Distal Gastrectomy with Billroth II Reconstruction is Associated with Oralization of Gut Microbiome and Intestinal Inflammation: A Proof-of-Concept Study

Abstract

Background Subtotal gastrectomy with Billroth II reconstruction (SGB2) results in increased gastric pH and diminished gastric barrier. Increased gastric pH following PPI therapy has an impact on the gut microbiome, intestinal inflammation, and possibly patient health. If similar changes are present after SGB2, these can be relevant for patient health and long-term outcomes after surgery. The aim of the study is to investigate whether SGB2 is associated with specific changes in gut microbiome composition and intestinal inflammation. Patients and Methods This cross-sectional proof-of-concept study includes patients after SGB2 ( n = 14) for early gastric cancer and their nongastrectomized in-house relatives as controls ( n = 8). Fecal microbiome composition, intestinal inflammation (fecal calprotectin), gut permeability (DAO, LBP, sCD14), systemic inflammation (CRP) markers, and gastrointestinal symptoms are investigated. This study is registered at ClinicalTrials.gov (NCT03418428). Results Microbiome oralization following SGB2 was defined by an increase in Escherichia – Shigella , Enterococcus , Streptococcus , and other typical oral cavity bacteria ( Veillonella , Oribacterium , and Mogibacterium ) abundance. The fecal calprotectin was increased in the SGB2 group [100.9 (52.1; 292) vs. 25.8 (17; 66.5); p = 0.014], and calprotectin levels positively correlated with the abundance of Streptococcus ( r s = 0.639; p adj = 0.023). Gastrointestinal symptoms in SGB2 patients were associated with distinct taxonomic changes of the gut microbiome. Conclusions SGB2 is associated with oralization of the gut microbiome; intestinal inflammation and microbiome changes were associated with gastrointestinal symptoms. These novel findings may open gut microbiome as a new target for therapy to improve quality of life and general patient health in long-term survivors after SGB2.

Gastric Cancer Microbiome

“…Alterations on fecal microbiota, especially the dominant phyla of Bacteroidetes , Firmicutes , and Proteobacteria , may be involved in H. pylori -related gastric lesion progression [57]. Others showed that a change to oral-like microbiome occurs after distal gastrectomy, with an increase in Escherichia-Shigella, Enterococcus, Streptococcus , and other typical oral cavity bacteria ( Veillonella, Oribacterium, and Mogibacterium ) abundance [58]. Changes in the composition of the intestinal microbiome that occur after bariatric surgery can have long-term metabolic consequences that need to be elucidated [59, 60].…”

Gastrectomy impact on the gut microbiome in patients with gastric cancer: A comprehensive review

“…Following a comprehensive review of the current literature, we identified 4 studies which investigated the gut microbiome after total or subtotal gastrectomy for GC, and these are summarized in Table 1 . Three of these four studies were cross-sectional and investigated gut microbiome composition in GC patients at a median time of 3.75 years[ 27 ], 5 years[ 6 ], and 8.25 years[ 28 ] after gastrectomy and compared it with the corresponding controls. One small-scale study was longitudinal and investigated the gut microbiome composition before and approximately one week after gastrectomy[ 29 ].…”

“…Furthermore, the role of the microbiome in postoperative weight loss and other outcomes are documented after sleeve gastrectomy and Roux-en-Y gastric bypass in bariatric patients[ 21 - 26 ]. Several recent studies investigated the gut microbiome after gastrectomy for GC[ 6 , 27 - 29 ]. This comprehensive review provides an overview of the current evidence on gut microbiome after gastrectomy for GC and its clinical implication.…”

ASO Author Reflections: Gut Microbiome Oralization and Intestinal Inflammation After Distal Gastrectomy with Billroth II Reconstruction is Linked to Gastrointestinal Symptoms

“…The most commonly documented gastrointestinal symptoms in gastrectomized patients were abdominal discomfort, diarrhea, and bloating, which were associated with distinct taxonomic changes of the gut microbiome. 5 …”