Intestinal dysbiosis as an intraoperative predictor of septic complications: evidence from human surgical cohorts and preclinical models of peritoneal sepsis.

Major surgery exposes the intestinal microbiota to inflammatory and antibiotic stressors, which alter the microbiota composition of the intestinal lumen and fecal contents. However, it is not sufficiently understood, if such dysbiosis develops already during surgery and if alterations in microbiota may be the cause of surgical complications. End-of-surgery composition of the microbiota in the rectum was assessed in 41 patients undergoing either rectal or duodenopancreatic resection and was compared to baseline before surgery using 16S-rRNA sequencing. A subset of patients developed severe dysbiosis at the end of surgery, which was characterized by an overgrowth of the Proteobacteria phylum that includes the facultative pathogen E. coli. To test if dysbiosis impacts on surgical outcomes, dysbiosis was modeled in mice by a single oral administration of vancomycin prior to cecal ligation and puncture. Dysbiosis was associated with impaired post-surgical survival, dysregulation of the host's immune response, elevated bacterial virulence and reduced bacterial metabolism of carbon sources. In conclusion, dysbiosis can be detected already at the end of surgery in a fraction of patients undergoing major surgery. Modelling surgery-associated dysbiosis in mice using single-shot administration of vancomycin induced dysbiosis and resulted in elevated mortality.

ILC3s restrict the dissemination of intestinal bacteria to safeguard liver regeneration after surgery.

It is generally believed that environmental or cutaneous bacteria are the main origin of surgical infections. Therefore, measures to prevent postoperative infections focus on optimizing hygiene and improving asepsis and antisepsis. In a large cohort of patients with infections following major surgery, we identified that the causative bacteria are mainly of intestinal origin. Postoperative infections of intestinal origin were also found in mice undergoing partial hepatectomy. CCR6+ group 3 innate lymphoid cells (ILC3s) limited systemic bacterial spread. Such bulwark function against host invasion required the production of interleukin-22 (IL-22), which controlled the expression of antimicrobial peptides in hepatocytes, thereby limiting bacterial spread. Using genetic loss-of-function experiments and punctual depletion of ILCs, we demonstrate that the failure to restrict intestinal commensals by ILC3s results in impaired liver regeneration. Our data emphasize the importance of endogenous intestinal bacteria as a source for postoperative infection and indicate ILC3s as potential new targets.

Plasticity of the adult human small intestinal stoma microbiota.

The human distal small intestine (ileum) has a distinct microbiota, but human studies investigating its composition and function have been limited by the inaccessibility of the ileum without purging and/or deep intubation. We investigated inherent instability, temporal dynamics, and the contribution of fed and fasted states using stoma samples from cured colorectal cancer patients as a non-invasive access route to the otherwise inaccessible small and large intestines. Sequential sampling of the ileum before and after stoma formation indicated that ileostoma microbiotas represented that of the intact small intestine. Ileal and colonic stoma microbiotas were confirmed as distinct, and two types of instability in ileal host-microbial relationships were observed: inter-digestive purging followed by the rapid postprandial blooming of bacterial biomass and sub-strain appearance and disappearance within individual taxa after feeding. In contrast to the relative stability of colonic microbiota, the human small intestinal microbiota biomass and its sub-strain composition can be highly dynamic.

Regular testing of asymptomatic healthcare workers identifies cost-efficient SARS-CoV-2 preventive measures.

Protecting healthcare professionals is crucial in maintaining a functioning healthcare system. The risk of infection and optimal preventive strategies for healthcare workers during the COVID-19 pandemic remain poorly understood. Here we report the results of a cohort study that included pre- and asymptomatic healthcare workers. A weekly testing regime has been performed in this cohort since the beginning of the COVID-19 pandemic to identify infected healthcare workers. Based on these observations we have developed a mathematical model of SARS-CoV-2 transmission that integrates the sources of infection from inside and outside the hospital. The data were used to study how regular testing and a desynchronisation protocol are effective in preventing transmission of COVID-19 infection at work, and compared both strategies in terms of workforce availability and cost-effectiveness. We showed that case incidence among healthcare workers is higher than would be explained solely by community infection. Furthermore, while testing and desynchronisation protocols are both effective in preventing nosocomial transmission, regular testing maintains work productivity with implementation costs.

Extracellular ATP as an Inter-Kingdom Signaling Molecule: Release Mechanisms by Bacteria and Its Implication on the Host.

The purine adenosine 5'-triphosphate (ATP) is not only a universal intracellular energy carrier but plays also an important role as extracellular signaling molecule. Purinergic signaling is involved in many physiological and pathological processes like coagulation, inflammation, or sepsis in mammals. ATP is well-known as a messenger for intercellular communications in multicellular organisms, but phylogenetically much older unicellular organisms like yeast or bacteria use ATP as an extracellular signaling molecule as well. However, the mechanisms of ATP secretion by bacteria and its extracellular implications still have to be elucidated. This review will provide an overview of the current knowledge about bacterial extracellular ATP (eATP) under homeostatic conditions and during growth. Possible secretion mechanisms of ATP by bacteria will be discussed and implications of bacterial ATP are shown, with a focus on bacteria-host interactions.

Prophylactic, Synthetic Intraperitoneal Mesh Versus No Mesh Implantation in Patients with Fascial Dehiscence.

BACKGROUND: Primary closure of post-operative facial dehiscence (FD) is associated with a high incidence of recurrence, revisional surgery, and incisional hernia. This retrospective study compares outcomes of implantation of non-absorbable intra-abdominal meshes with primary closure of FD. The outcomes of different mesh materials were assessed in subgroup analysis. METHODS: A total of 119 consecutive patients with FD were operated (70 mesh group and 49 no mesh group) between 2001 and 2015. Primary outcome parameter was hernia-free survival. Secondary outcome parameters include re-operations of the abdominal wall, intestinal fistula, surgical site infections (SSI), and mortality. Kaplan-Meier analysis for hernia-free survival, adjusted Poisson regression analysis for re-operations and adjusted regression analysis for chronic SSI was performed. RESULTS: Hernia-free survival was significantly higher in the mesh group compared to the no mesh group (P = 0.005). Fewer re-operations were necessary in the mesh group compared to the no mesh group (adjusted incidence risk ratio 0.44, 95% confidence interval [CI] 0.20-0.93, P = 0.032). No difference in SSI, intestinal fistula, and mortality was observed between groups. Chronic SSI was observed in 7 (10%) patients in the mesh group (n = 3 [6.7%] with polypropylene mesh and 4 [28.6%] with polyester mesh). The risk for chronic SSI was significantly higher if a polyester mesh was used when compared to a polypropylene mesh (adjusted odds ratio 8.69, 95% CI 1.30-58.05, P = 0.026). CONCLUSION: Implantation of a polypropylene but not polyester-based mesh in patients with FD decreases incisional hernia with a low rate of mesh-related morbidity.