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Moll, J. M.

Publications and source records attributed to Moll, J. M..

3 recordsLinked to original sources

Sex shapes the human genitourinary microbiome, including many species recognized as uropathogens: urine profiles from a population-level shotgun metagenomics study

Background: The urinary tract was long considered sterile. The discovery of the urinary microbiome has attracted interest in its role in urinary health and disease. Population-level urinary microbiome composition remains poorly defined and previous studies relied on selected populations and low-resolution sequencing. We characterized the microbial composition of voided urine from adults without urinary symptoms in a large Swedish population cohort to establish a population-based reference for microorganisms detected in voided urine using shotgun metagenomics. Methods: We performed shotgun metagenomic sequencing of voided urine samples from 2,062 participants of the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS; 55% women, 50-65 years). Results: Among 3,668 identified species, 90% were classified at the species level. Microbial profiles differed substantially between sexes, with lactobacilli and bifidobacteria enriched in females, while Cutibacterium acnes, Enterococcus and Propionimicrobium lymphophilum were enriched in males. Recognized uropathogens, including Enterococcus faecalis and Escherichia coli, were frequently detected despite participants having no urinary symptoms. Males showed higher alpha diversity (Shannon and inverse Simpson indices), whereas richness did not differ by sex. Age showed only modest associations with alpha diversity, and beta diversity differed by sex but showed minimal age-related variation. Conclusions: This study provides a population-based reference for interpreting microorganisms detected in routine voided urine samples. Biological sex was the principal determinant of microbial composition, supporting routine consideration of sex in future studies of the urogenital microbiota using routine voided urine samples.

microbiology↗

Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn's disease

Patients with Crohns disease (CD) exhibit great heterogeneity in disease presentation and treatment responses, where distinct gut microbiota-host interplays may play part in the yet unresolved disease etiology. We here characterized absolute and relative single and multi-coating of gut bacteria with immunoglobulin (Ig)A, IgG1, IgG2, IgG3 and IgG4 in CD patients and healthy controls. Patients with severe disease exhibited distinctly higher gut bacterial IgG2-coating. IgG2-coated bacteria included both known pathogenic and non-pathogenic bacteria that co-existed in communities with two non-coated gut pathobionts Campylobacter and Mannheimia. These latter two exhibited low prevalence, rarely coincided, and were strongly enriched during disease flares in CD patients across independent and geographically distant cohorts. Since antibody-coating of gut pathobionts diminishes epithelial invasion and inflammatory processes, escape from coating by specific gut pathobionts may be a mechanism related to disease flares in the subgroup of CD patients with severe disease.

immunology↗

Breastmilk-promoted bifidobacteria produce aromatic lactic acids in the infant gut

Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. We here demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactate, phenyllactate and 4-hydroxyphenyllactate) via a previously unrecognised aromatic lactate dehydrogenase. By longitudinal profiling of the gut microbiota composition and metabolome of stool samples of infants obtained from birth until 6 months of age, we show that stool concentrations of aromatic lactic acids are determined by the abundance of human milk oligosaccharide degrading Bifidobacterium species containing the aromatic lactate dehydrogenase. We demonstrate that stool concentrations of Bifidobacterium-derived indolelactate, the most abundant aromatic lactic acid in vivo, are associated with the capacity of infant stool samples to activate the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homeostasis and immune responses. Finally, we show that indolelactate modulates ex vivo immune responses of human CD4+ T-cells and monocytes in a dose-dependent manner by acting as an agonist of both, the AhR and hydroxycarboxylic acid receptor 3 (HCAR3). Our findings reveal that breastmilk-promoted Bifidobacterium produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.

microbiology↗