal Barrier ◽  
Fecal Calprotectin ◽  
Inactive Disease

Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.

scholarly journals Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat

2021 ◽  
Vol 22 (8) ◽  
pp. 4292
Author(s):  
Ana Madeira ◽  
Carolina Serena ◽  
Miriam Ejarque ◽  
Elsa Maymó-Masip ◽  
Monica Millan ◽  
...  
Keyword(s):  
Immune Response ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wilms Tumor ◽  
Expression Profiles ◽  
Subcutaneous Fat ◽  
Hla Dr ◽  
Wide Range ◽  
Antigen Presenting

Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn’s disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn’s disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms’ tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn’s disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen—DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn’s disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn’s disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn’s disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.

scholarly journals Visceral Adipose Tissue Is Associated With Stricturing Crohn’s Disease Behavior, Fecal Calprotectin, and Quality of Life

2018 ◽  
Vol 25 (3) ◽  
pp. 592-600 ◽  
Author(s):  
Robert Venning Bryant ◽  
Christopher G Schultz ◽  
Soong Ooi ◽  
Charlotte Goess ◽  
Samuel Paul Costello ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Visceral Adipose Tissue ◽  
Fecal Calprotectin ◽  
Disease Behavior ◽  
Visceral Adipose

scholarly journals P001 Succinate, a gut microbiota-derived metabolite, modulates the inflammatory status of the creeping fat in Crohn’s disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S123-S123
Author(s):  
C Serena ◽  
D Monfort-Ferre ◽  
M Bautista ◽  
M Menacho ◽  
M Martí ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Response ◽  
Intestinal Barrier ◽  
Fine Tuning ◽  
Clinical Activity ◽  
Faecal Calprotectin ◽  
Inflammatory Status ◽  
Adipose Tissue Dysfunction

Abstract Background Crohn’s disease [CD] is characterized by severe transmural inflammation with subsequent destruction of the intestinal barrier. Recent works suggest that bacterial infiltration across this leaky gut facilitates access to the mesenteric fat and the development of a subsequent inflammatory reaction in the surrounding adipose tissue named creeping fat [CF]. Dysbiosis in CD patients has been associated with an increase in succinate-producing bacteria and a decrease in succinate-consuming bacteria. In fact, elevated succinate levels have been found in the intestinal and faeces of CD patients. Succinate has been classically considered as a marker of hypoxia and tissue damage, assisting as a pro-inflammatory signal that triggers immune activation. However, recent observations support potential additional functions of succinate. We and others have shown that succinate plays a key role in fine-tuning of the inflammatory response, acting both as an alarmin and resolving molecule. Our hypothesis is that succinate, a microbiota-derived metabolite, is a new determinant of adipose tissue dysfunction in CD. Methods A well-characterized cohort was used to obtained mesenteric adipose tissue biopsies including a) 10 subjects with active CD that require surgery for their underlying pathology b) 10 subjects with inactive CD and c) 10 healthy controls undergoing surgery for non-acute process (herniorrhaphy, cholecystectomy for lithiasis, etc.). The groups were comparable in age, sex, and body mass index. We studied the effect of exogenous succinate in adipose tissue explants, adipose-stem cells (ASC), and adipose tissue macrophages (ATM) isolated from adipose tissue biopsies of CD patients with different clinical activity. Circulating succinate levels and inflammatory variables including hs-CRP and faecal calprotectin were also measured. Results We observed an increased expression of SUCNR1 in CF, including ASCs and ATMs, mainly in patients suffering from an active disease (figure 1A). Furthermore, succinate appears to elicit a different response in adipose tissue from CD patients, when activity status is considered. Thus, our results indicate that in an inflammatory local and systemic environment, such as occurs in CD active patients, succinate triggers a pro-inflammatory response in VAT depot, while when subjects are in a remission period, the response of VAT explants to succinate is similar to than the observed in healthy subjects, promoting an anti-inflammatory expression profile (Figure 1B). Interestingly, we found elevated circulating succinate levels in active CD patients but those decrease drastically in patients in remission of the disease (Figure 1C). Conclusion Succinate has a relevant role in adipose tissue dysfunction in CD.

scholarly journals Authors’ reply: The Association Between Visceral Adipose Tissue and Stricturing Crohn’s Disease Behavior, Fecal Calprotectin and Quality of Life

2018 ◽  
Vol 25 (6) ◽  
pp. e62-e63
Author(s):  
Robert Venning Bryant ◽  
Christopher G Schultz ◽  
Soong Ooi ◽  
Charlotte Goess ◽  
Samuel Paul Costello ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Visceral Adipose Tissue ◽  
Fecal Calprotectin ◽  
Disease Behavior ◽  
Visceral Adipose

scholarly journals DOP84 Crohn’s disease modifies the DNA methylome of human adipose-stem cells, which is only partially re-established in remission

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S123-S125
Author(s):  
C Serena ◽  
M Millan ◽  
M Ejarque ◽  
A Saera-Vila ◽  
D Monfort-Ferré ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Association Studies ◽  
Subcutaneous Fat ◽  
Human Adipose Tissue ◽  
Phagocytic Capacity ◽  
Inflammatory Profile ◽  
The Impact

Abstract Background Crohn’s disease (CD) is characterised by the expansion of mesenteric adipose tissue, termed creeping fat (CF). We previously demonstrated that human adipose-tissue stem cells (hASCs) from CF exhibit a dysfunctional phenotype, including a pro-inflammatory profile, high phagocytic capacity and weak immunosuppressive properties. Importantly, these phenotypes persist in patients in remission, and are found in all adipose depots explored including subcutaneous fat. We hypothesised that this is a consequence of epigenetic modifications. Methods Epigenome-wide association studies using the 850k EPIC Illumina array were used to explore the impact of CD on the methylation signature of hASCs isolated from the subcutaneous fat (Figure 1). Changes in the expression of differentially methylated candidate genes were validated in hASCs of patients with active/inactive CD and healthy controls (Figure 1). Conclusion hASCs of patients with CD exhibit an alter DNA-methylation and gene expression profile. Remarkably, the expression of several genes is only partially restored in patients with inactive CD. Understanding how CD shapes the functionality of hASCs is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies.

scholarly journals Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

2021 ◽  
Author(s):  
Shinichiro Shinzaki ◽  
Katsuyoshi Matsuoka ◽  
Hiroki Tanaka ◽  
Fuminao Takeshima ◽  
Shingo Kato ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Potential Biomarker ◽  
Adalimumab Therapy ◽  
Adalimumab Treatment ◽  
Inflammatory Bowel

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

scholarly journals Bacterial gut dysbiosis is associated with Crohn’s disease symptoms but not with elevated fecal calprotectin

2021 ◽  
pp. 101669
Author(s):  
Sylvie Buffet-Bataillon ◽  
Clémence Landreau ◽  
Laurent Siproudhis ◽  
Vincent Cattoir ◽  
Guillaume Bouguen
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Fecal Calprotectin ◽  
Disease Symptoms ◽  
Gut Dysbiosis

Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease

2021 ◽  
Vol 44 (2) ◽  
pp. 87-95
Author(s):  
Francisco Guilherme Cancela Penna ◽  
Rodrigo Macedo Rosa ◽  
Fernando H. Pereira ◽  
Pedro Ferrari Sales Cunha ◽  
Stella Cristina S. Sousa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Therapeutic Target ◽  
Fecal Calprotectin ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Combined Evaluation
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