with Dr. Romina Pena
HISTORIC BACKGROUND Intestinal antisepsis began in the 1900s with the goal of lowering morbidity and mortality rates after strangulated bowel obstruction surgery. Before the antibiotic era, scientists discovered that irrigation of the obstructed bowel prevented mortality by eliminating toxins that were related to intestinal bacteria. A study by Dr. Dragstedt from the University of Chicago published in 1916 showed that bacterial activity plus necrotic tissue, or the absorption of toxic products resulting from their interaction, was the significant factor in rapid death in simple closed intestinal loops. In the late 1900s, surgical researchers discovered that cleansing agents did not eliminate microbial burden but helped non-absorbable oral antibiotics do so, targeting mucosal bacteria. A seminal study by Dr. Cohn, published in 1956, showed that the application of intraluminal antibiotics protected an ischemic anastomosis, keeping it viable. Experiments were performed on animals to test different antiseptic regimes which were then applied to humans in the 1970s, significantly lowering postoperative complications. CURRENT DILEMMA As mortality and morbidity rates continued to decrease in the 2000s, surgeons began to question the need for MOABP, leading to multiple randomized controlled trials that showed that it did prevent surgical site infections (SSIs) and anastomotic leaks (ALs). Recent studies have shown contradictory data: In February 2019, the SELECT trial was published. It was a RCT that included 455 patients and concluded that selective digestive decontamination (SDD) with oral antibiotics (oral colistin, tobramycin and amphotericin B) reduces infectious complications after colorectal cancer resection but did not significantly reduce anastomotic leakage. In August 2019, the MOBILE trial was published, stating that MOABP does not reduce SSIs or overall morbidity when compared to NBP (no bowel preparation) for colectomy patients. It was a RCT, multicenter study, including 417 patients. SSI was detected in 7% of the patients assigned to MOABP versus 7% of those assigned to NBP. This study also addressed anastomotic leaks, reporting a 4% rate in both groups. The authors suggested that recommendations on the use of MBP for colectomies should be revisited. To this day, even though there have been numerous publications on the subject, there is no mechanistic explanation as to why intestinal antisepsis seems to work favorably for some patients and not for others. A review from Dr. Alverdy brilliantly states that the variability of practices and results in this field is due to “the lack of foundational science” behind it. There is a need to understand the basic science involved in bowel preparation and redesign it according to our patients’ needs. THE ROLE OF INTESTINAL MICROBIOME There is a rapidly growing body of evidence showing that the intestinal microbiome plays a very important role in human health and disease. Dr. Alverdy’s surgical research group from the University of Chicago have been responsible for a substantial amount of knowledge in this field. Significant efforts have been made to characterize not only the taxonomy of the microbes but also their function and interactions between themselves and the host. Bacterial virulence is known to be activated by a stressful environment (i.e. depletion of nutrients after colonic lavage) and to lead to postoperative complications. Research suggests that the pathophysiology of surgical infection is more complex than it seems. It is known than bacteria and their metabolites affect healing locally (i.e. colorectal anastomosis) and remotely (i.e. surgical wounds). In 2015, Dr. Shogan questioned whether bacteria can actually influence anastomotic healing. A year later, he successfully proved that a collagenolytic E. faecalis can contribute to anastomotic leakage. Regarding surgical wound healing, the myth of fecal contamination was brought down by Dr. Krezalek’s paper on the Trojan Horse Hypothesis for MRSA traveling from the gut to cause postoperative infections. BOWEL PREP 2.0 Even with level A evidence suggesting the importance of a healthy microbiome, the preparations used for bowel cleansing have not changed in decades, perpetuating the “broad-kill strategy”, eliminating both harmful and beneficial members of the intestinal microbiota. Furthermore, antibiotic resistance, dietary patterns and other important factors have not been taken into consideration to redesign intestinal antisepsis protocols. A very recent paper by Dr. Gaines shows the influence of diet on collagenolytic bacteria that associates with anastomotic leakage and cancer recurrence. Recent evidence begins to show clues on what “bowel prep 2.0” will look like (i.e. addition of probiotics or chemical compounds). For example, a paper by Dr. Hyoju shows that the addition of oral polyphosphate in mice that underwent a colorectal surgery procedure prevented anastomotic leak by inhibiting the collagenolytic activity of Serratia marcescens and Pseudomona aeruginosa. The goal is not to forgo bowel preparation but to redesign it to nurture the microbiome and suppress the pathobiome. Recent technologies have emerged, making it possible to screen patients for collagenolytic bacteria. With this information, a personalized bowel preparation could be possible, targeting problematic pathogens. Prehabilitation (i.e. a high-fiber diet) could also be part of a new protocol in addition to bowel prep 2.0 to prevent postoperative complications. TAKE HOME MESSAGES
Clinical Background
Microbiome science is proving to be a key factor to understand how to correctly prepare the gastrointestinal tract for surgery
Bowel preparations in the future should “selectively control” instead of “indiscriminately eliminate” the bacteria in order to preserve healthy gut function and prevent postoperative complications
Bowel prep 2.0 may include dietary prehabilitation and personalized antibiotics after pathogen screening
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