Biology subjects

Pons, N.

Publications and source records attributed to Pons, N..

4 recordsLinked to original sources

bioRxiv2018

Laparoscopic Roux-en-Y gastric bypass profoundly changes gut microbiota compared to laparoscopic sleeve gastrectomy: a metagenomic comparative analysis

BackgroundBariatric surgery is an effective therapeutic procedure for morbidly obese patients as it induces sustained weight loss. The two most common interventions are Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Roux-en-Y Gastric Bypass (LRYGB).\n\nObjectiveCharacterizing the gut microbiota changes induced by LSG and LRYGB.\n\nDesign89 and 108 patients who underwent LSG and LRYGB respectively, were recruited from three countries: USA, France and Switzerland. Stools were collected before and 6 months after surgery. Microbial DNA was analysed with shotgun metagenomic sequencing (SOLiD 5500xl Wildfire). MSPminer, a novel innovative tool to characterize new in silico biological entities, was used to identify 715 Metagenomic Species Pan-genome (MSPs). 148 functional modules were analysed using GOmixer and KEGG database.\n\nResultsBoth interventions resulted in a similar increase of Shannons diversity index and gene richness of gut microbiota, in parallel with weight loss, but the changes of microbial composition were different. LRYGB led to higher relative abundance of aero-tolerant bacteria, such as Escherichia coli and buccal species, such as Streptococcus and Veillonella spp. In contrast, anaerobes such as Clostridium were more abundant after LSG, suggesting better conservation of anaerobic conditions in the gut. Function-level changes included higher potential for bacterial use of supplements such as vitamin B12, B1 and iron upon LRYGB. Moreover, after LRYGB, potential for nitrate and Trimethylamine oxidized (TMAO) respiration was detected.\n\nConclusionMicrobiota changes after bariatric surgery depend on the nature of the intervention. LRYGB induces greater taxonomic and functional changes in gut microbiota than LSG and may lead to a more dysbiotic microbiome. Possible long-term health consequences of these alterations remain to be established.\n\nSignificance of this studyO_ST_ABSWhat is already known on this subject?C_ST_ABSPrevious studies have reported changes of microbial composition after bariatric surgery with shotgun metagenomics, but lacked statistical power to document the changes. Important shifts in gut microbiome have been observed after LRYGB and LSG with an increase of aerotolerants from buccal microbiota. However, it is not clear how different the changes are between LRYGB and LSG although both procedures induce quite similar results with respect to weight loss, comorbidities remission and global glycaemic improvement outcomes.\n\nWhat are the new findings?LSG and LRYGB have specific but different impacts on gut microbial composition 6 months after bariatric surgery. The changes could be related to specific physiological effects. LRYGB promotes an important invasion of oral colonizers with Veillonella and Streptococcus genera. In contrast, these changes were less important after LSG. Moreover, microbial transportation potential of iron and vitamin B12 were also higher after LRYGB than LSG. We concluded that the type of surgery leads to different gut microbiome and functional profiles.\n\nHow might it impact on clinical practice in the foreseeable future?Microbiome composition and functional profiles are not altered to the same extent by LRYGB and LSG 6 months after surgery. This difference should be considered when advising the patient on the type of bariatric surgery or post op diet.

microbiology↗

bioRxiv2017

CDC20B is required for deuterosome-mediated centriole production in multiciliated cells

Multiciliated cells (MCCs) harbour dozens to hundreds of motile cilia, which beat in a synchronized and directional manner, thus generating hydrodynamic forces important in animal physiology. In vertebrates, MCC differentiation critically depends on the synthesis and release of numerous centrioles by specialized structures called deuterosomes. Little is known about the composition, organization and regulation of deuterosomes. Here, single-cell RNA sequencing reveals that human deuterosome-stage MCCs are characterized by the expression of many cell cycle-related genes. We further investigated the uncharacterized vertebrate-specific cell division cycle 20B (CDC20B) gene, the host gene of microRNA-449abc. We show that the CDC20B protein associates to deuterosomes and is required for the release of centrioles and the subsequent production of cilia in mouse and Xenopus MCCs. CDC20B interacts with PLK1, which has been shown to coordinate centriole disengagement with the protease Separase in mitotic cells. Strikingly, over-expression of Separase rescued centriole disengagement and cilia production in CDC20B-deficient MCCs. This work reveals the shaping of a new biological function, deuterosome-mediated centriole production in vertebrate MCCs, by adaptation of canonical and recently evolved cell cycle-related molecules.

cell biology↗

bioRxiv2017

Prediction of the intestinal resistome by a novel 3D-based method

The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens. Yet, this question remains hypothetical because of the difficulty to identify ARDs from intestinal bacteria. Here, we developed and validated a new annotation method (called pairwise comparative modelling, PCM) based on homology modelling in order to characterize the Human resistome. We were able to predict 6,095 ARDs in a 3.9 million protein catalogue from the Human intestinal microbiota. We found that predicted ARDs (pdARDs) were distantly related to known ARDs (mean amino-acid identity 29.8%). Among 3,651 pdARDs that were identified in metagenomic species, 3,489 (95.6%) were assumed to be located on the bacterial chromosome. Furthermore, genes associated with mobility were found in the neighbourhood of only 7.9% (482/6,095) of pdARDs. According to the composition of their resistome, we were able to cluster subjects from the MetaHIT cohort (n=663) into 6 \"resistotypes\". Eventually, we found that the relative abundance of pdARDs was positively associated with gene richness, but not when subjects were exposed to antibiotics. Altogether, our results support that most ARDs in the intestinal microbiota should be considered as intrinsic genes of commensal microbiota with a low risk of transfer to bacterial pathogens.

microbiology↗

bioRxiv2017

Protection of the human gut microbiome from antibiotics

BackgroundAntibiotics are life-saving drugs but severely affect the gut microbiome with short term consequences including diarrhoea, Clostridium difficile infections and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.\n\nMethodsWe performed a randomized controlled trial (ClinicalTrials.gov NCT02176005) in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in two parallel groups, with or without DAV132 co-administration. Two control goups of 8 volunteers each receiving DAV132 alone, or a non-active substitute, were added.\n\nResultsThe co-administration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex-vivo.\n\nConclusionsDAV132 was highly effective to protect the gut microbiome of moxifloxacin - treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.

clinical trials↗