Postoperative changes of the microbiome: are surgical complications related to the gut flora? A systematic review

Background

The purpose of this review was to identify the relationship between the gut microbiome and the development of postoperative complications like anastomotic leakage or a wound infection. Recent reviews focusing on underlying molecular biology suggested that postoperative complications might be influenced by the patients’ gut flora. Therefore, a review focusing on the available clinical data is needed.

Methods

In January 2017 a systematic search was carried out in Medline and WebOfScience to identify all clinical studies, which investigated postoperative complications after gastrointestinal surgery in relation to the microbiome of the gut.

Results

Of 337 results 10 studies were included into this analysis after checking for eligibility. In total, the studies comprised 677 patients. All studies reported a postoperative change of the gut flora. In five studies the amount of bacteria decreased to different degrees after surgery, but only one study found a significant reduction. Surgical procedures tended to result in an increase of potentially pathogenic bacteria and a decrease of Lactobacilli and Bifidobacteria. The rate of infectious complications was lower in patients treated with probiotics/symbiotics compared to control groups without a clear relation to the systemic inflammatory response. The treatment with synbiotics/probiotics in addition resulted in faster recovery of bowel movement and a lower rate of postoperative diarrhea and abdominal cramping.

Conclusions

There might be a relationship between the gut flora and the development of postoperative complications. Due to methodological shortcomings of the included studies and uncontrolled bias/confounding factors there remains a high level of uncertainty.

     

Baclofen attenuates cue-induced reinstatement of alcohol-seeking behavior in Sardinian alcohol-preferring (sP) rats

The GABA_B receptor agonist, baclofen, suppressed alcohol deprivation effect (a proposed experimental model of alcohol relapse) in Sardinian alcohol-preferring rats. The present study was designed to extend the characterization of the “anti-relapse” properties of baclofen to the reinstatement of alcohol-seeking behavior (another proposed model of alcohol relapse). Rats of the sP line were first trained to lever press for alcohol under a fixed ratio 4 schedule of reinforcement. Subsequently, rats were exposed to two within-session 70-min extinction/reinstatement tests with saline or baclofen administered in a counterbalanced, within-subject design. After a 60-min extinction phase, an alcohol-associated stimulus complex was presented (reinstatement phase). Saline or baclofen (3 mg/kg) were administered via a permanent intraperitoneal catheter, 30 min before the reinstatement phase. During the reinstatement phase, baclofen administration: (a) reduced by approximately 60% responses on the previously active lever, (b) increased latency to the first response and (c) decreased the response rate. These results indicate that baclofen reduced cue-induced reinstatement of alcohol-seeking behavior in sP rats.     

Heterozygous CTNNB1 and TBX4 variants in a patient with abnormal lung growth,pulmonary hypertension,microcephaly, and spasticity

The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full-term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.     

Differential habituation to repeated sounds in infants at high risk for autism

It has been suggested that poor habituation to stimuli might explain atypical sensory behaviours in autism. We investigated habituation to repeated sounds using an oddball paradigm in 9-month-old infants with an older sibling with autism and hence at high risk for developing autism. Auditory-evoked responses to repeated sounds in control infants (at low risk of developing autism) decreased over time, demonstrating habituation, and their responses to deviant sounds were larger than responses to standard sounds, indicating discrimination. In contrast, neural responses in infants at high risk showed less habituation and a reduced sensitivity to changes in frequency. Reduced sensory habituation may be present at a younger age than the emergence of autistic behaviour in some individuals, and we propose that this could play a role in the over responsiveness to some stimuli and undersensitivity to others observed in autism.     

Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy

In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.