Evidence suggests that altered gut microbiota composition may be involved in the development of obesity. Studies using mice made obese with refined high-fat diets have supported this; however, these have commonly used chow as a control diet, introducing confounding factors from differences in dietary composition that have a key role in shaping microbiota composition. We compared the effects of feeding a refined high-fat diet with those of feeding either a refined low-fat diet or a chow diet on gut microbiota composition and host physiology. Feeding both refined low- or high-fat diets resulted in large alterations in the gut microbiota composition, intestinal fermentation, and gut morphology, compared to a chow diet. However, body weight, body fat, and glucose intolerance only increased in mice fed the refined high-fat diet. The choice of control diet can dissociate broad changes in microbiota composition from obesity, raising questions about the previously proposed relationship between gut microbiota and obesity.

Hypothalamic inflammation is thought to contribute to obesity. One potential mechanism is via gut microbiota derived bacterial lipopolysaccharide (LPS) entering into the circulation and activation of Toll-like receptor-4. This is called metabolic endotoxemia. Another potential mechanism is systemic inflammation arising from sustained exposure to high-fat diet (HFD) over more than 12 weeks. In this study we show that mice fed HFD over 8 weeks become obese and show elevated plasma LPS binding protein, yet body weight gain and adiposity is not attenuated in mice lacking Tlr4 or its co-receptor Cd14. In addition, caecal microbiota composition remained unchanged by diet. Exposure of mice to HFD over a more prolonged period (20 weeks) to drive systemic inflammation also caused obesity. RNAseq used to assess hypothalamic inflammation in these mice showed increased hypothalamic expression of Serpina3n and Socs3 in response to HFD, with few other genes altered. In situ hybridisation confirmed increased Serpina3n and Socs3 expression in the ARC and DMH at 20-weeks, but also at 8-weeks and increased SerpinA3N protein could be detected as early as 1 week on HFD. Overall these data show lack of hypothalamic inflammation in response to HFD and that metabolic endotoxemia does not link HFD to obesity.

As well as being vectors of many viral, bacterial, and protozoan pathogens of medical and veterinary importance, ticks harbour a variety of microorganisms which are not known to be pathogenic for vertebrate hosts. Continuous cell lines established from ixodid and argasid ticks could be infected with such endosymbiotic bacteria and endogenous viruses, but to date very few cell lines have been examined for their presence. DNA and RNA extracted from over 50 tick cell lines deposited in the Roslin Wellcome Trust Tick Cell Biobank (http://tickcells.roslin.ac.uk) were screened for presence of bacteria and RNA viruses, respectively. Sequencing of PCR products amplified using pan-16S rRNA primers revealed the presence of DNA sequences from bacterial endosymbionts in several cell lines derived from Amblyomma and Dermacentor spp. ticks. Identification to species level was attempted using Rickettsia- and Francisella-specific primers. Pan-Nairovirus primers amplified PCR products of uncertain specificity in cell lines derived from Rhipicephalus, Hyalomma, Ixodes, Carios, and Ornithodoros spp. ticks. Further characterisation attempted with primers specific for Crimean-Congo haemorrhagic fever virus segments confirmed the absence of this arbovirus in the cells. A set of pan-Flavivirus primers did not detect endogenous viruses in any of the cell lines. Transmission electron microscopy revealed the presence of endogenous reovirus-like viruses in many of the cell lines; only 4 of these lines gave positive results with primers specific for the tick Orbivirus St Croix River virus, indicating that there may be additional, as yet undescribed 'tick-only' viruses inhabiting tick cell lines.

Background: Bifidobacterium represents an important early life microbiota member. Specific bifidobacterial components, exopolysaccharides (EPS), positively modulate host responses, with purified EPS also suggested to impact microbe–microbe interactions by acting as a nutrient substrate. Thus, we determined the longitudinal effects of bifidobacterial EPS on microbial communities and metabolite profiles using an infant model colon system. Methods: Differential gene expression and growth characteristics were determined for each strain; Bifidobacterium breve UCC2003 and corresponding isogenic EPS-deletion mutant (B. breve UCC2003del). Model colon vessels were inoculated with B. breve and microbiome dynamics monitored using 16S rRNA sequencing and metabolomics (NMR). Results: Transcriptomics of EPS mutant vs. B. breve UCC2003 highlighted discrete differential gene expression (e.g., eps biosynthetic cluster), though overall growth dynamics between strains were unaffected. The EPS-positive vessel had significant shifts in microbiome and metabolite profiles until study end (405 h); with increases of Tyzzerella and Faecalibacterium, and short-chain fatty acids, with further correlations between taxa and metabolites which were not observed within the EPS-negative vessel. Conclusions: These data indicate that B. breve UCC2003 EPS is potentially metabolized by infant microbiota members, leading to differential microbial metabolism and altered metabolite by-products. Overall, these findings may allow development of EPS-specific strategies to promote infant health.

The neonatal developmental window represents a key time for establishment of the gut microbiota. First contact with these microbes within the infant gastrointestinal tract signifies the start of a critical mutualistic relationship, which is central for short- and longer-term health. Recent research has provided insights into the origin of these microbial pioneers, how they are maintained within the gut environment, and how factors such as antibiotics or preterm birth may disrupt the succession of beneficial microbes. The acquisition, colonisation, and maintenance of the early life microbiota, and subsequent interactions with the host is a rapidly developing research area. In this review we explore some of these key topics which have been illuminated by recent research, and we highlight some of the important unresolved questions which currently limit our overall understanding of the neonatal gut microbiome.

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g,n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probioticBifidobacterium longumsubsp.infantisNCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probioticLactobacillus rhamnosusLCR 35 or no supplementation. Crucially, the beneficial effects ofBifidobacterium longumsubsp.infantisNCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.