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de Vos, W. M.

Publications and source records attributed to de Vos, W. M..

6 recordsLinked to original sources

Infant gut microbiota in multi-child families converges with adults without a sibling-specific signature

The human gut microbiota undergoes rapid development during early life. Sibling presence has been associated with altered infant microbiota composition and accelerated maturation, but distinguishing direct microbial transmission between siblings from confounding by maternal reproductive history (parity) remains challenging. We analysed >5,000 faecal samples from >800 mother-father-infant triads in the Finnish HELMi birth cohort to characterise microbiota patterns that could inform underlying mechanisms. While sibling presence was associated with accelerated microbiota maturation and modest compositional differences, infants who both had siblings (or both lacked siblings) were no more similar to each other than mixed pairs. Instead, infants with siblings exhibited non-specific convergence with adult microbiota profiles and contributed fewer unique genera to their family metacommunities (infant-mother-father triads). Multi-child families harboured smaller but compositionally distinct metacommunities. These patterns challenge simple models of direct sibling transmission and suggest that multiple factors associated with family structure may jointly influence infant microbiota development, though specific mechanisms remain unclear.

microbiology↗

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice.

Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD), an acute pediatric vasculitis, remains unclear. We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria, or with short-chain fatty acids (SCFAs) produced by them, attenuated cardiovascular inflammation. Treatment with Amuc_1100, the TLR-2 signaling outer membrane protein from A. muciniphila, also decreased the severity of vascular inflammation. This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins acting on gut barrier function. IN BRIEFIt remains unclear whether changes in the intestinal microbiota composition are involved in the development of cardiovascular lesions associated with Kawasaki disease (KD), an immune-mediated vasculitis. Jena et al. observe alterations in the intestinal microbiota composition of mice developing vasculitis, characterized by reduced A. muciniphila and F. prausnitzii. Oral supplementation with either of these bacteria, live or pasteurized, or with bacteria-produced short-chain fatty acids (SCFAs) or Amuc_1100, the TLR-2 signaling outer membrane protein of A. muciniphila, was sufficient to alleviate the development of cardiovascular lesions in mice by promoting intestinal barrier function. HIGHLIGHTSO_LIAbsence or depletion of the microbiota decreases the severity of vasculitis in a murine model mimicking KD vasculitis. C_LIO_LISupplementation of B. wadsworthia and B. fragilis promotes murine KD vasculitis. C_LIO_LIDecreased abundances of F. prausnitzii and A. muciniphila are associated with the development of cardiovascular lesions in mice. C_LIO_LISupplementation with either live or pasteurized A. muciniphila and F. prausnitzii, or the TLR-2 signaling Amuc_1100, reduces the severity of vasculitis by promoting gut barrier function. C_LI

immunology↗

Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus

Biogeographic variations in the gut microbiota reflect host and environmental factors delineating human populations, and are pivotal to understand global patterns of host-microbiota interactions in health and prevalent lifestyle-related diseases, such as type 2 diabetes mellitus (T2D). Pakistani adults, having an exceptionally high prevalence of T2D, are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by 16S ribosomal RNA gene amplicon sequencing and qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis. Overall, urbanized Pakistanis gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.

microbiology↗

Drivers and Determinants of Strain Dynamics Following Faecal Microbiota Transplantation

Faecal microbiota transplantation (FMT) is an efficacious therapeutic intervention, but its clinical mode of action and underlying microbiome dynamics remain poorly understood. Here, we analysed the metagenomes associated with 142 FMTs, in a time series-based meta-study across five disease indications. We quantified strain-level dynamics of 1,089 microbial species based on their pangenome, complemented with 47,548 newly constructed metagenome-assembled genomes. Using subsets of procedural-, host- and microbiome-based variables, LASSO-regularised regression models accurately predicted the colonisation and resilience of donor and recipient microbes, as well as turnover of individual species. Linking this to putative ecological mechanisms, we found these sets of variables to be informative of the underlying processes that shape the post-FMT gut microbiome. Recipient factors and complementarity of donor and recipient microbiomes, encompassing entire communities to individual strains, were the main determinants of individual strain population dynamics, and mostly independent of clinical outcomes. Recipient community state and the degree of residual strain depletion provided a neutral baseline for donor strain colonisation success, in addition to inhibitive priority effects between species and conspecific strains, as well as putatively adaptive processes. Our results suggest promising tunable parameters to enhance donor flora colonisation or recipient flora displacement in clinical practice, towards the development of more targeted and personalised therapies.

microbiology↗

Intestinal transkingdom analysis on the impact of antibiotic perturbation in health and critical illness

Bacterial microbiota play a critical role in mediating local and systemic immunity, and shifts in these microbial communities have been linked to impaired outcomes in critical illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, and protozoa, are closely interlinked with the bacterial microbiota and their host, yet their collective role during antibiotic perturbation and critical illness remains to be elucidated. Here, multi-omics factor analysis (MOFA), a novel computational strategy to systematically integrate viral, fungal and bacterial sequence data, we describe the functional impact of exposure to broad-spectrum antibiotics in healthy volunteers and critically ill patients. We observe that a loss of the anaerobic intestinal environment is directly correlated with an overgrowth of aerobic pathobionts and their corresponding bacteriophages, as well as an absolute enrichment of opportunistic yeasts capable of causing invasive disease. These findings further illustrate the complexity of transkingdom interactions within the intestinal environment, and show that modulation of the bacterial component of the microbiome has implications extending beyond this kingdom alone.

microbiology↗

A comparative and functional genomics analysis of the genus Romboutsia provides insight into adaptation to an intestinal lifestyle

Cultivation-independent surveys have shown that the recently described genus Romboutsia within the family Peptostreptococcaceae is more diverse than previously acknowledged. The majority of Romboutsia-associated 16S rRNA gene sequences have an intestinal origin, but the specific roles that Romboutsia species play in the digestive tract are largely unknown. The complete genomes of the human intestinal isolate Romboutsia hominis FRIFIT (DSM 28814) and the soil isolate Romboutsia lituseburensis A25KT (DSM 797) were sequenced. An evaluation of the common traits of this recently defined genus was done based on comparative genome analysis of the two strains together with the previously elucidated genome of the type species Romboutsia ilealis CRIBT. These analyses showed that the genus Romboutsia covers a broad range of metabolic capabilities with respect to carbohydrate utilization, fermentation of single amino acids, anaerobic respiration and metabolic end products. Main differences between strains were found in their abilities to utilize specific carbohydrates, to synthesize vitamins and other cofactors, and their nitrogen assimilation capabilities. In addition, differences were found with respect to bile metabolism and motility-related gene clusters.

microbiology↗