Influence of the bile acid/microbiota axis in ileal surgery: a systematic review.

AIM: The gastrointestinal bile acid (BA)/microbiota axis has emerged as a potential mediator of health and disease, particularly in relation to pathologies such as inflammatory bowel disease (IBD) and colorectal cancer. Whilst it presents an exciting new avenue for therapies, it has not yet been characterized in surgical resection of the ileum, where BA reabsorption occurs. The identification of BA/microbiota signatures may provide future therapies with perioperative personalized medicine. In this work we conduct a systematic review with the aim of investigating the microbiome and BA changes that are associated with resection of the ileum. METHOD: The databases included were MEDLINE, EMBASE, Web of Science and Cochrane libraries. The outcomes of interest were faecal microbiome and BA signatures after ileal resection. RESULTS: Of the initial 3106 articles, three studies met the inclusion/exclusion criteria for data extraction. A total of 257 patients (46% surgery, 54% nonsurgery controls) were included in the three studies. Two studies included patients with short bowel syndrome and the other included patients with IBD. Large-scale microbiota changes were reported. In general, alpha diversity had decreased amongst patients with ileal surgery. Phylum-level changes included decreased Bacteroidetes and increased Proteobacteria and Fusobacteria in patients with an intestinal resection. Surgery was associated with increased total faecal BAs, cholic acid and chenodeoxycholic acid. There were decreases in deoxycholic acid and glycine and taurine conjugated bile salts. Integrated BA and microbiota data identified correlations with several bacterial families and BA. CONCLUSION: The BA/microbiota axis is still a novel area with minimal observational data in surgery. Further mechanistic research is necessary to further explore this and identify its role in improving perioperative outcomes.

Platelet activating factor receptor acts to limit colitis-induced liver inflammation.

Liver inflammation is a common extraintestinal manifestation in inflammatory bowel disease (IBD), yet, the mechanisms driving gut-liver axis inflammation remain poorly understood. IBD leads to a breakdown in the integrity of the intestinal barrier causing an increase in portal and systemic gut-derived antigens, which challenge the liver. Here, we examined the role of platelet activating factor receptor (PAFR) in colitis-associated liver damage using dextran sulfate sodium (DSS) and anti-CD40-induced colitis models. Both DSS and anti-CD40 models exhibited liver inflammation associated with colitis. Colitis reduced global PAFR protein expression in mouse livers causing an exclusive re-localization of PAFR to the portal triad. The global decrease in liver PAFR was associated with increased sirtuin 1 while relocalized PAFR expression was limited to Kupffer cells (KCs) and co-localized with toll-like receptor 4. DSS activated the NLRP3-inflammasome and increased interleukin (IL)-1ß in the liver. Antagonism of PAFR amplified the inflammasome response by increasing NLRP3, caspase-1, and IL-1ß protein levels in the liver. LPS also increased NLRP3 response in human hepatocytes, however, overexpression of PAFR restored the levels of NLPR3 and caspase-1 proteins. Interestingly, KCs depletion also increased IL-1ß protein in mouse liver after DSS challenge. These data suggest a protective role for PAFR-expressing KCs during colitis and that regulation of PAFR is important for gut-liver axis homeostasis.

Systematic Review on the Influence of Tissue Oxygenation on Gut Microbiota and Anastomotic Healing.

BACKGROUND: Anastomotic leak rates have not improved over several decades despite improvements in surgical techniques and patient care. The gut microbiome has been implicated in the development of leaks. The exact mechanisms by which tissue oxygenation affects gut microbial composition and anastomotic healing physiology are unclear. Also, commonly used carbon dioxide (CO2) is a known vasodilator that improves tissue oxygen tension. We performed a systematic review to determine the influence of hyperoxia, hypoxia, and hypercapnia on the gut microbiome and anastomotic healing. METHODS: A literature search was performed in MEDLINE, EMBASE, and COCHRANE to identify studies investigating the effects of hyperoxia, hypoxia, and hypercapnia on anastomotic healing and gut microbiota published between 1998 and 2018. Two reviewers screened the articles for eligibility and quality. Fifty-three articles underwent full text review, and a narrative synthesis was undertaken. RESULTS: Hyperoxia is associated with better anastomotic healing, increased gastrointestinal oxygen tension, and may reduce gut anaerobes. Hypoxia is associated with poor healing and increased gut anaerobes. However, it is unclear if hypoxia is the most important predictor of anastomotic leaks. Low pressure CO2 pneumoperitoneum and mild systemic hypercapnia are both associated with increased gastrointestinal oxygen tension and may improve anastomotic healing. We found no studies which investigated the effect of hypercapnia on gut microbiota in the context of anastomotic healing. CONCLUSIONS: Tissue oxygenation influences gut anastomotic healing, but little evidence exists to demonstrate the influence on the gut microbiome in the context of healing. Further studies are needed to determine if anastomotic microbiome changes with altered tissue oxygenation and if this affects healing and leak rates. If confirmed, altering tissue oxygenation through hyperoxia or hypercapnia could be feasible means of altering the microbiome such that anastomotic leak rates reduce.

Literature Review on the Incidence of Primary Stapler Malfunction.

Background. Surgical stapling devices are known for their reliability and convenience. A letter to health care professionals published by the US Food and Drug Administration in March 2019 highlighted the increasing number of adverse events associated with surgical staplers. Driven by a case of stapler malfunction during an elective laparoscopic sleeve gastrectomy, we performed a literature review to investigate the incidence of primary stapler malfunction. We also discuss the common types and an approach to its management. Methods. PubMed, MEDLINE, and EMBASE databases were searched for articles discussing surgical stapler malfunction. Twelve studies were selected that described the incidence and/or consequences of primary stapler malfunction. A narrative synthesis was performed. Results. From observational studies, the incidence ranged from 0.022% to 2.3%. A prospective survey reported that 86% of laparoscopic surgeons either had personal experience with or knew of surgeons who experienced stapler malfunction, implying a higher incidence. Underreporting has been an issue as manufacturers can get exemptions from public reporting. Significantly, higher malfunctions have been reported after exemptions were lifted. The most common types of stapler malfunction are stapler misfire and stapler locking. Major morbidity and mortality have been reported. Conclusion. Surgeons are increasingly reliant on technological innovations. Stapling failure occurs and it is imperative to be aware of this. Given the high volume of stapler use, a high percentage of surgeons are likely to encounter this problem in their career. It is important to have an approach to the prevention and management of this potentially catastrophic complication.