This study investigated the differences in clinical changes before and after bariatric surgery in the microbiota environment in the gastric mucosa of patients with obesity, DM, and H. pylori infection. Notably, except for gastric studies on H. pylori, studies on commensal microbiota and their roles in DM and obesity are limited. Gastric bacterial communities other than H. pylori were first profiled in the early 2000s (Monstein et al., 2000). The most abundant bacteria isolated from healthy human stomachs were Veillonella, Lactobacillus, Clostridium (Zilberstein et al., 2007), Cuibacterium, Streptococcus, and Staphylococcus (Delgado et al., 2013). Some studies profiled all taxa at different taxonomic levels, whereas others focused only on microbiota capable of distinguishing certain gastric diseases from controls with significant differences in the definition of “healthy control.” Nevertheless, five major phyla—Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria—have consistently been observed in healthy populations (Andersson et al., 2008; Stearns et al., 2011; Engstrand et al., 2013; Nardone et al., 2017; Gunathilake et al., 2021). Especially at the genus level, Streptococcus, Prevotella, Veillonella, and Rothia were most frequently observed. Similar communities were detected in the present study. Helicobacter was dominant among the patients infected with H. pylori (the ND-HP and DM-HP groups), followed by Cutibacterium and Streptococcus. These results suggest that these bacteria interact with each other to survive in harsh gastrointestinal environments. We confirmed their interactions in the H. pylori-infected group through co-occurrence analysis, and their functions were predicted using PICRUSt2. The Cutibacterium genus was the most dominant, followed by Streptococcus and Staphylococcus, in the groups with obesity and DM (the ND and DM groups).
Notably, in the functional prediction analysis, pathways such as flagellar assembly, lipopolysaccharide biosynthesis, bacterial chemotaxis, and biotin metabolism were identified in the ND-HP group. Flagella are protein structures that many bacteria use for movement, and H. pylori and other bacterial species are flagellated pathogen. Flagella are important in H. pylori pathogenesis and allow the bacteria to move through the thick mucus layer of the stomach lining and reach the underlying epithelial cells, where they can establish an infection. In addition, flagella induce inflammation and immune responses that contribute to gastric disease development, such as gastritis, peptic ulcers, and gastric cancer (Gu et al., 2017).
Lipopolysaccharide (LPS) is a large molecule in the outer membrane of many gram-negative bacteria. LPS maintains the structural integrity of bacterial cells and the interaction of bacteria with their environment. Bacterial chemotaxis is the movement of bacteria toward or away from chemical cues in the environment. This process is crucial for bacterial survival and colonization in various environments. Biotin is an important vitamin for carbohydrate, fat, and amino acid metabolism by bacteria.
Co-occurrence analysis of the ND-HP and DM-HP groups showed that the CC of the microbial groups was higher than that of the ND. This finding is possibly due to the formation of stronger interactions between different microbial groups owing to the disturbance by H. pylori, which dominates the gastric environment, or the effect of their virulence factors. H. pylori causes an imbalance in the gut microbiome by altering the population of other microbiomes residing in the gut (Mohammadi et al., 2020; Saxena et al., 2020; Martin-Nuñez et al., 2021; Peng et al., 2021). In particular, H. pylori can release virulence factors impacting the intestinal epithelium, causing inflammation and further perturbation of the gut microbiome (Baj et al., 2020).
Clinical parameters improved in all groups following sleeve gastrectomy. However, individuals harboring H. pylori did not show significant differences in clinical improvement. This suggests that the efficacy of surgery may be hindered depending on the presence of H. pylori infection in obese/diabetic patients. Although the relationship between obesity and H. pylori infection remains controversial, the eradication rate of H. pylori infection is particularly low in patients with obesity compared to that in normal individuals. Two possible reasons for this have been suggested. First, physiological changes that occur in obesity, such as delayed gastric emptying, can decrease the rate of drug absorption, regardless of the drug properties (Maddox et al., 1989). Second, the distribution volume of drugs may be altered in patients with obesity because the increase in adipose tissue may affect drugs with lipophilic properties (Cheymol et al., 2000; Pai et al., 2007). However, most studies on bariatric surgery and H. pylori infection focused on the effect of H. pylori on marginal ulcers after bariatric surgery. Therefore, studies are needed on H. pylori infection, changes in gastric microbes, and clinical changes caused by obesity surgery in patients who are morbidly obese.
This study had some limitations. First, our study lacked sufficient number of clinical groups and simultaneous monitoring of changes in the stool or gastric microbiome before and after bariatric surgery. Second, owing to the absence of normal controls, the standard clinical data can only be compared with that before surgery. Moreover, experimental verification, such as metabolomic analysis, is needed to identify the causative factors that affect the clinical effects. Nonetheless, this study is the first to predict the prognosis of bariatric surgery through the state of the gastrointestinal microbes of patients who are morbidly obese and microbes in an environment dominated by Helicobacter. Therefore, these results can be used to develop clinical guidelines for obesity surgery and prescriptions to reduce obesity.
In conclusion, although sleeve gastrectomy had an improvement effect in patients with morbid obesity and diabetes, it may hinder clinical improvement of the gastric microbiota composition co-existing with H. pylori in patients who are morbidly obese with H. pylori infection. In future studies, we will collect gastrointestinal microbiome and clinical data from healthy participants with or without H. pylori infection, thereby investigating the effective and active improvement of obesity by comparing them with patients who are morbidly obese with gastric microbes following bariatric surgery.