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Edouard Louis

Publications and source records attributed to Edouard Louis.

15 recordsLinked to original sources
PubMed2026

Multi-level aggregation analysis of microbiome composition and host gene expression reveals associations with systemic and local immunity.

The human gut microbiome plays a critical role in immune regulation, yet the molecular links between microbiome composition and host gene expression remain incompletely understood. We analyzed associations between host gene expression and microbiome composition in a cohort of 315 healthy individuals, integrating microarray-based gene expression data from three intestinal sites (ileum, transverse colon, and rectum) and six immune cell types with microbiome sequencing data. Using a hierarchical feature aggregation strategy combining principal component analysis, clustering, and covariate correction, we discovered significant associations primarily related to immunity. While microbial profiles were similar across the three intestinal sites, the transverse colon yielded the most "microbiome-host gene expression" associations. Among the immune cell types, CD8+ cells showed the highest number of associations. The first principal component of microbiome composition, reflecting a gradient from commensals (e.g., Ruminococcaceae and Christensenellaceae) to proinflammatory taxa ([Ruminococcus] gnavus and Lachnoclostridium), correlated with the expression of TNF-α-linked genes (HMOX1, CPI17, HSD3B2, and SLC5A1). Among individual genera, Catenibacterium abundance was associated with gene expression in both intestinal and immune cells, including negative associations with MRPS21 (related to mitochondrial function) in the transverse colon and with CD8+ gene programs related to T cell differentiation. These findings align with emerging evidence implicating mitochondrial dysfunction in intestinal inflammation. Our results identify multi-level associations between the gut microbiome and host gene expression, suggesting potential mechanisms by which microbiota shape local and systemic immunity and vice versa. The implicated genes and taxa represent candidates for experimental validation to improve understanding of host-microbiome homeostasis and its disruption in disease.IMPORTANCEThe gut microbiome and immune system are engaged in a complex interplay throughout human life. While most associative studies focus on case-control comparisons-typically examining patients with conditions such as inflammatory bowel disease or metabolic diseases-less is known about the molecular links between the microbiome and immune system in healthy individuals. In this study of a large cohort of healthy individuals, we addressed this gap by applying multiscale modeling to tackle the high dimensionality of host-microbiome data. We identified multi-level associations between microbiome composition and host gene expression in both intestinal tissues and immune cells. These findings offer a valuable reference for understanding baseline host-microbiome communication and highlight molecular candidates-such as TNF-α-related genes and mitochondrial pathways-for future experimental validation.

Humans↗
PubMed2007

Multidrug resistance gene-1 polymorphisms and resistance to cyclosporine A in patients with steroid resistant ulcerative colitis.

BACKGROUND: Cyclosporine A (CsA) is inconstantly effective in inducing remission in acute attacks of ulcerative colitis (UC) not responding to steroids. This study aimed to establish whether multidrug resistance gene (MDR)1 polymorphisms would be associated with CsA failure. PATIENTS AND METHODS: The distribution of the different genotypes of single nucleotide polymorphisms (SNP) G2677T/A and C3435T of MDR1 exons 21 and 26, respectively, was studied in 154 patients (mean age, 44 yr) who had received CsA to treat severe attacks of steroid resistant UC in 11 centers in France and Belgium. Patients were classified as CsA failure (n = 50) when they needed colectomy within 30 days after CsA initiation. The SNPs were detected by use of a 5' nuclease allelic discrimination assay. RESULTS: There was a significant association between the G2677T/A polymorphism distribution (exon 21) and the risk for CsA failure (P = 0.0001). The TT genotype of exon 21 was significantly associated with the risk compared with the two other genotypes (odds ratio, 3.77; 95% confidence interval, 1.42-9.97, P = 0.007). There was no significant association between the genotype C3435T distribution (exon 26) and the risk of CsA failure (P = 0.23). CONCLUSION: The TT genotype of exon 21 MDR1 polymorphisms is associated with a higher risk of CsA failure in patients with steroid resistant UC. Further studies should be performed to establish whether other treatments could be more efficient to avoid surgery in this subset of patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2007

Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after lleo-caecal resection.

BACKGROUND: Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD. METHODS: Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization. RESULTS: Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79). CONCLUSION: Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection.

Adolescent↗
PubMed2006

No association between C-reactive protein gene polymorphisms and decrease of C-reactive protein serum concentration after infliximab treatment in Crohn's disease.

We recently showed an association between the FCGR3A V/F polymorphism and the biological response [assessed on the basis of a C-reactive protein (CRP) concentration decrease] to infliximab in Crohn's disease. The CRP and FCGR3A genes are located on the same 1q23 locus. The present study aimed: (i) to exclude a linkage disequilibrium (LD) between the two genes and (ii) to study the association between CRP polymorphisms and the response to infliximab, particularly the decrease in CRP after treatment, in Crohn's disease patients. FCGR3A (V/F) polymorphism and three CRP polymorphisms (-717G/A, 1444C/T, CRP 4A/G) were determined in 206 healthy blood donors and 189 Crohn's disease patients who had received infliximab for either refractory luminal or fistulizing Crohn's disease. Clinical response was defined as complete, partial or absent according to the same definition as in controlled trials. The biological response was defined on the basis of CRP decrease. There was no LD between CRP and FCGR3A in healthy donors or Crohn's disease patients. CRP polymorphisms had no impact on CRP decrease after infliximab. The proportions of Crohn's disease having a positive clinical or biological response were not statistically different among the various genotypes of CRP polymorphisms. There was no LD between CRP and FCGR3A polymorphisms. CRP polymorphisms were not associated with the response to infliximab in Crohn's disease.

Adolescent↗
PubMed2006

Lymphotoxin alpha gene in Crohn's disease patients: absence of implication in the response to infliximab in a large cohort study.

A haplotype in the lymphotoxin alpha (LTA) gene has been associated with a lack of response to infliximab in a small cohort of Crohn's disease (CD) patients. The present study aimed to confirm the implication of this haplotype in the response to infliximab in a larger cohort of Caucasian patients. The response to the first infusion with infliximab was evaluated in 214 Caucasian patients with either luminal (n=150) or fistulising (n=64) CD. Clinical response was based on the decrease in CD Activity Index (luminal) or on the evolution in the fistula discharge (fistulising). Biological response was assessed in 139 patients who had elevated C-reactive protein (CRP) before treatment and for whom CRP values were also available after treatment. A positive biological response was defined as a decrease in CRP of at least 25%. The patients were genotyped for six polymorphisms in the LTA gene. A positive clinical response was present in 65.4% of the patients and a positive biological response was observed in 80.6% of the patients. No association was found with any of the studied polymorphisms, nor with the previously published LTA haplotype and the response to infliximab. We could not confirm an association between the LTA locus and clinical or biological response to infliximab in a large cohort of CD patients.

Adult↗
PubMed2006

The TNF/ADAM 17 system: implication of an ADAM 17 haplotype in the clinical response to infliximab in Crohn's disease.

Infliximab, a chimeric anti-tumour necrosis factor (TNF)-alpha antibody induces a clinical response in 70% of Crohn's disease patients and the response to infliximab therapy could be partially determined by genetic factors. The implication of both transmembrane and soluble forms of the TNF-alpha in the mechanism of action of infliximab has been demonstrated. The aim of our work was first to perform a complete study of TNF variants role in the response to infliximab in Crohn's disease. Secondly, considering the role of ADAM 17 in TNF-alpha shedding, the ADAM 17 locus was also studied. The response to infliximab was evaluated in 222 Caucasian Crohn's disease patients with a luminal (n=160) or fistulizing (n=62) form of the disease. Clinical and biological response evaluation was based on the Crohn's Disease Activity Index score and C-reactive protein level evolutions, respectively. The entire TNF gene was sequenced on the complete cohort. Twelve single nucleotide polymorphisms spanning the ADAM 17 locus were studied and haplotypes rebuilt. A clinical response was observed in 64% of the patients and biological response in 77.1% of patients. No association was found between the TNF gene and the response to infliximab. One haplotype in the ADAM 17 region was associated with a clinical response to infliximab in CD patients (adjusted P=0.045). In conclusion, our results exclude, with a reasonable power, an implication of the TNF gene in the response to infliximab in Crohn's disease, but reveal a potential role of the ADAM 17 gene in this response.

ADAM Proteins↗
PubMed2003

Optimizing treatment with thioguanine derivatives in inflammatory bowel disease.

Thioguanine derivatives, azathioprine and 6-mercaptopurine, represent major drugs in the treatment of chronic active inflammatory bowel disease. They are effective in two-thirds of the patients and safe over the long term in patients who can tolerate them (80-90%). Recent progress in understanding the metabolism of these drugs and its implication in clinical practice have brought up new tools and strategies that are proposed to optimize treatment. In particular, the measurement and characterization of key enzymes and metabolites may have clinical impact. Thus, thiopurine methyl transferase genotyping and activity measurement, as well as erythrocytes, 6-thioguanine nucleotides and 6-methyl mercaptopurine levels, may help in some situations of intolerance or inefficacy with these drugs. Indications for starting and stopping treatment with thioguanine derivatives are also discussed.

Azathioprine↗
PubMed2002

Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up.

BACKGROUND & AIMS: Collagenous colitis (CC) is a well-described entity causing chronic diarrhea and characteristic histologic findings. Several treatment options have been suggested, but no controlled data are available. We conducted a placebo-controlled trial to show the clinical and histologic effects of budesonide in CC. METHODS: Twenty-eight patients were randomly assigned to receive placebo (n = 14) or budesonide 9 mg daily (n = 14) for 8 weeks. Patients were evaluated clinically, and blinded biopsy specimens were analyzed from fixed locations at weeks 0 and 8. Clinical response was defined as a decrease of at least 50% in the disease activity score (number of bowel movements in the last 7 days). At week 8, nonresponders received open-label budesonide for the next 8-week period; responders discontinued treatment and were followed up. RESULTS: Three patients discontinued the study prematurely. Intention-to-treat analysis showed clinical response in 8 of 14 patients in the budesonide group compared with 3 of 14 responders for placebo (P = 0.05) after 8 weeks of blinded therapy, together with improved stool consistency. Histologically, there was no change in the mean thickness of the collagen band but a significant decrease of the lamina propria infiltrate in the budesonide group (P < 0.001). CONCLUSIONS: Budesonide is efficacious in inducing short-term clinical response in CC with significant reduction of the histologic infiltrate in the lamina propria.

Adult↗
PubMed2002

NOD2/CARD15 does not influence response to infliximab in Crohn's disease.

BACKGROUND & AIMS: NOD2/CARD15 was recently identified as the first gene underlying Crohn's disease (CD) susceptibility. Monoclonal antibodies to tumor necrosis factor (TNF)-alpha (infliximab) are a potent treatment for CD, with about 70% of patients responding. It is not clear which factors influence treatment outcome. We assessed whether variants in NOD2/CARD15 are predictive for differences in clinical response. METHODS: Two hundred forty-five CD patients (86 fistulizing, 159 luminal) receiving infliximab in an expanded access program were genotyped for the 3 main associated variants of NOD2/CARD15, without knowledge of the treatment response. Short-term clinical response was assessed at 4 weeks (refractory) or 10 weeks (fistulizing) after first infliximab infusion, and the mean duration of response was calculated. In a subgroup of patients, production of TNF in response to lipopolysaccharide (LPS) in mucosal biopsy tissue was also determined by means of immunoassay, and results were related to the different NOD2/CARD15 genotypes. RESULTS: In total, 32.6% of patients carried mutations in NOD2/CARD15 (18.8% R702W, 8.6% G908R, and 10.2% 1007fs) compared with 15% in controls (P < 0.001). Despite observed differences in TNF production in mucosal biopsy tissue, there was no relationship between the overall presence of a mutation in NOD2/CARD15 or of any of the mutations separately and short-term infliximab response or response duration. Furthermore, multivariate analysis could not identify clinical characteristics that, in combination with NOD2/CARD15 mutations, were associated with response to infliximab. CONCLUSIONS: In this cohort of CD patients, the frequency of NOD2/CARD15 mutations was significantly greater than that of healthy controls. However, NOD2/CARD15 was not predictive of treatment outcome with infliximab in CD.

Adult↗
PubMed2002

Heartburn in Belgium: prevalence, impact on daily life, and utilization of medical resources.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a frequently occurring disease that may be considered a public health issue, particularly in developed countries. The specificity of heartburn for the diagnosis of GORD is good. Our aim was to define the prevalence of heartburn in Belgium, characterizing both its impact on everyday life and the ensuing use of medical resources. METHODS: Two thousand people living in Belgium, selected randomly after stratification, were interviewed face to face. The main question in the questionnaire used in this interview concerned the presence over the previous 12 months of a burning sensation in the epigastric and/or retrosternal region. This was followed by 21 secondary questions on the characteristics of the population studied, the impact of heartburn on everyday life, and the medical resources used. RESULTS: Twenty-eight per cent of the population interviewed reported heartburn. This symptom was present at least once a week in 42% of sufferers. Heartburn was more frequent in women than men (P < 0.05) and was not distributed uniformly throughout the various regions of the country (P < 0.05). Seventy-seven per cent of the people with heartburn found that it had a significantly negative impact on their daily lives (in 27%, this effect was strong). Heartburn associated with a substantial negative impact on daily life was characterized by a higher frequency of symptoms (P < 0.0001), a longer duration of the problem (P = 0.006), and the presence of pain (P < 0.0001) and anxiety (P < 0.0001). Fifty-six per cent of individuals with heartburn had already sought medical advice, 45% had undergone an upper-gastrointestinal tract endoscopy, and 59% were taking medications. Among patients complaining that heartburn had a substantial negative effect on their everyday lives, 21.6% had not sought medical advice and 22.2% did not take any medication. CONCLUSION: Heartburn is very frequent in Belgium and is associated with a considerable negative impact on everyday life. It also generates a significant use of medical resources. However, among the patients complaining of a substantial negative effect on their daily lives, one-fifth (which would represent 1.5% of the Belgian population) seemed to lack appropriate care.

Adolescent↗
PubMed2002

Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn's disease.

OBJECTIVE: Infliximab is an effective treatment for refractory or fistulizing Crohn's disease (CD). However, about 30% of patients do not respond to infliximab for unknown reasons. Identifying predictive factors of response is important for optimizing clinical management and for better understanding infliximab's mechanisms of action. The aim of this study was to assess whether demographic or clinical parameters influence short-term response to infliximab. METHODS: The first 240 CD patients of the Belgian Infliximab Expanded Access Program were studied for response to infliximab treatment and assessed at 4 (refractory luminal CD) or 10 wk (fistulizing CD) after the first infusion. Detailed demographic and clinical information on age, sex, type of disease (fistulizing or refractory), Crohn's Disease Activity Index score, C-reactive protein (CRP), smoking habits, disease duration, localization of disease, concomitant medication, and previous surgery were obtained from all patients. Logistic regression and decision tree analysis were performed. RESULTS: There were 73.5% responders and 26.5% nonresponders to treatment. Stepwise logistic regression identified age (OR = 0.971, 95% CI = 0.947-0.995, p = 0.018), isolated ileitis (OR = 0.359, 95% CI = 0.177-0.728, p = 0.004), and previous surgery (OR = 0.429, 95% CI = 0.233-0.787, p = 0.006) as inversely correlated with response, whereas isolated colitis (OR = 1.905, 95% CI = 1.010-3.597, p = 0.046) and concomitant immunosuppressive treatment (OR = 2.670, 95% CI = 1.430-5.016, p = 0.0022) were positively correlated with response to infliximab. Surprisingly, smoking habits were not retained as predictors for response. Decision tree analysis provided a working algorithm based on age and immunosuppressive treatment that warrants further exploration. CONCLUSIONS: In this large cohort of infliximab-treated CD patients, young age, Crohn's colitis, and concomitant immunosuppressive treatment were identified as independent variables favoring short-term response to infliximab.

Adult↗
PubMed2002

Epidemiology of inflammatory bowel diseases in the elderly in the province of Liège.

OBJECTIVE: Inflammatory bowel diseases (IBD) are heterogeneous diseases which affect preferentially young adults. The late onset could represent a particular form of expression of these diseases. The aim of our prospective study was to describe the incidence of IBD in patients older than 60 years as well as their clinical pattern in comparison with a population younger than 60. METHODS: A standardized questionnaire for each new case diagnosed in the province of Liège between 01/06/1993 and 31/05/1996 was completed. RESULTS: During the three years, 270 patients were enrolled. In group IBD > 60 years old, there were 60 new cases, including 23 cases with Crohn's disease (CD) (38%), 30 with ulcerative colitis (UC) (50%), and 7 with undetermined colitis (IC) (12%). The proportion of CD was significantly lower in the group IBD > 60 years old than in the group<60 (114 CD (54%), 81 UC (39%) and 15 IC (7%); P=0.04). The annual incidence tended to be higher for UC than for CD in group IBD > 60 (4.5 and 3.5 per 100,000, respectively) while it was the contrary in younger patients (3.4 and 4.8 per 100,000, respectively). There was no striking difference in the clinical features for both diseases in the two groups, except more frequent diarrhea, weight loss and extraintestinal symptoms in CD patients<60 years old. CONCLUSIONS: In the province of Liège, the incidence of IBD in people older than 60 years is high. IBD in the elderly is characterized by a lower proportion of CD than in the younger population. Clinical features tend to be the same whatever the age at diagnosis for each disease.

Age Factors↗
PubMedDate not supplied

The role of aminosalicylates in the treatment of ulcerative colitis.

Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two thirds of the patients, topical therapy also plays an important role. In mild/moderate active disease 5-ASA 4 g/d is as effective as oral corticosteroids. Ulcerative proctitis is treated with 2 x 500 mg or 1 x 1 g suppositories and proctosigmoiditis with 1 to 4 g enemas. Oral 5-ASA is also safe in maintenance treatment and is generally well tolerated. The risk of colorectal tumours is increased in patients with longstanding ulcerative colitis and epidemiological evidence indicates that chronic 5-ASA treatment reduces this risk. However, at present there is insufficient evidence to maintain patients on life-long 5-ASA maintenance treatment for this indication.

Administration, Oral↗