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

Table 1 Clinical studies investigating gut microbiome composition in patients after gastrectomy for gastric cancer

Ref.	Type of study	Participants (groups)	Exclusion criteria	Type of gastrectomy and method of reconstruction	Main findings of the study	Other metabolites investigated
Erawijantari et al[6], 2020	CSS	Gastrectomy group: Patients with a history of gastrectomy for GC (n = 50). Control group: Healthy controls without a history of gastrointestinal surgery (n = 56)	Recurrence of gastric cancer (gastrectomy group). History of gastrointestinal surgery (for controls)	Total (n = 12) gastrectomy and subtotal gastrectomy (n = 38). Types of reconstruction: Stomach-stomach (n = 1); Billroth I (n = 2); Jejunal interposition (n = 6); Pylorus-preserving gastrectomy (n = 8); Roux-en-Y (n = 29)	Higher species diversity and richness in gastrectomized patients. Higher abundance of aerobes, facultative anaerobes, and oral microbes in gastrectomized patients	Phosphate and amino acid transporters were more abundant in gastrectomized patients. Primary and conjugated forms of bile acid enriched in the control group and deoxycholic acid more abundant in gastrectomized patients
Liang et al[29], 2019	LS	Gastrectomy group: Patients with a diagnosed GC one week before (n = 20) and ≥ 7 d after (n = 6) gastrectomy. Control group: Healthy controls (n = 22)	History of antibiotics, PPI or H2 receptor antagonist use 1 mo prior to inclusion. Endoscopic finding of peptic ulcer, tumor rupture, pyloric obstruction. Patients with a history of radiotherapy/chemotherapy and/or previous surgery	Distal gastrectomy (n = 6). Types of reconstruction: Billroth II (n = 1); Roux-en-Y (n = 5)	Increased abundance of Bacteroidetes, Fusobacteria, and Verrucomicrobia and decreased abundance of Proteobacteria, Firmicutes, and Actinobacteria after distal gastrectomy. The richness and diversity by Chao1; ACE; Shannon; and Simpson indices were similar before and after distal gastrectomy. LEfSe analysis attributed Verrucomicrobiae (genus Akkermansia) and genus Escherichia/Shigella, Lactobacillus, and Dialister to patients after gastrectomy, and the genus Klebsiella to patients before gastrectomy	Significantly decreased level of valeric acid after distal gastrectomy
Horvath et al[27], 2021	CSS	Gastrectomy group: Patients with a history of distal gastrectomy with Billroth II reconstruction for early gastric cancer (n = 14). Control group: Patient’s in-house relatives without a history of gastric surgery (n = 8)	Chemotherapy or radiotherapy 12 mo before inclusion. Gastric stump cancer. Usage of antibiotics, pro-, pre-, or synbiotics, H2-blocker, or PPI 1 month before inclusion. History of any gastrointestinal tract resections other than SGB2. Recurrence of gastric cancer, and current nongastric malignancies	Distal gastrectomy (n = 14). Types of reconstruction: Billroth II (n = 14)	Alpha diversity assessed by Shannon index was significantly decreased in gastrectomy patients. Median bacterial richness quantified by Chao1 index was similar. Beta diversity analysis showed significant differences between the microbiome composition of patients and controls; ANCOM identified the genus Escherichia-Shigella to be more abundant in gastrectomized patients. LEfSe attributed 11 additional genera to the gastrectomy group and 17 genera to the control (approximately half of them already have been implicated in PPI-induced or PPI-associated dysbiosis in previous reports). Increased abundance of Escherichia-Shigella, Enterococcus, Streptococcus, and other typical oral cavity bacteria (Veillonella, Oribacterium, and Mogibacterium) in gastrectomized patients	Fecal calprotectin marker was higher in gastrectomized patients. Fecal calprotectin was positively correlated with the abundance of Streptococcus and negatively correlated with the abundance of Ruminococcaceae, Barnesiella, Ruminococcus 2, Ruminococcus 1, and Anaerostipes. Abdominal discomfort was associated with a significantly higher abundance of Holdemanella and lower abundance of Agathobacter; Diarrhea was associated with a significantly higher abundance of Mogibacterium and significantly lower abundance of Ruminococcus 1; Bloating was associated with a significantly higher abundance of Agathobacter and Streptococcus. Patients who suffered from diarrhea also showed significantly higher serum levels of CRP and a trend to higher calprotectin level in stool compared with patients without diarrhea
Lin et al[28], 2018	CSS	Gastrectomy group: Patients with a history of distal gastrectomy for early GC (n = 111). Control group: Age and sex-matched subjects without a history of GI tract surgery (n = 344)	Age < 20 yr. Other underlying malignancies. Pre- and postoperative chemotherapy or chemoradiotherapy for GC. Other endocrine disorders such as DM, thyroid, pituitary, or adrenal disease. Moderate to severe cardiovascular, pulmonary, hepatic, or renal disease. Recurrent or uncured GC even after curative gastric surgery. The occurrence of complications after GC resection including anastomotic leakage, bleeding, intermittent intestinal adhesion, dumping syndrome, etc. Patients who received proton pump inhibitors, histamine-2 receptor antagonists, nonsteroidal anti-inflammatory drugs, antibiotics, or probiotics within one month of sample collection	Distal gastrectomy (n = 111). Types of reconstruction: Billroth II (n = 37); Roux-en-Y (n = 74)	Significantly increased richness of gut microbiome after RYGJ by Chao1 index. Tendency of increased richness of gut microbiome after SGB2 by Chao1 index. Diversity assessed by Shannon index was similar in BII patients but higher in RYGJ patients. LEfSe attributed 24 known genera, which were differently abundant between SGB2 and controls, and 43 genera differently abundant between RYJG and controls. Oscillospira, Prevotella, Coprococcus, Veillonella, Clostridium, Desulfovibrio, Anaerosinus, Slackia, Oxalobacter, Victivallis, Butyrivibrio, Sporobacter, and Campylobacter were more abundant after subtotal gastrectomy irrespective of the type of reconstruction. Increased number of aero-tolerant Streptococcus and Escherichia in the RYGJ group and Klebsiella in the SGB2 group. Increased abundance of typical oral microbiota (such as Streptococcus spp. and Veillonella spp.) in the gut microbiome of gastrectomized patients	GC patients after subtotal gastrectomy with RYGJ had a lower occurrence of metabolic syndrome and type II diabetes

CSS: Cross-sectional study; LS: Longitudinal study; GC: Gastric cancer; PPI: Proton pump inhibitors; SGB2: Subtotal gastrectomy with Billroth II reconstruction; CRP: C-reactive protein; RYGJ: Subtotal gastrectomy with Roux-en-Y reconstruction.