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Michael France

Publications and source records attributed to Michael France.

8 recordsLinked to original sources
PubMed2026

VISTA: a classifier for metagenomic subspecies and community state typing of the vaginal microbiome.

Metagenomic community state types (mgCSTs) capture within-species genetic and functional diversity and community structure of the vaginal microbiome, enabling precise links between microbiome composition, function, and health-related risk. VISTA, the Vaginal Inference of Subspecies and Typing Algorithm, is a two-step classifier that assigns mgCSTs to vaginal metagenomes, providing standardized, scalable classifications.

bioinformatics↗
PubMed2026

Chlamydia trachomatis incidence in relation to vaginal microbiota dynamics, immunogenetics and exposures in a cohort of young student women in France.

BACKGROUND: Given the potential role of the vaginal microbiota in the acquisition of Chlamydia trachomatis infections, we aim to investigate its contribution together with immunogenetics and epidemiological exposures to the incidence of C. trachomatis in young women. METHODS: This study involved 313 female students aged 18-24 years from the i-Predict prevention trial in France. Participants provided four self-collected vaginal samples and filled four self-administered questionnaires every 6 months for 18 months. C. trachomatis-positive participants and negative controls with complete follow-up were selected for this analysis and submitted to chlamydia testing and to vaginal microbiota characterization using 16S rRNA amplicon sequencing. Thirteen human single nucleotide polymorphisms (SNPs) related to C. trachomatis susceptibility and severity were also assessed. RESULTS: Compared to 260 non-infected participants, Gardnerella spp., Fannyhessea vaginae and Prevotella timonensis were more abundant in C. trachomatis-incident participants (n=24) before infection. Having a CST IV at the preceding sample compared to a CST I (3.56 [1.08-11.70], p=0.037) was associated with increased risk of C. trachomatis acquisition, as well as having had multiple concomitant partners in the last 6 months (4.33 [1.19-15.72], p=0.028). Lifetime condom use was associated with decreased incidence (OR 0.38 [0.16-0.94], p=0.037). None of the tested human SNPs was associated with C. trachomatis infection. CONCLUSIONS: In this low-risk for C. trachomatis population, having a CST IV-AB vaginal microbiota and associated bacterial anaerobes was a risk factor for C. trachomatis acquisition after adjustment for other exposures. Condom use remains one of the main tools to prevent incidence.

C. trachomatis↗
PubMed2025

Immunosuppressants Rewire the Gut Microbiome-Alloimmune Axis Through Time-Dependent and Tissue-Specific Mechanisms.

BACKGROUND: Lifelong immunosuppressive therapy is required to prevent allograft rejection in organ transplantation. Current immunosuppressants effectively suppress adaptive and innate immune responses, but their broad, antigen-non-specific effects often result in severe off-target complications. It remains a significant unmet medical need in transplant medicine. RESULTS: In this study we investigated immunosuppressant effects of four major immunosuppressant classes, including tacrolimus, prednisone, mycophenolate mofetil (MMF), and fingolimod (FTY), on the gut microbiome, metabolic pathways, lymphoid architecture and lymphocyte trafficking after up to 30-day chronic exposure. Despite their distinct mechanisms of action and not designed to target the gut, all immunosuppressive drugs induced profound and time-dependent alterations in both intestine gene expression and gut microbiome composition. Progressive alterations from moderate early, drug-specific changes to a strikingly convergent microbial dysbiosis, marked by significant expansion of pathobionts of Muribaculaceae, occurred across all drug classes. Concurrently, all drugs uniformly induced significant suppression of mucosal immunity including B cell, immunoglobulin, and antigen recognition. Time-dependent changes in lymph node (LN) reorganization and cellular composition were also observed, marked by a progressive shift toward pro-inflammatory phenotypes in gut-draining mesenteric LNs and a gradual loss of tolerogenic architecture in peripheral LNs. Drug-specific metabolic alterations and distinct phases of intestinal transcriptional responses were also characterized. Notably, MMF and FTY demonstrated the most robust immunomodulatory properties, and were able to suppress alloantigen-induced inflammation through mediating regulatory T cell distribution and LN remodeling. CONCLUSIONS: Together, these findings highlight the underappreciated complexity and temporal dynamics immunosuppressants effects, particularly their impact on the gut and compartmentalized regulation of alloimmune in lymphoid tissues. Understanding these relationships offers new opportunities for refining immunosuppressive strategies to reduce treatment-related off-target complications and improve long-term organ transplant outcomes.

gut dysbiosis↗
PubMed2025

kSanity: A k-mer based application for precision bacterial strain detection and quantification.

MOTIVATION: Accurate detection and quantification of bacterial strains in clinical samples is necessary to measure their colonization and persistence. Past methods to achieve this relied either on strain-specific qPCR assays, or shotgun metagenomic read mapping approaches. The resident microbial community is a major source of interference in both assays because it can contain conspecific strains bearing similarity to the focal strain(s). RESULTS: We present kSanity, a k-mer based application for the detection and quantification of targeted bacterial strains in shotgun metagenomic data. Because kSanity uses exact string matches between the reads and reference, it is less sensitive to interference by conspecific strains. We test the performance of kSanity using a combination of in silico spike-in experiments, and in vivo observational data. Our results demonstrate that kSanity provides precise and accurate quantification of targeted bacterial strains, even when they are present at low sequence coverage in the metagenome. AVAILABILITY AND IMPLEMENTATION: kSanity is available at: https://github.com/ravel-lab/kSanity.

bacterial strain detection↗
PubMed2023

Strain-specific alterations in gut microbiome and host immune responses elicited by tolerogenic Bifidobacterium pseudolongum.

The beneficial effects attributed to Bifidobacterium are largely attributed to their immunomodulatory capabilities, which are likely to be species- and even strain-specific. However, their strain-specificity in direct and indirect immune modulation remain largely uncharacterized. We have shown that B. pseudolongum UMB-MBP-01, a murine isolate strain, is capable of suppressing inflammation and reducing fibrosis in vivo. To ascertain the mechanism driving this activity and to determine if it is specific to UMB-MBP-01, we compared it to a porcine tropic strain B. pseudolongum ATCC25526 using a combination of cell culture and in vivo experimentation and comparative genomics approaches. Despite many shared features, we demonstrate that these two strains possess distinct genetic repertoires in carbohydrate assimilation, differential activation signatures and cytokine responses signatures in innate immune cells, and differential effects on lymph node morphology with unique local and systemic leukocyte distribution. Importantly, the administration of each B. pseudolongum strain resulted in major divergence in the structure, composition, and function of gut microbiota. This was accompanied by markedly different changes in intestinal transcriptional activities, suggesting strain-specific modulation of the endogenous gut microbiota as a key to immune modulatory host responses. Our study demonstrated a single probiotic strain can influence local, regional, and systemic immunity through both innate and adaptive pathways in a strain-specific manner. It highlights the importance to investigate both the endogenous gut microbiome and the intestinal responses in response to probiotic supplementation, which underpins the mechanisms through which the probiotic strains drive the strain-specific effect to impact health outcomes.

Mice↗
PubMed2006

Use of ethylenediaminetetraacetic acid for in vivo stripping of columnar mucosa: pilot study in an experimental model.

BACKGROUND: Barrett's oesophagus is an important clinical problem that can lead to oesophageal adenocarcinoma. A variety of mucosal ablation strategies are now being applied in an attempt to prevent this, although they all can cause complications. Animal experiments that suggest that ethylenediaminetetraacetic acid (EDTA) could be a novel agent for ablation of Barrett's oesophagus are reported in this article. METHODS: Dark Agouti rats were used in all experiments. To determine the feasibility of using EDTA to strip intestinal type mucosa, segments of the small intestine were exposed in vitro to EDTA at various concentrations with or without agitation. The conditions required for EDTA to strip mucosa from a vascularized loop of small bowel were then optimized in vivo. Cannulated small bowel loops were irrigated with different concentrations of EDTA with or without pulsation of the irrigation solution. The effect of similar treatments on the normal mucosa of the rat oesophagus was then determined. Mucosal healing after EDTA stripping was studied in an isolated small bowel loop survival model. RESULTS: Ethylenediaminetetraacetic acid with agitation or pulsation resulted in stripping of the intestinal columnar mucosa in vitro and in vivo. The extent was influenced by the concentration of EDTA and duration of exposure. Squamous epithelium was relatively resistant to stripping. In the survival model the small bowel mucosa regenerated without stricture formation. CONCLUSION: Small bowel columnar mucosa can be removed by EDTA in vivo without stricture formation. A refinement of this approach could be applicable to the ablation of Barrett's oesophagus.

Animals↗
PubMed2002

Results of laparoscopic antireflux operations in patients who have Barrett's esophagus.

In most patients who have Barrett's esophagus and who are undergoing open or laparoscopic antireflux surgery, there is a significant improvement in symptom control that is equivalent to that in patients who have uncomplicated gastroesophageal reflux disease. The requirement for reoperation in patients with Barrett's esophagus may be slightly higher, although in the two laparoscopic series published to date, the rate is still only approximately 6%. How much this will increase with longer follow-up, time alone will tell, but given the good results in approximately 95% of patients operated to date, the authors do not believe that the diagnosis of Barrett's esophagus should be considered a blanket contraindication for laparoscopic antireflux surgery. Clearly, in most patients with Barrett's esophagus, an antireflux operation will not result in regression of Barrett's mucosa. It is still unclear whether antireflux surgery provides any protection against subsequent development of esophageal adenocarcinoma. What is clear, however, is that after antireflux surgery, patients who have Barrett's esophagus are still at risk for developing adenocarcinoma and should remain in surveillance programs. The authors believe that laparoscopic antireflux surgery is a safe and effective approach for the cure of reflux-related symptoms in patients who have Barrett's esophagus.

Barrett Esophagus↗