Purpose
Gestational diabetes mellitus (GDM), the major endocrine pathology in pregnancy, has been associated with the development of an intense inflammatory process and increased insulin resistance. ...The maternal microbiota is involved in several metabolic functions; however, its role in GDM physiopathology remains unclear. The aim of this study was to assess the composition of the microbiota at different sites and evaluate its relationship with the occurrence of GDM.
Methods
This cross-sectional study recruited women in the third trimester of gestation with and without GDM. Oral, vaginal, and stool samples were evaluated using next-generation sequencing. We included 68 participants: 26 with and 42 without GDM.
Results
The analysis of the oral microbiome did not show significant differences in phyla and genus among the studied groups. In contrast, GDM patients presented a specific vaginal and intestinal microbiome composition, which was less diverse than those found in the control group, showing genera related to dysbiosis.
Conclusions
Our findings suggest that changes in the composition of the vaginal and intestinal microbiome might be involved in the development of GDM. The follow-up of these patients in order to evaluate vaginal and intestinal samples after delivery may contribute to understanding the development of metabolic disease in women with previous GDM.
The objective of this prospective study is to determine cognitive dysfunction after thoracic surgery.
Seventy-six patients undergoing thoracic surgery with single-lung ventilation (SLV) of an ...expected duration of >45 min were enrolled. Monitoring consisted of standard clinical parameters and absolute oximetry (SctO2). The Mini-Mental State Exam (MMSE) test was used to assess cognitive function before operation and at 3 and 24 h after operation. Data were analysed using Spearman correlation test; risks for cognitive dysfunction were expressed as odds ratios. P<0.05 and data are presented as median (interquartile range).
One patient was excluded from the study. SctO2 during SLV decreased to critical values of <65%, 60%, and 55% in 40 (53%), 15 (20%), and 5 patients (7%), respectively. Twenty-two patients (29%) had a decrease of MMSE>2 points 3 h after surgery, eight patients (10%) had a decrease of MMSE>2 points 24 h after surgery. Postoperative cognitive dysfunction correlated at r2=0.272, 0.285, 0.297 with patient exposure times to SctO2<65% (P=0.018), <60% (P=0.013), <55% (P=0.010), respectively. The odds ratios of developing early cognitive dysfunction ranged from 2.03 (95% CI: 0.74–5.59) for a short (<5 min) exposure to SctO2<65% to a maximum of 9.56 (95% CI: 1.75–52.13) when SctO2 was <60% for more than 30 min.
Early cognitive dysfunction after thoracic surgery with SLV is positively related to intraoperative decline of SctO2.
Very low birth weight (VLBW) infants, mostly preterm, have many barriers to feeding directly from the mother's breast, and need to be fed alternatively. Feeding is a major influencer in oral ...microbial colonization, and this colonization in early life is crucial for the promotion of human health. Therefore, this research aimed to observe the establishment of oral microbiome in VLBW infants during their first month of life through hospitalization, and to verify the impact caused by the implementation of oral diet on the colonization of these newborns. We included 23 newborns followed during hospitalization and analyzed saliva samples collected weekly, using 16S rRNA gene sequencing. We observed a significant decrease in richness and diversity and an increase in dominance over time (q-value < 0.05). The oral microbiome is highly dynamic during the first weeks of life, and beta diversity suggests a microbial succession in early life. The introduction of oral diet does not change the community structure, but affects the abundance, especially of Streptococcus. Our results indicate that although time is related to significant changes in the oral microbial profile, oral feeding benefits genera that will remain colonizers throughout the host's life.
The ability to adhere and adapt to the human respiratory tract mucosa plays a pivotal role in the pathogenic lifestyle of nontypeable Haemophilus influenzae (NTHi). However, the temporal events ...associated with a successful colonization have not been fully characterized. In this study, by reconstituting the ciliated human bronchial epithelium in vitro, we monitored the global transcriptional changes in NTHi and infected mucosal epithelium simultaneously for up to 72 h by dual RNA sequencing. The initial stage of colonization was characterized by the binding of NTHi to ciliated cells. Temporal profiling of host mRNA signatures revealed significant dysregulation of the target cell cytoskeleton elicited by bacterial infection, with a profound effect on the intermediate filament network and junctional complexes. In response to environmental stimuli of the host epithelium, NTHi downregulated its central metabolism and increased the expression of transporters, indicating a change in the metabolic regime due to the availability of host substrates. Concurrently, the oxidative environment generated by infected cells instigated bacterial expression of stress-induced defense mechanisms, including the transport of exogenous glutathione and activation of the toxin-antitoxin system. The results of this analysis were validated by those of confocal microscopy, Western blotting, Bio-plex, and real-time quantitative reverse transcription-PCR (qRT-PCR). Notably, as part of our screening for novel signatures of infection, we identified a global profile of noncoding transcripts that are candidate small RNAs (sRNAs) regulated during human host infection in Haemophilus species. Our data, by providing a robust and comprehensive representation of the cross talk between the host and invading pathogen, provides important insights into NTHi pathogenesis and the development of efficacious preventive strategies.
Simultaneous monitoring of infection-linked transcriptome alterations in an invading pathogen and its target host cells represents a key strategy for identifying regulatory responses that drive pathogenesis. In this study, we report the progressive events of NTHi colonization in a highly differentiated model of ciliated bronchial epithelium. Genome-wide transcriptome maps of NTHi during infection provided mechanistic insights into bacterial adaptive responses to the host niche, with modulation of the central metabolism as an important signature of the evolving milieu. Our data indicate that infected epithelia respond by substantial alteration of the cytoskeletal network and cytokine repertoire, revealing a dynamic cross talk that is responsible for the onset of inflammation. This work significantly enhances our understanding of the means by which NTHi promotes infection on human mucosae and reveals novel strategies exploited by this important pathogen to cause invasive disease.
Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to ...epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.
Exclusive breastfeeding promotes beneficial modifications on the microbiota of cesarean born infants, but little is known about the role of specific breast milk components in this modulation. Women ...with an active FUT2 gene (called secretors) secrete α1-2 fucosylated human milk oligosaccharides (HMOs), which promote Bifidobacterium in the infant's gut and may modulate the microbiota of cesarean born infants.
To compare the microbiota composition of cesarean and vaginally born infants breastfed by secretor mothers.
Maternal secretor status was determined by the occurrence of 4 different α1-2 fucosylated HMOs in breast milk by LC-MS. The fecal microbiota composition from cesarean and vaginally born infants was analyzed by 16S rRNA gene sequencing and qPCR, stratified by the maternal secretor status, and compared.
Alpha and beta diversity were not significantly different in cesarean born, secretor-fed infants (CSe+) compared to vaginally born, secretor-fed infants (VSe+). There were no significant differences in the fecal relative abundance of Bifidobacterium between CSe+ and VSe+ infants, but the prevalence of the species B. longum was lower in CSe+. The fecal relative abundance of Bacteroides was also lower, while Akkermansia and Kluyvera were higher in CSe+ infants.
Cesarean and vaginally born infants fed with breast milk containing the α1-2 fucosylated HMOs fraction present similar amounts of Bifidobacterium in the feces, but differences are observed in other members of the microbiota.
Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this ...cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of
and
genera were increased depending on patients' age at diagnosis.
was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of
in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.
Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of 7 transmembrane receptors mediating a wide variety of extracellular signals. We ...show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single-cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is up-regulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here, it controls oxygen consumption, cell proliferation, and the formation of reactive oxygen species (ROS) by reducing oxidative phosphorylation. Crispr/Cas9 editing of the key methionine where cap-independent translation begins in human-induced pluripotent stem cells (hiPSCs), reveals the physiological role of this process in influencing cell proliferation and oxygen consumption at the endogenous level. The expression of the C-terminal domain of a GPCR, capable of regulating mitochondrial function, constitutes a hitherto unknown mechanism notably unrelated to its canonical signaling function as a GPCR at the plasma membrane. This work thus highlights a potential novel mechanism that cells may use for controlling their metabolism under variable environmental conditions, notably as a negative regulator of cell respiration.
We have developed an automatic anaesthesia system for closed-loop administration of anaesthesia drugs. The control variables used were bispectral index (BIS) and Analgoscore for hypnosis and ...antinociception, respectively.
One hundred and eighty-six patients were randomly enrolled in two groups. Propofol, remifentanil, and rocuronium were administered using closed-loop feedback control (closed-loop, n = 93) or manually (control group, n = 93). The clinical performance of hypnosis control was determined by calculating the offset from a BIS of 45: ‘excellent', ‘good', ‘poor', and ‘inadequate' control was defined as BIS values within 10%, from 11% to 20%, from 21% to 30%, or >30% offset from the target. The clinical performance of analgesia was defined as the offset from Analgoscore values. Data presented as mean (standard deviation) (95% confidence interval).
Excellent or good control of hypnosis was achieved significantly longer in the closed-loop group 47.0 (9.8%) (45.0/49.0), 34.4 (4.7%) (33.5/35.4) than in the control group 37.3 (14.3%) (34.4/40.2) and 32.3 (7.6%) (30.7/33.7), respectively (P<0.0001 and 0.0085). Poor and inadequate control of hypnosis was significantly shorter in the closed-loop group 10.8 (5.0%) (9.8/11.8) and 7.7 (6.2%) (6.4/9.0) than in the control group 14.7 (6.8%) (13.3/16.0) and 15.8 (14.7%) (12.8/18.8), respectively (P<0.0001). Excellent control of analgesia was achieved significantly longer in the closed-loop group 78.7 (16.2%) (75.4/82.0) than in the control group 73.7 (17.8%) (70.1/77.3) (P=0.0456).
The closed-loop system was better at maintaining BIS and Analgoscore than manual administration.
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