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8
result(s) for
"Rega Institute for Medical Research [Leuven] "
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The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice
by
Aarhus University Hospital
,
Göteborgs Universitet = University of Gothenburg (GU)
,
Pons, Nicolas
in
38/77
,
45/22
,
45/23
2023
Abstract Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral–bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our ‘omics’ and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis.
Journal Article
Starvation responses impact interaction dynamics of human gut bacteria Bacteroides thetaiotaomicron and Roseburia intestinalis
2023
Abstract Bacterial growth often alters the environment, which in turn can impact interspecies interactions among bacteria. Here, we used an in vitro batch system containing mucin beads to emulate the dynamic host environment and to study its impact on the interactions between two abundant and prevalent human gut bacteria, the primary fermenter Bacteroides thetaiotaomicron and the butyrate producer Roseburia intestinalis. By combining machine learning and flow cytometry, we found that the number of viable B. thetaiotaomicron cells decreases with glucose consumption due to acid production, while R. intestinalis survives post-glucose depletion by entering a slow growth mode. Both species attach to mucin beads, but only viable cell counts of B. thetaiotaomicron increase significantly. The number of viable co-culture cells varies significantly over time compared to those of monocultures. A combination of targeted metabolomics and RNA-seq showed that the slow growth mode of R. intestinalis represents a diauxic shift towards acetate and lactate consumption, whereas B. thetaiotaomicron survives glucose depletion and low pH by foraging on mucin sugars. In addition, most of the mucin monosaccharides we tested inhibited the growth of R. intestinalis but not B. thetaiotaomicron. We encoded these causal relationships in a kinetic model, which reproduced the observed dynamics. In summary, we explored how R. intestinalis and B. thetaiotaomicron respond to nutrient scarcity and how this affects their dynamics. We highlight the importance of understanding bacterial metabolic strategies to effectively modulate microbial dynamics in changing conditions.
Journal Article
Discovery of alternative stable states in a synthetic human gut microbial community
by
Liu, Bin
,
Gonze, Didier
,
Simoens, Kenneth
in
Intestinal microflora
,
Life history
,
Life Sciences
2024
Several human-associated microbial communities exist in multiple configurations and can change their composition in response to perturbations, remaining in an altered state even after the perturbation ends. Multistability has been previously proposed to explain this behavior for gut microbiota in particular, but has not been clearly demonstrated experimentally. Here, we first investigated the life history strategies of three common human gut bacteria to identify mechanisms driving alternative states. We then used this data to build and parameterize a kinetic model, which predicted that alternative states emerge due to phenotype switching between subpopulations of the same species. Perturbation experiments supported these predictions, and confirmed the existence of alternative states. Finally, simulations showed that phenotype switching can also explain alternative states in larger communities. Thus, a transient perturbation combined with metabolic flexibility is sufficient for alternative communities to emerge, implying that they are not necessarily explained by differences between individuals.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://github.com/danielriosgarza/hungerGamesModel/blob/main/README.md
Ecological niche modelling and coalescent simulations to explore the recent geographical range history of five widespread bumblebee species in Europe
by
Varela, Sara
,
Kastally, Chedly
,
Mardulyn, Patrick
in
Biological evolution
,
Bombus
,
Bumblebees
2017
Aim Studying the changes in species ranges during the last glaciation event is an important step towards the understanding of the observed patterns of intra-specific genetic variability. We focused on bumblebees, an interesting biological model to address these questions because cold-adapted species are likely to have experienced different geographical range histories during the last glacial period compared to more commonly studied, strictly temperate, species. We investigated and compared historical hypotheses regarding the geographical range of five common and co-distributed West Palaearctic bumblebee species. Location Europe, West Palaearctic. Methods For each species, we inferred present and past (Last Glacial Maximum) distributions from species occurrence records, and present and past climatic data, using the ecological niche modelling (ENM) approach implemented in MAXENT. Based on genetic data previously obtained from the sequencing of three gene fragments (mitochondrial locus COI and two nuclear loci EF-1a and PEPCK), we then compared global and local patterns of genetic variation using several summary statistics as well as a visual mapping of genetic variation. Finally, we used a spatially explicit model of DNA sequence coalescence to test and compare four evolutionary scenarios derived from ENM results and patterns of genetic diversity. Results Ecological niche modelling results based on climatic data clearly suggested a range continuum in Europe during the last glaciation. Yet, the related evolutionary scenario involving such continuum was less supported than alternative scenarios involving a more fragmented distribution. Indeed, for the three out of five species for which genetic data allowed discriminating among tested scenarios, the scenario that included a fragmented range during the last glaciation was identified as the most likely. Main conclusions Although ENM suggested that bumblebees would have maintained a range continuum across Europe during the last glaciation, coalescent simulations tended to refute the persistence of a large range continuum for these species during this period. This suggests that even for cold-adapted species, the cooling periods have significantly shrunk and fragmented their respective ranges.
Journal Article
Quantifying time-dependent predictors for the international spatial spread of Highly Pathogenic Avian Influenza H5NX - focus on trade and surveillance efforts
by
Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
,
Tizzani, Paolo
,
Vrancken, Bram
in
Animal health
,
Animal Migration
,
Animals
2025
The multiple waves of intercontinental transmission of the highly pathogenic avian influenza (HPAI) H5Nx Gs/GD lineage since its identification in 1996 are testament to its resistance to control and prevention efforts. Knowledge of the predictors of HPAI international spread can help identify strengths as well as areas for improvement in surveillance and controlling HPAI. We used 10 years of data with quarterly granularity from the World Organization for Animal Health (WOAH), United Nations (UN), International Union for Conservation of Nature (IUCN), and genetic databases for 2.3.2.1c and 2.3.4.4b H5Nx clades, to determine the impact on international viral spread of (1) six categories of poultry commodities of legal international trade, (2) wild birds’ migration, (3) five types of preventive measures, (4) resources allocated to veterinary services, and (5) geographic distance between countries. Two analytical approaches were used: a generalized linear mixed model (GLMM) for all targeted countries, based on epidemiological, trade, and bird migration data. Then, phylogeography-informed generalized linear models (GLMs) with time-dependent predictors were specified for analyzing the HPAI spread between countries with available genetic data. The main conclusions of this study are that results suggested (1) a role of poultry trade in disease spread; (2) a role of migratory birds in disease spread; (3) a strong role of proximity between countries in disease spread; (4) a protective effect for resources allocated to veterinary services; and (5) a protective effect for precautions at borders in exposed countries (protective against informal trade). Our findings show the importance of proper implementation of preventive measures, as advocated in WOAH standards. In addition, our results show the complementarity of epidemiological, trade, biological, and genetic data to trace back international H5NX spread.
Journal Article
Exploiting gut microbial traits and trade-offs in microbiome-based therapeutics
2024
The clinical translation of therapeutics on the basis of human gut microorganisms is hampered by our limited knowledge of how microbes survive and adapt to fluctuating conditions in the gut. The systematic exploration of gut microbiome survival strategies and trade-offs will thus enable the design of more efficient microbiome-based interventions.
Journal Article
Bidirectional Interactions between Arboviruses and the Bacterial and Viral Microbiota in Aedes aegypti and Culex quinquefasciatus
by
Failloux, Anna-Bella
,
Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors ; Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
,
Institut Pasteur de la Guadeloupe ; Pasteur Network (Réseau International des Instituts Pasteur)
2022
In this study, we first utilized the single mosquito microbiome analysis, demonstrating a complex three-way interaction among arboviruses, resident microbiota, and the host, which is distinct for different arbovirus–mosquito combinations. Some of the previously described “core virus” increased in the mosquitos receiving viral blood meal, like Guadeloupe mosquito virus and Guadeloupe Culex tymo-like virus, suggesting their potential roles in ZIKV and WNV infection.
Journal Article
Evolution and phylogeography of Culex pipiens densovirus
by
Lequime, Sebastian
,
Justy, Fabienne
,
Courcelle, Maxime
in
Life Sciences
,
Microbiology and Parasitology
,
Virology
2019
Viruses of the Parvoviridae family infect a wide range of animals including vertebrates and invertebrates. So far, our understanding of parvovirus diversity is biased towards medically or economically important viruses mainly infecting vertebrate hosts, while invertebrate infecting parvoviruses-namely densoviruses-have been largely neglected. Here, we investigated the prevalence and the evolution of the only mosquito-infecting ambidensovirus, Culex pipiens densovirus (CpDV), from laboratory mosquito lines and natural populations collected worldwide. CpDV diversity generally grouped in two clades, here named CpDV-1 and -2. The incongruence of the different gene trees for some samples suggested the possibility of recombination events between strains from different clades. We further investigated the role of selection on the evolution of CpDV genome and detected many individual sites under purifying selection both in non-structural and structural genes. However, some sites in structural genes were under diversifying selection, especially during the divergence of CpDV-1 and -2 clades. These substitutions between CpDV-1 and -2 clades were mostly located in the capsid protein encoding region and might cause changes in host specificity or pathogenicity of CpDV strains from the two clades. However, additional functional and experimental studies are necessary to fully understand the protein conformations and the resulting phenotype of these substitutions between clades of CpDV.
Journal Article