Gut bacteria–host metabolic interplay during conventionalisation of the mouse germfree colon

Aidy, Sahar El; Derrien, Muriel; Merrifield, Claire A; Levenez, Florence; Doré, Joël; Boekschoten, Mark V.; Dekker, Jan; Holmes, Elaine; Zoetendal, Erwin G.; Baarlen, Peter van; Claus, Sandrine P.; Kleerebezem, Michiel

doi:10.1038/ismej.2012.142

Cited by 90 publications

(87 citation statements)

References 57 publications

(63 reference statements)

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“…In addition, previous studies using Gn and conventionalized mice revealed major molecular responses in metabolism, intestinal morphology and cell proliferation, and immunity as early as days 1-4 postconventionalization, with pronounced changes occurring after day 4 post-conventionalization. 57,58 Consistent with these findings, in our study more robust responses were observed on PBCD7, particularly in duodenum, illustrating the tissue-specific changes in the biological processes. However, detailed temporal analysis of transcriptome responses to lactobacilli colonization in neonatal Gn and conventional pigs (mimicking the infants) would provide better understanding of the biological processes modulated by these known probiotics.…”

Section: Discussionsupporting

confidence: 90%

In vivo gut transcriptome responses toLactobacillus rhamnosusGG andLactobacillus acidophilusin neonatal gnotobiotic piglets

et al. 2014

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Probiotics facilitate mucosal repair and maintain gut homeostasis. They are often used in adjunct with rehydration or antibiotic therapy in enteric infections. Lactobacillus spp have been tested in infants for the prevention or treatment of various enteric conditions. however, to aid in rational strain selection for specific treatments, comprehensive studies are required to delineate and compare the specific molecules and pathways involved in a less complex but biologically relevant model (gnotobiotic pigs). here we elucidated Lactobacillus rhamnosus (LGG) and L. acidophilus (LA) specific effects on gut transcriptome responses in a neonatal gnotobiotic (Gn) pig model to simulate responses in newly colonized infants. Whole genome microarray, followed by biological pathway reconstruction, was used to investigate the host-microbe interactions in duodenum and ileum at early (day 1) and later stages (day 7) of colonization. Both LA and LGG modulated common responses related to host metabolism, gut integrity, and immunity, as well as responses unique to each strain in Gn pigs. Our data indicated that probiotic establishment and beneficial effects in the host are guided by: (1) down-regulation or upregulation of immune function-related genes in the early and later stages of colonization, respectively, and (2) alternations in metabolism of small molecules (vitamins and/or minerals) and macromolecules (carbohydrates, proteins, and lipids). Pathways related to immune modulation and carbohydrate metabolism were more affected by LGG, whereas energy and lipid metabolism-related transcriptome responses were prominently modulated by LA. These findings imply that identification of probiotic strain-specific gut responses could facilitate the rational design of probiotic-based interventions to moderate specific enteric conditions.

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Section: Discussionsupporting

confidence: 90%

In vivo gut transcriptome responses toLactobacillus rhamnosusGG andLactobacillus acidophilusin neonatal gnotobiotic piglets

et al. 2014

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“…2, Table S2). Supporting this hypothesis, consistently higher tryptophan levels in urine were reported during the establishment of a gut microbiota compared with germfree animals 36 though another study reported lower serum tryptophan levels in conventional mice compared to germfree mice. 37 Interestingly, ex-germfree mice also displayed higher levels of phenylalanine, tyrosine, and tryptophan in the cerebral metabolome compared with germfree mice.…”

Section: Discussionmentioning

confidence: 88%

Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework

2015

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Keywords: human gut microbiome, in silico, metabolome, metabolic modelingThe gut microbiota is well known to affect host metabolic phenotypes. The systemic effects of the gut microbiota on host metabolism are generally evaluated via the comparison of germfree and conventional mice, which is impossible to perform for humans. Hence, it remains difficult to determine the impact of the gut microbiota on human metabolic phenotypes. We demonstrate that a constraint-based modeling framework that simulates "germfree" and "exgermfree" human individuals can partially fill this gap and allow for in silico predictions of systemic human-microbial cometabolism. To this end, we constructed the first constraint-based host-microbial community model, comprising the most comprehensive model of human metabolism and 11 manually curated, validated metabolic models of commensals, probiotics, pathogens, and opportunistic pathogens. We used this host-microbiota model to predict potential metabolic host-microbe interactions under 4 in silico dietary regimes. Our model predicts that gut microbes secrete numerous health-relevant metabolites into the lumen, thereby modulating the molecular composition of the body fluid metabolome. Our key results include the following: 1. Replacing a commensal community with pathogens caused a loss of important host metabolic functions. 2. The gut microbiota can produce important precursors of host hormone synthesis and thus serves as an endocrine organ. 3. The synthesis of important neurotransmitters is elevated in the presence of the gut microbiota. 4. Gut microbes contribute essential precursors for glutathione, taurine, and leukotrienes. This computational modeling framework provides novel insight into complex metabolic host-microbiota interactions and can serve as a powerful tool with which to generate novel, non-obvious hypotheses regarding host-microbe co-metabolism.

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“…Proteobacteria was the most abundant phylum in breast tissue, unlike in the vagina, oral cavity, bladder, skin, and gastrointestinal tract, where members of this phylum make up only a small pro- portion of the overall bacterial community (5,8,(31)(32)(33)(34) (36). It has also been documented that wild-type mice fed a high-fat diet have a gut microbiota enriched in Firmicutes (37).…”

Section: Discussionmentioning

confidence: 99%

Microbiota of Human Breast Tissue

Urbaniak

Cummins

Brackstone³

et al. 2014

Appl Environ Microbiol

403

376

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f ; Preclinical Imaging, Perkin Elmer, Alameda, California, USA g In recent years, a greater appreciation for the microbes inhabiting human body sites has emerged. In the female mammary gland, milk has been shown to contain bacterial species, ostensibly reaching the ducts from the skin. We decided to investigate whether there is a microbiome within the mammary tissue. Using 16S rRNA sequencing and culture, we analyzed breast tissue from 81 women with and without cancer in Canada and Ireland. A diverse population of bacteria was detected within tissue collected from sites all around the breast in women aged 18 to 90, not all of whom had a history of lactation. The principal phylum was Proteobacteria. The most abundant taxa in the Canadian samples were Bacillus (11.4%), Acinetobacter (10.0%), Enterobacteriaceae (8.3%), Pseudomonas (6.5%), Staphylococcus (6.5%), Propionibacterium (5.8%), Comamonadaceae (5.7%), Gammaproteobacteria (5.0%), and Prevotella (5.0%). In the Irish samples the most abundant taxa were Enterobacteriaceae (30.8%), Staphylococcus (12.7%), Listeria welshimeri (12.1%), Propionibacterium (10.1%), and Pseudomonas (5.3%). None of the subjects had signs or symptoms of infection, but the presence of viable bacteria was confirmed in some samples by culture. The extent to which these organisms play a role in health or disease remains to be determined.T he human body is home to a large and diverse population of bacteria with properties that are both harmful and beneficial to health (1-6), and for this reason there has been a strong push in recent years to fully characterize the bacteria associated with different parts of the body under different health conditions. These studies have been made possible with the use of deep-sequencing technologies, and sites once thought of as sterile, such as the stomach, bladder, and lungs, have now been shown to harbor an indigenous microbiota (7-9). We hypothesized that microbes may also be present in breast tissue given the known presence of bacteria in human milk (10). This is not surprising considering that skin and oral bacteria have access to the mammary ducts through the nipple (11), with some recent studies suggesting their source to be from the mother's gastrointestinal tract (12). We rationalized that given the nutrient-rich fatty composition of the female breast, the widespread vasculature and lymphatics, and the diffuse location of the lobules and ducts leading from the nipple, bacteria would be widespread within the mammary glands, irrespective of lactation. Thus, the objective of the study was to determine, using culture and nonculture methods, whether breast tissue contains a microbiome. To ensure that the results obtained were not an artifact of a single demographic, tissue was collected from two distant countries, Canada and Ireland. MATERIALS AND METHODS Clinical samples and study design (Canadian samples). Ethical approval for this study was obtained from Western Research Ethics Board andLawson Health Research Institute, London, Ontario, Canada. Patie...

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Gut bacteria–host metabolic interplay during conventionalisation of the mouse germfree colon

Cited by 90 publications

References 57 publications

In vivo gut transcriptome responses toLactobacillus rhamnosusGG andLactobacillus acidophilusin neonatal gnotobiotic piglets

In vivo gut transcriptome responses toLactobacillus rhamnosusGG andLactobacillus acidophilusin neonatal gnotobiotic piglets

Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework

Microbiota of Human Breast Tissue

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