Browsing by Subject "HUMAN GUT MICROBIOME"

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  • Geerlings, Sharon Y.; Kostopoulos, Ioannis; de Vos, Willem M.; Belzer, Clara (2018)
    Akkermansia muciniphila is a mucin-degrading bacterium of the phylum Verrucomicrobia. Its abundance in the human intestinal tract is inversely correlated to several disease states. A. muciniphila resides in the mucus layer of the large intestine, where it is involved in maintaining intestinal integrity. We explore the presence of Akkermansia-like spp. based on its 16S rRNA sequence and metagenomic signatures in the human body so as to understand its colonization pattern in time and space. A. muciniphila signatures were detected in colonic samples as early as a few weeks after birth and likely could be maintained throughout life. The sites where Akkermansia-like sequences (including Verrucomicrobia phylum and/or Akkermansia spp. sequences found in the literature) were detected apart from the colon included human milk, the oral cavity, the pancreas, the biliary system, the small intestine, and the appendix. The function of Akkermansia-like spp. in these sites may differ from that in the mucosal layer of the colon. A. muciniphila present in the appendix or in human milk could play a role in the re-colonization of the colon or breast-fed infants, respectively. In conclusion, even though A. muciniphila is most abundantly present in the colon, the presence of Akkermansia-like spp. along the digestive tract indicates that this bacterium might have more functions than those currently known.
  • Kolmeder, Carolin A.; Salojarvi, Jarkko; Ritari, Jarmo; de Been, Mark; Raes, Jeroen; Falony, Gwen; Vieira-Silva, Sara; Kekkonen, Riina A.; Corthals, Garry L.; Palva, Airi; Salonen, Anne; de Vos, Willem M. (2016)
    Recent metagenomic studies have demonstrated that the overall functional potential of the intestinal microbiome is rather conserved between healthy individuals. Here we assessed the biological processes undertaken in-vivo by microbes and the host in the intestinal tract by conducting a metaproteome analysis from a total of 48 faecal samples of 16 healthy adults participating in a placebo-controlled probiotic intervention trial. Half of the subjects received placebo and the other half consumed Lactobacillus rhamnosus GG for three weeks (10(10) cfu per day). Faecal samples were collected just before and at the end of the consumption phase as well as after a three-week follow-up period, and were processed for microbial composition and metaproteome analysis. A common core of shared microbial protein functions could be identified in all subjects. Furthermore, we observed marked differences in expressed proteins between subjects that resulted in the definition of a stable and personalized microbiome both at the mass-spectrometry-based proteome level and the functional level based on the KEGG pathway analysis. No significant changes in the metaproteome were attributable to the probiotic intervention. A detailed taxonomic assignment of peptides and comparison to phylogenetic microarray data made it possible to evaluate the activity of the main phyla as well as key species, including Faecalibacterium prausnitzii. Several correlations were identified between human and bacterial proteins. Proteins of the human host accounted for approximately 14% of the identified metaproteome and displayed variations both between and within individuals. The individually different human intestinal proteomes point to personalized host-microbiota interactions. Our findings indicate that analysis of the intestinal metaproteome can complement gene-based analysis and contributes to a thorough understanding of the activities of the microbiome and the relevant pathways in health and disease.
  • Wacklin, Pirjo; Tuimala, Jarno; Nikkila, Janne; Tims, Sebastian; Makivuokko, Harri; Alakulppi, Noora; Laine, Pia; Rajilic-Stojanovic, Mirjana; Paulin, Lars; de Vos, Willem M.; Matto, Jaana (2014)
  • Ritari, Jarmo; Salojärvi, Jarkko; Lahti, Leo; de Vos, Willem M. (2015)
    Background: Current sequencing technology enables taxonomic profiling of microbial ecosystems at high resolution and depth by using the 16S rRNA gene as a phylogenetic marker. Taxonomic assignation of newly acquired data is based on sequence comparisons with comprehensive reference databases to find consensus taxonomy for representative sequences. Nevertheless, even with well-characterised ecosystems like the human intestinal microbiota it is challenging to assign genus and species level taxonomy to 16S rRNA amplicon reads. A part of the explanation may lie in the sheer size of the search space where competition from a multitude of highly similar sequences may not allow reliable assignation at low taxonomic levels. However, when studying a particular environment such as the human intestine, it can be argued that a reference database comprising only sequences that are native to the environment would be sufficient, effectively reducing the search space. Results: We constructed a 16S rRNA gene database based on high-quality sequences specific for human intestinal microbiota, resulting in curated data set consisting of 2473 unique prokaryotic species-like groups and their taxonomic lineages, and compared its performance against the Greengenes and Silva databases. The results showed that regardless of used assignment algorithm, our database improved taxonomic assignation of 16S rRNA sequencing data by enabling significantly higher species and genus level assignation rate while preserving taxonomic diversity and demanding less computational resources. Conclusion: The curated human intestinal 16S rRNA gene taxonomic database of about 2500 species-like groups described here provides a practical solution for significantly improved taxonomic assignment for phylogenetic studies of the human intestinal microbiota.
  • Shetty, Sudarshan A.; Hugenholtz, Floor; Lahti, Leo; Smidt, Hauke; de Vos, Willem M. (2017)
    High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss key concepts of the human intestinal microbiome landscape, i.e. the compositional and functional 'core', the presence of community types and the existence of alternative stable states. Genomic investigation of core taxa revealed functional redundancy, which is expected to stabilize the ecosystem, as well as taxa with specialized functions that have the potential to shape the microbiome landscape. The contrast between Prevotella-and Bacteroides-dominated systems has been well described. However, less known is the effect of not so abundant bacteria, for example, Dialister spp. that have been proposed to exhibit distinct bistable dynamics. Studies employing time-series analysis have highlighted the dynamical variation in the microbiome landscape with and without the effect of defined perturbations, such as the use of antibiotics or dietary changes. We incorporate ecosystem-level observations of the human intestinal microbiota and its keystone species to suggest avenues for designing microbiome modulation strategies to improve host health.
  • Faust, Karoline; Lahti, Leo; Gonze, Didier; de Vos, Willem M.; Raes, Jeroen (2015)
    The recent increase in the number of microbial time series studies offers new insights into the stability and dynamics of microbial communities, from the world's oceans to human microbiota. Dedicated time series analysis tools allow taking full advantage of these data. Such tools can reveal periodic patterns, help to build predictive models or, on the contrary, quantify irregularities that make community behavior unpredictable. Microbial communities can change abruptly in response to small perturbations, linked to changing conditions or the presence of multiple stable states. With sufficient samples or time points, such alternative states can be detected. In addition, temporal variation of microbial interactions can be captured with time-varying networks. Here, we apply these techniques on multiple longitudinal datasets to illustrate their potential for microbiome research.
  • Siljander, Heli; Honkanen, Jarno; Knip, Mikael (2019)
    The steep increase in the incidence of type 1 diabetes (T1D), in the Western world after World War II, cannot be explained solely by genetic factors but implies that this rise must be due to crucial interactions between predisposing genes and environmental changes. Three parallel phenomena in early childhood – the dynamic development of the immune system, maturation of the gut microbiome, and the appearance of the first T1D-associated autoantibodies – raise the question whether these phenomena might reflect causative relationships. Plenty of novel data on the role of the microbiome in the development of T1D has been published over recent years and this review summarizes recent findings regarding the associations between islet autoimmunity, T1D, and the intestinal microbiota.
  • Lehtimaki, Jenni; Karkman, Antti; Laatikainen, Tiina; Paalanen, Laura; von Hertzen, Leena; Haahtela, Tari; Hanski, Ilkka; Ruokolainen, Lasse (2017)
    The composition of human microbiota is affected by a multitude of factors. Understanding the dynamics of our microbial communities is important for promoting human health because microbiota has a crucial role in the development of inflammatory diseases, such as allergies. We have studied the skin microbiota of both arms in 275 Finnish children of few months old to teenagers living in contrasting environments. We show that while age is a major factor affecting skin microbial composition, the living environment also discriminates the skin microbiota of rural and urban children. The effect of environment is age-specific; it is most prominent in toddlers but weaker for newborns and non-existent for teenagers. Within-individual variation is also related to age and environment. Surprisingly, variation between arms is smaller in rural subjects in all age groups, except in teenagers. We also collected serum samples from children for characterization of allergic sensitization and found a weak, but significant association between allergic sensitization and microbial composition. We suggest that physiological and behavioral changes, related to age and the amount of contact with environmental microbiota, jointly influence the dynamics of the skin microbiota, and explain why the association between the living environment skin microbiota is lost in teenager.
  • Kolmeder, Carolin A.; de Vos, Willem M. (2021)
    It is known for more than 100 years that the intestinal microbes are important for the host's health and the last decade this is being intensely studied with a focus on the mechanistic aspects. Among the fundamental functions of the intestinal microbiome are the priming of the immune system, the production of essential vitamins and the energy harvest from foods. By now, several dozens of diseases, both intestinal and non-intestinal related, have been associated with the intestinal microbiome. Initially, this was based on the description of the composition between groups of different health status or treatment arms based on phylogenetic approaches based on the 16S rRNA gene sequences. This way of analysis has mostly moved to the analysis of all the genes or transcripts of the microbiome i.e. metagenomics and meta-transcriptomics. Differences are regularly found but these have to be taken with caution as we still do not know what the majority of genes of the intestinal microbiome are capable of doing. To circumvent this caveat researchers are studying the proteins and the metabolites of the microbiome and the host via metaproteomics and metabolomics approaches. However, also here the complexity is high and only a fraction of signals obtained with high throughput instruments can be identified and assigned to a known protein or molecule. Therefore, modern microbiome research needs advancement of existing and development of new analytical techniques. The usage of model systems like intestinal organoids where samples can be taken and processed rapidly as well as microfluidics systems may help. This review aims to elucidate what we know about the functionality of the human intestinal microbiome, what technologies are advancing this knowledge, and what innovations are still required to further evolve this actively developing field. (C) 2020 The Authors. Published by Elsevier B.V.
  • Depommier, Clara; Everard, Amandine; Druart, Celine; Maiter, Dominique; Thissen, Jean-Paul; Loumaye, Audrey; Hermans, Michel P.; Delzenne, Nathalie M.; de Vos, Willem M.; Cani, Patrice D. (2021)
    Reduction of A. muciniphila relative abundance in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, our study aimed at identifying metabolic signatures associated with beneficial properties of alive and pasteurized A. muciniphila when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Our data highlighted either shared or specific alterations in the metabolome according to the form of A. muciniphila administered with respect to a control group. Common responses encompassed modulation of amino acid metabolism, characterized by reduced levels of arginine and alanine, alongside several intermediates of tyrosine, phenylalanine, tryptophan, and glutathione metabolism. The global increase in levels of acylcarnitines together with specific modulation of acetoacetate also suggested induction of ketogenesis through enhanced beta-oxidation. Moreover, our data pinpointed some metabolites of interest considering their emergence as substantial compounds pertaining to health and diseases in the more recent literature.
  • Flandroy, Lucette; Poutahidis, Theofilos; Berg, Gabriele; Clarke, Gerard; Dao, Maria-Carlota; Decaestecker, Ellen; Furman, Eeva; Haahtela, Tari; Massart, Sebastien; Plovier, Hubert; Sanz, Yolanda; Rook, Graham (2018)
    Plants, animals and humans, are colonized by microorganisms (microbiota) and transiently exposed to countless others. The microbiota affects the development and function of essentially all organ systems, and contributes to adaptation and evolution, while protecting against pathogenic microorganisms and toxins. Genetics and lifestyle factors, including diet, antibiotics and other drugs, and exposure to the natural environment, affect the composition of the microbiota, which influences host health through modulation of interrelated physiological systems. These include immune system development and regulation, metabolic and endocrine pathways, brain function and epigenetic modification of the genome. Importantly, parental microbiotas have transgenerational impacts on the health of progeny. Humans, animals and plants share similar relationships with microbes. Research paradigms from humans and other mammals, amphibians, insects, planktonic crustaceans and plants demonstrate the influence of environmental microbial ecosystems on the microbiota and health of organisms, and indicate links between environmental and internal microbial diversity and good health. Therefore, overlapping compositions, and interconnected roles of microbes in human, animal and plant health should be considered within the broader context of terrestrial and aquatic microbial ecosystems that are challenged by the human lifestyle and by agricultural and industrial activities. Here, we propose research priorities and organizational, educational and administrative measures that will help to identify safe microbe-associated health-promoting modalities and practices. In the spirit of an expanding version of "One health" that includes environmental health and its relation to human cultures and habits (EcoHealth), we urge that the lifestyle-microbiota-human health nexus be taken into account in societal decision making. (C) 2018 The Authors. Published by Elsevier B.V.
  • Fernández, Leónides; Pannaraj, Pia S.; Rautava, Samuli; Rodríguez, Juan M. (2020)
    Human milk contains a dynamic and complex site-specific microbiome, which is not assembled in an aleatory way, formed by organized microbial consortia and networks. Presence of some genera, such as Staphylococcus, Streptococcus, Corynebacterium, Cutibacterium (formerly known as Propionibacterium), Lactobacillus, Lactococcus and Bifidobacterium, has been detected by both culture-dependent and culture-independent approaches. DNA from some gut-associated strict anaerobes has also been repeatedly found and some studies have revealed the presence of cells and/or nucleic acids from viruses, archaea, fungi and protozoa in human milk. Colostrum and milk microbes are transmitted to the infant and, therefore, they are among the first colonizers of the human gut. Still, the significance of human milk microbes in infant gut colonization remains an open question. Clinical studies trying to elucidate the question are confounded by the profound impact of non-microbial human milk components to intestinal microecology. Modifications in the microbiota of human milk may have biological consequences for infant colonization, metabolism, immune and neuroendocrine development, and for mammary health. However, the factors driving differences in the composition of the human milk microbiome remain poorly known. In addition to colostrum and milk, breast tissue in lactating and non-lactating women may also contain a microbiota, with implications in the pathogenesis of breast cancer and in some of the adverse outcomes associated with breast implants. This and other open issues, such as the origin of the human milk microbiome, and the current limitations and future prospects are addressed in this review.