A maternal high-fat diet predisposes to infant lung disease via increased neutrophil-mediated IL-6 trans-signaling.

A poor maternal diet during pregnancy predisposes the infant to severe lower respiratory tract infections (sLRIs), which, in turn, increases childhood asthma risk; however, the underlying mechanisms remain poorly understood. Here, we show that the offspring of high-fat diet (HFD)-fed mothers (HFD-reared pups) developed an sLRI following pneumovirus inoculation in early life and subsequent asthma in later life upon allergen exposure. Prior to infection, HFD-reared pups developed microbial dysbiosis and low-grade systemic inflammation (LGSI), characterized by hyperneutropoiesis in the liver and elevated inflammatory cytokine expression, most notably granulocyte-colony stimulating factor (G-CSF), interleukin-17A (IL-17A), IL-6 and soluble IL-6 receptor (sIL-6R) (indicative of IL-6 trans-signaling) in the circulation and multiple organs but most prominently the liver.

Draft genome sequence of two "Candidatus Intestinicoccus colisanans" strains isolated from faeces of healthy humans.

Objectives: In order to provide a better insight into the functional capacity of the human gut microbiome, we isolated a novel bacterium, "Candidatus Intestinicoccus colisanans" gen. nov. sp.

Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection.

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome.

Secreted NF-κB suppressive microbial metabolites modulate gut inflammation.

Emerging evidence suggests that microbiome-host crosstalk regulates intestinal immune activity and predisposition to inflammatory bowel disease (IBD). NF-κB is a master regulator of immune function and a validated target for the treatment of IBD. Here, we identify five Clostridium strains that suppress immune-mediated NF-κB activation in epithelial cell lines, PBMCs, and gut epithelial organoids from healthy human subjects and patients with IBD.

Standard rectal swabs as a surrogate sample for gut microbiome monitoring in intensive care.

Background: The purpose of this study was to investigate the use of routinely available rectal swabs as a surrogate sample type for testing the gut microbiome and monitoring antibiotic effects on key gut microorganisms, of patients hospitalised in an intensive care unit. A metagenomic whole genome sequencing approach was undertaken to determine the diversity of organisms as well as resistance genes and to compare findings between the two sampling techniques.

Results: No significant difference was observed in overall diversity between the faeces and rectal swabs and sampling technique was not demonstrated to predict microbial community variation.

Successful Manipulation of the Gut Microbiome to Treat Spontaneous and Induced Murine Models of Colitis.

Background And Aims: There is clinical interest in the sustainability or otherwise of prebiotic, microbial, and antibiotic treatments to both prevent and treat inflammatory bowel diseases. This study examined the role of antibiotic manipulation of the gut microbiome to treat spontaneous and induced murine models of colitis.

Methods: Symptomatic, histological, molecular, and microbial ecology and bioinformatic readouts were used to study the effect of a 10-day antibiotic cocktail and then follow-up over 2 months in the spontaneous Winnie colitis mouse preclinical model of ulcerative colitis and also the indirect antibiotic and Winnie microbiotic gavage effects in an acute dextran sodium sulfate-induced colitis model in wild-type mice.

species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice.

Objectives: Analysis of oral dysbiosis in individuals sharing genetic and environmental risk factors with rheumatoid arthritis (RA) patients may illuminate how microbiota contribute to disease susceptibility. We studied the oral microbiota in a prospective cohort of patients with RA, first-degree relatives (FDR) and healthy controls (HC), then genomically and functionally characterised streptococcal species from each group to understand their potential contribution to RA development.

Methods: After DNA extraction from tongue swabs, targeted 16S rRNA gene sequencing and statistical analysis, we defined a microbial dysbiosis score based on an operational taxonomic unit signature of disease.

Culture- and metagenomics-enabled analyses of the Methanosphaera genus reveals their monophyletic origin and differentiation according to genome size.

The genus Methanosphaera is a well-recognized but poorly characterized member of the mammalian gut microbiome, and distinctive from Methanobrevibacter smithii for its ability to induce a pro-inflammatory response in humans. Here we have used a combination of culture- and metagenomics-based approaches to expand the representation and information for the genus, which has supported the examination of their phylogeny and physiological capacity. Novel isolates of the genus Methanosphaera were recovered from bovine rumen digesta and human stool, with the bovine isolate remarkable for its large genome size relative to other Methanosphaera isolates from monogastric hosts.

Food Starch Structure Impacts Gut Microbiome Composition.

Starch is a major source of energy in the human diet and is consumed in diverse forms. Resistant starch (RS) escapes small intestinal digestion and is fermented in the colon by the resident microbiota, with beneficial impacts on colonic function and host health, but the impacts of the micro- and nanoscale structure of different physical forms of food starch on the broader microbial community have not been described previously. Here, we use a porcine fermentation model to establish that starch structure dramatically impacts microbiome composition, including the key amylolytic species, and markedly alters both digestion kinetics and fermentation outcomes.

AHG0090 is a Genetically Tractable Bacterium and Produces a Secreted Peptidic Bioactive that Suppresses Nuclear Factor Kappa B Activation in Human Gut Epithelial Cells.

is an early coloniser of the human infant gut and contributes to the development of intestinal immunity. To better understand the functional capacity of , we constructed a broad host range RP4 mobilizable vector, pEHR513112, that confers chloramphenicol resistance and used a metaparental mating approach to isolate AHG0090 from a fecal sample collected from a healthy human infant. We demonstrated that AHG0090 is genetically tractable and could be manipulated using traditional molecular microbiology approaches.

Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a-mediated T reg expansion.

Respiratory syncytial virus-bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1 regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a).

Colonic thioguanine pro-drug: Investigation of microbiome and novel host metabolism.

Thiopurines are analogues of endogenous purines. They are pro-drugs which require the purine salvage pathway to convert them to the active drug nucleotides (TGN). These drugs are used to maintain clinical remission in patients with inflammatory bowel diseases.

The gut bacterium and pathobiont Bacteroides vulgatus activates NF-κB in a human gut epithelial cell line in a strain and growth phase dependent manner.

The gut microbiota is increasingly implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) although the identity of the bacteria that underpin these diseases has remained elusive. The pathobiont Bacteroides vulgatus has been associated with both diseases although relatively little is known about how its growth and functional activity might drive the host inflammatory response. We identified an ATP Binding Cassette (ABC) export system and lipoprotein in B.

The Influence of the Microbiome on Early-Life Severe Viral Lower Respiratory Infections and Asthma-Food for Thought?

Severe viral lower respiratory infections are a major cause of infant morbidity. In developing countries, respiratory syncytial virus (RSV)-bronchiolitis induces significant mortality, whereas in developed nations the disease represents a major risk factor for subsequent asthma. Susceptibility to severe RSV-bronchiolitis is governed by gene-environmental interactions that affect the host response to RSV infection.

Diet and the Microbiome.

The gut microbiota provides a range of ecologic, metabolic, and immunomodulatory functions relevant to health and well-being. The gut microbiota not only responds quickly to changes in diet, but this dynamic equilibrium may be managed to prevent and/or treat acute and chronic diseases. This article provides a working definition of the term "microbiome" and uses two examples of dietary interventions for the treatment of large bowel conditions to emphasize the links between diet and microbiome.

Microbial metabolism of thiopurines: A method to measure thioguanine nucleotides.

Thiopurines are anti-inflammatory prodrugs. We hypothesised that bacteria may contribute to conversion to active drug. Escherichia coli strain DH5α was evaluated to determine whether it could metabolise the thiopurine drugs, thioguanine or mercaptopurine, to thioguanine nucleotides.

High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation that is Reversed by IL-22.

Prolonged high fat diets (HFD) induce low-grade chronic intestinal inflammation in mice, and diets high in saturated fat are a risk factor for the development of human inflammatory bowel diseases. We hypothesized that HFD-induced endoplasmic reticulum (ER)/oxidative stress occur in intestinal secretory goblet cells, triggering inflammatory signaling and reducing synthesis/secretion of proteins that form the protective mucus barrier. In cultured intestinal cells non-esterified long-chain saturated fatty acids directly increased oxidative/ER stress leading to protein misfolding.

Differences down-under: alcohol-fueled methanogenesis by archaea present in Australian macropodids.

The Australian macropodids (kangaroos and wallabies) possess a distinctive foregut microbiota that contributes to their reduced methane emissions. However, methanogenic archaea are present within the macropodid foregut, although there is scant understanding of these microbes. Here, an isolate taxonomically assigned to the Methanosphaera genus (Methanosphaera sp.

Towards an integrated understanding of the therapeutic utility of exclusive enteral nutrition in the treatment of Crohn's disease.

Crohn's disease (CD) is a chronic disease characterized by episodic and disabling inflammation of the gastrointestinal tract in genetically susceptible individuals. The incidence and prevalence of CD is rising rapidly across the world emphasising that disease risk is also influenced by environmental and lifestyle factors, as well as the microbial community resident in the gut. Childhood-onset CD is associated with an aggressive disease course that can adversely impact patient growth and development.

Isolation of Genetically Tractable Most-Wanted Bacteria by Metaparental Mating.

Metagenomics has rapidly advanced our inventory and appreciation of the genetic potential inherent to the gut microbiome. However it is widely accepted that two key constraints to further genetic dissection of the gut microbiota and host-microbe interactions have been our inability to recover new isolates from the human gut, and the paucity of genetically tractable gut microbes. To address this challenge we developed a modular RP4 mobilisable recombinant vector system and an approach termed metaparental mating to support the rapid and directed isolation of genetically tractable fastidious gut bacteria.

Draft Genome Sequence of Enterococcus faecium PC4.1, a Clade B Strain Isolated from Human Feces.

Enterococcus faecium is commonly isolated from the human gastrointestinal tract; however, important intraspecies variations exist with relevance for host health and well-being. Here, we describe the draft genome sequence of E. faecium PC4.

Extending the cellulosome paradigm: the modular Clostridium thermocellum cellulosomal serpin PinA is a broad-spectrum inhibitor of subtilisin-like proteases.

Clostridium thermocellum encodes a cellulosomal, modular, and thermostable serine protease inhibitor (serpin), PinA. PinA stability but not inhibitory activity is affected by the Fn(III) and Doc(I) domains, and PinA is a broad inhibitor of subtilisin-like proteases and may play a key role in protecting the cellulosome from protease attack.

Genome Sequence of Stenotrophomonas maltophilia Strain AU12-09, Isolated from an Intravascular Catheter.

Stenotrophomonas maltophilia is an opportunistic nosocomial pathogen that is characterized by its high-level intrinsic resistance to a variety of antibiotics and its ability to form biofilms. Here, we report the draft genome sequence of Stenotrophomonas maltophilia AU12-09, isolated from an intravascular catheter tip.

Draft Genome Sequence of Enterococcus faecalis PC1.1, a Candidate Probiotic Strain Isolated from Human Feces.

is commonly isolated from the gastrointestinal tract of healthy infants and adults, where it contributes to host health and well-being. We describe here the draft genome sequence of PC1.1, a candidate probiotic strain isolated from human feces.

Genome sequence of Staphylococcus epidermidis strain AU12-03, isolated from an intravascular catheter.

In recent years, Staphylococcus epidermidis has become a major nosocomial pathogen and the most common cause of intravascular catheter-related bacteremia, which can increase morbidity and mortality and significantly affect patient recovery. We report a draft genome sequence of Staphylococcus epidermidis AU12-03, isolated from an intravascular catheter tip.