Dynamics of the Microbiota in Response to Host Infection

Longitudinal studies of the microbiota are important for discovering changes in microbial communities that affect the host. The complexity of these ecosystems requires rigorous integrated experimental and computational methods to identify temporal signatures that promote physiologic or pathophysiologic responses in vivo. Employing a murine model of infectious colitis with the pathogen Citrobacter rodentium, we generated a 2-month time-series of 16S rDNA gene profiles, and quantitatively cultured commensals, from multiple intestinal sites in infected and uninfected mice. We developed a computational framework to discover time-varying signatures for individual taxa, and to automatically group signatures to identify microbial sub-communities within the larger gut ecosystem that demonstrate common behaviors. Application of this model to the 16S rDNA dataset revealed dynamic alterations in the microbiota at multiple levels of resolution, from effects on systems-level metrics to changes across anatomic sites for individual taxa and species. These analyses revealed unique, time-dependent microbial signatures associated with host responses at different stages of colitis. Signatures included a Mucispirillum OTU associated with early disruption of the colonic surface mucus layer, prior to the onset of symptomatic colitis, and members of the Clostridiales and Lactobacillales that increased with successful resolution of inflammation, after clearance of the pathogen. Quantitative culture data validated findings for predominant species, further refining and strengthening model predictions. These findings provide new insights into the complex behaviors found within host ecosystems, and define several time-dependent microbial signatures that may be leveraged in studies of other infectious or inflammatory conditions

Autogenic versus environmental control during development of river biofilm

In the natural environment, microbial community structure of river biofilm is controlled by biotic and abiotic factors. This study explored the capacity to manipulate the structure of microbial communities by modifying environmental conditions during the course of biofilm development. River epilithic biofilm was cultivated in situ on artificial substrates placed parallel to river water flow. Substrates were incubated for 3 and 5.5 weeks in river to allow natural biofilm development, at two sites with contrasting physico-chemical characteristics. The first site (Aurade´ , Gers, France) was located in an agricultural watershed basin and the second site (Larroque, Haute-Garonne, France) was located in a forested watershed basin. After 3 weeks of biofilm development, a subset of substrates was collected from one site and transplanted to the second site where they remained for 2.5 further weeks. Epilithic bacterial community structure (at 3 weeks from each site and at 5.5 weeks from biofilms with and without transplantation) was assessed using PCR-DGGE of 16S rDNA fragment. Biofilm biomass was estimated using ash free dry mass (AFDM). After 3 weeks of development, biofilms from the two sites exhibited comparable AFDM values (average of 1.4¡0.2 g.mx2). A difference between the two sites was observed after 5.5 weeks of development: AFDM decreased for biofilms from the agricultural watershed basin (from 1.4 to 0.18 g.mx2) as a consequence of grazing pressure (Bithynia), and increased for biofilms from the forested agricultural watershed (from 1.4 to 2.6 g.mx2). Microbial community analyses revealed a differentiated community structure between biofilms from the different sites and exhibited a change of microbial community structure after 5.5 weeks of biofilm development. These observations confirm a process of ecological succession in microbial communities. Changing the incubation site during biofilm development modified the trajectory of these ecological successions, suggesting that site characteristics mainly conditioned the structure of these microbial communities

Impact of ocean acidification on the intestinal microbiota of the marine sea bream (Sparus aurata L.)

Within a scenario of increasing atmospheric CO2 and ocean acidification (OA), it is highly relevant to investigate its impacts not only on fish performance but also on fish intestinal microbiome and how that reflects on host performance and health. The main objective of this study was to establish if the intestinal microbiota of the sea bream (Sparus aurata) was affected by high level of CO2 in line with the predictions for this century. The bacterial communities of the intestinal fluid were characterized in animals kept at the present-day level of CO2 (400 μatm) and in animals switched to high CO2 (1200 μatm) for 1 month. Bacterial taxa identification was based on molecular methods, using the DNA coding for the 16S ribosomal RNA and primers targeting the regions V1-V3. Amplicons obtained from DNA samples of animals in the same tank were combined, cloned to obtain a bacterial DNA library, and the clones were sequenced. No significant differences were found between the two treatments for alpha diversity. However, beta diversity analysis revealed distinct dysbiosis in response to hypercapnia, with phylum Firmicutes absent from the bacterial communities of fish exposed to 1200 μatm CO2, whereas Proteobacteria relative abundance was increased at elevated CO2, due to the presence of Gammaproteobacteria (Vibrionaceae and Alteromonadaceae), a class not present in the control samples. This study provides a first glimpse at the impact of OA in fish intestinal microbiota and highlights potential downstream effects to the general condition of fishes under hypercapnia.Funding Agency Portuguese Foundation for Science and Technology PTDC/MAR-BIO/3034/2014 Portuguese Foundation for Science and Technology UID/Multi/04326/2019 Ministry of Science and Higher Education, Polandinfo:eu-repo/semantics/publishedVersio

The Bifidogenic Effect Revisited-Ecology and Health Perspectives of Bifidobacterial Colonization in Early Life

Extensive microbial colonization of the infant gastrointestinal tract starts after parturition. There are several parallel mechanisms by which early life microbiome acquisition may proceed, including early exposure to maternal vaginal and fecal microbiota, transmission of skin associated microbes, and ingestion of microorganisms present in breast milk. The crucial role of vertical transmission from the maternal microbial reservoir during vaginal delivery is supported by the shared microbial strains observed among mothers and their babies and the distinctly different gut microbiome composition of caesarean-section born infants. The healthy infant colon is often dominated by members of the keystone genus Bifidobacterium that have evolved complex genetic pathways to metabolize different glycans present in human milk. In exchange for these host-derived nutrients, bifidobacteria's saccharolytic activity results in an anaerobic and acidic gut environment that is protective against enteropathogenic infection. Interference with early-life microbiota acquisition and development could result in adverse health outcomes. Compromised microbiota development, often characterized by decreased abundance of Bifidobacterium species has been reported in infants delivered prematurely, delivered by caesarean section, early life antibiotic exposure and in the case of early life allergies. Various microbiome modulation strategies such as probiotic, prebiotics, synbiotics and postbiotics have been developed that are able to generate a bifidogenic shift and help to restore the microbiota development. This review explores the evolutionary ecology of early-life type Bifidobacterium strains and their symbiotic relationship with humans and discusses examples of compromised microbiota development in which stimulating the abundance and activity of Bifidobacterium has demonstrated beneficial associations with health

Early-life fecal microbiome and metabolome dynamics in response to an intervention with infant formula containing specific prebiotics and postbiotics

This study examined fecal metabolome dynamics to gain greater functional insights into the interactions between nutrition and the activity of the developing gut microbiota in healthy term-born infants. The fecal samples used here originate from a randomized, controlled, double-blind clinical study that assessed the efficacy of infant formula with prebiotics and postbiotics (experimental arm) compared with a standard infant formula (control arm). A group of exclusively breast-fed term infants was used as a reference arm. First, conventional targeted physiological and microbial measurements were performed, which showed differences in fecal Bifidobacterium levels and corresponding activity (e.g., lactate levels). Next, the overall fecal microbiota composition was determined by 16S rRNA gene amplicon sequencing. The microbiota composition profiles showed several bacterial groups in the experimental arm to be significantly different from the control arm and mostly closer to the levels observed in the reference arm. Finally, we applied an untargeted UPLC-MS/MS approach to examine changes in the fecal metabolome. Fecal metabolome profiles showed the most distinct separation, up to 404 significantly different metabolites, between the study arms. Our data reveal that infant formula with specific prebiotics and postbiotics may trigger responses in the intestinal microbiota composition that brings the ensuing fecal metabolite profile of formula-fed infants closer toward those observed in breast-fed infants. Furthermore, our results demonstrate a clear need for establishing an infant gut metabolome reference database to translate these metabolite profile dynamics into functional and physiologically relevant responses. NEW & NOTEWORTHY Untargeted metabolomics techniques can provide a ???snapshot??? of an ecosystem in response to environmental stimuli, such as nutritional interventions. Our analyses of fecal samples from infants demonstrate the potential of phenotyping by metabolomics while deciphering the complex interactions of early-life nutrition and gut microbiome development

The genome of the intracellular bacterium of the coastal bivalve, Solemya velum: a blueprint for thriving in and out of symbiosis

Background: Symbioses between chemoautotrophic bacteria and marine invertebrates are rare examples of living systems that are virtually independent of photosynthetic primary production. These associations have evolved multiple times in marine habitats, such as deep-sea hydrothermal vents and reducing sediments, characterized by steep gradients of oxygen and reduced chemicals. Due to difficulties associated with maintaining these symbioses in the laboratory and culturing the symbiotic bacteria, studies of chemosynthetic symbioses rely heavily on culture independent methods. The symbiosis between the coastal bivalve, Solemya velum, and its intracellular symbiont is a model for chemosynthetic symbioses given its accessibility in intertidal environments and the ability to maintain it under laboratory conditions. To better understand this symbiosis, the genome of the S. velum endosymbiont was sequenced. Results: Relative to the genomes of obligate symbiotic bacteria, which commonly undergo erosion and reduction, the S. velum symbiont genome was large (2.7 Mb), GC-rich (51%), and contained a large number (78) of mobile genetic elements. Comparative genomics identified sets of genes specific to the chemosynthetic lifestyle and necessary to sustain the symbiosis. In addition, a number of inferred metabolic pathways and cellular processes, including heterotrophy, branched electron transport, and motility, suggested that besides the ability to function as an endosymbiont, the bacterium may have the capacity to live outside the host. Conclusions: The physiological dexterity indicated by the genome substantially improves our understanding of the genetic and metabolic capabilities of the S. velum symbiont and the breadth of niches the partners may inhabit during their lifecycle. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-924) contains supplementary material, which is available to authorized users

Differential Modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids.

The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal organoids. We have explored the transcriptional response of organoids upon exposure to short-chain fatty acids (SCFAs) and products generated by two abundant microbiota constituents, Akkermansia muciniphila and Faecalibacterium prausnitzii. We observed that A. muciniphila metabolites affect various transcription factors and genes involved in cellular lipid metabolism and growth, supporting previous in vivo findings. Contrastingly, F. prausnitzii products exerted only weak effects on host transcription. Additionally, A. muciniphila and its metabolite propionate modulated expression of Fiaf, Gpr43, histone deacetylases (HDACs), and peroxisome proliferator-activated receptor gamma (Ppar¿), important regulators of transcription factor regulation, cell cycle control, lipolysis, and satiety. This work illustrates that specific bacteria and their metabolites differentially modulate epithelial transcription in mouse organoids. We demonstrate that intestinal organoids provide a novel and powerful ex vivo model for host-microbiome interaction studies

Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation:a randomised controlled trial

OBJECTIVE: Revised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants. DESIGN: In this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing. RESULTS: Compared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points. CONCLUSION: We confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health

Differential Modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids

Peer reviewe

Evidence for a core gut microbiota in the zebrafish

Experimental analysis of gut microbial communities and their interactions with vertebrate hosts is conducted predominantly in domesticated animals that have been maintained in laboratory facilities for many generations. These animal models are useful for studying coevolved relationships between host and microbiota only if the microbial communities that occur in animals in lab facilities are representative of those that occur in nature. We performed 16S rRNA gene sequence-based comparisons of gut bacterial communities in zebrafish collected recently from their natural habitat and those reared for generations in lab facilities in different geographic locations. Patterns of gut microbiota structure in domesticated zebrafish varied across different lab facilities in correlation with historical connections between those facilities. However, gut microbiota membership in domesticated and recently caught zebrafish was strikingly similar, with a shared core gut microbiota. The zebrafish intestinal habitat therefore selects for specific bacterial taxa despite radical differences in host provenance and domestication status