Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity

Background Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated. Methods To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (n = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n = 27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level. Results Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control. Conclusion We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality

Prospective observational study of vaginal microbiota pre- and post-rescue cervical cerclage

Objective To investigate the relation between vaginal microbiota composition and outcome of rescue cervical cerclage. Design Prospective observational study. Setting Queen Charlotte's and Chelsea Hospital, London. Population Twenty singleton pregnancies undergoing a rescue cervical cerclage. Methods Vaginal microbiota composition was analysed in women presenting with a dilated cervix and exposed fetal membranes before and 10 days following rescue cervical cerclage and was correlated with clinical outcomes. Main outcome measures Composition of vaginal bacteria was characterised by culture‐independent next generation sequencing. Successful cerclage was defined as that resulting in the birth of a neonate discharged from hospital without morbidity. Unsuccessful cerclage was defined as procedures culminating in miscarriage, intrauterine death, neonatal death or significant neonatal morbidity. Results Reduced Lactobacillus spp. relative abundance was observed in 40% of cases prior to rescue cerclage compared with 10% of gestation age‐matched controls (8/20, 40% versus 3/30, 10%, P = 0.017). Gardnerella vaginalis was over‐represented in women presenting with symptoms (3/7, 43% versus 0/13, 0%, P = 0.03, linear discriminant analysis, LDA (log 10) and cases culminating in miscarriage (3/6, 50% versus 0/14, 0%, P = 0.017). In the majority of cases (10/14, 71%) bacterial composition was unchanged following cerclage insertion and perioperative interventions. Conclusions Reduced relative abundance of Lactobacillus spp. is associated with premature cervical dilation, whereas high levels of G. vaginalis are associated with unsuccessful rescue cerclage cases. The insertion of a rescue cerclage does not affect the underlying bacterial composition in the majority of cases

Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3-10 years: randomised controlled trial

In a double-blind, randomised, parallel-group, placebo-controlled study, healthy school children aged 3-10 years received a probiotic based supplement daily for 6 months to assess the impact on the incidence and duration of upper respiratory tract infection (URTI) symptoms. The intervention comprised Lab4 probiotic (Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) at 12.5 billion cfu/day plus 50 mg vitamin C or a matching placebo. 171 children were included in the analysis (85 in placebo and 86 in active group). Incidence of coughing was 16% (P=0.0300) significantly lower in the children receiving the active intervention compared to the placebo. No significant differences in the incidence rate of other URTI symptoms were observed. There was significantly lower risk of experiencing five different URTI related symptoms in one day favouring the active group (Risk ratio: 0.31, 95% confidence interval: 0.12, 0.81, P=0.0163). Absenteeism from school and the use of antibiotics was also significantly reduced for those in the active group (-16%, P=0.0060 and -27%, P=0.0203, respectively). Our findings indicate that six months daily supplementation with the Lab4 probiotic and vitamin C combination reduces the incidence of coughing, absenteeism and antibiotic usage in 3 to 10 year old children

The NuSTAR Serendipitous Survey: Hunting for the Most Extreme Obscured AGN at >10 keV

We identify sources with extremely hard X-ray spectra (i.e., with photon indices of ${\rm{\Gamma }}\lesssim 0.6$) in the 13 deg2 NuSTAR serendipitous survey, to search for the most highly obscured active galactic nuclei (AGNs) detected at $\gt 10\,\mathrm{keV}$. Eight extreme NuSTAR sources are identified, and we use the NuSTAR data in combination with lower-energy X-ray observations (from Chandra, Swift XRT, and XMM-Newton) to characterize the broadband (0.5–24 keV) X-ray spectra. We find that all of the extreme sources are highly obscured AGNs, including three robust Compton-thick (CT; ${N}_{{\rm{H}}}\gt 1.5\times {10}^{24}$ cm−2) AGNs at low redshift ($z\lt 0.1$) and a likely CT AGN at higher redshift (z = 0.16). Most of the extreme sources would not have been identified as highly obscured based on the low-energy ($\lt 10$ keV) X-ray coverage alone. The multiwavelength properties (e.g., optical spectra and X-ray–mid-IR luminosity ratios) provide further support for the eight sources being significantly obscured. Correcting for absorption, the intrinsic rest-frame 10–40 keV luminosities of the extreme sources cover a broad range, from $\approx 5\times {10}^{42}$ to 1045 erg s−1. The estimated number counts of CT AGNs in the NuSTAR serendipitous survey are in broad agreement with model expectations based on previous X-ray surveys, except for the lowest redshifts ($z\lt 0.07$), where we measure a high CT fraction of ${f}_{\mathrm{CT}}^{\mathrm{obs}}={30}_{-12}^{+16} \%$. For the small sample of CT AGNs, we find a high fraction of galaxy major mergers (50% ± 33%) compared to control samples of "normal" AGNs