Altered Gastric Microbiota and Inflammatory Cytokine Responses in Patients with Helicobacter pylori-Negative Gastric Cancer

Abstract

The role of the gastric mucosal microbiome in Helicobacter pylori-negative gastric cancer (GC) remains unclear. Therefore, we aimed to characterize the microbial alterations and host inflammatory cytokine responses in H. pylori-negative GC. Gastric mucosal samples were obtained from 137 H. pylori-negative patients with GC (n = 45) and controls (chronic gastritis or intestinal metaplasia, n = 92). We performed 16S rRNA gene sequencing (n = 67), a quantitative reverse transcription-polymerase chain reaction to determine the relative mRNA expression levels of TNF (tumor necrosis factor), IL1B (interleukin 1 beta), IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), IL10 (interleukin 10), IL17A (interleukin 17A), TGFB1 (transforming growth factor beta 1) (n = 113), and the correlation analysis between sequencing and expression data (n = 47). Gastric mucosal microbiota in patients with GC showed reduced diversity and a significantly different composition compared to that of the controls. Lacticaseibacillus was significantly enriched, while Haemophilus and Campylobacter were depleted in the cancer group compared to the control group. These taxa could distinguish the two groups in a random forest algorithm. Moreover, the combined relative abundance of these taxa, a GC microbiome index, significantly correlated with gastric mucosal IL1B expression, which was elevated in the cancer group. Overall, altered gastric mucosal microbiota was found to be associated with increased mucosal IL1B expression in H. pylori-negative GC.

Identification of aging-related genes in Helicobacter pylori infection

“…Moreover, IL1B, IL6, and CXCL8 have been proven to regulate the association between chronic HP infection and the process of GC. A previous study reported that CXCL2 was a common gene between HP infection and spontaneous intracerebral hemorrhage [24][25][26][27][28]. In our study, CXCL1, CXCL2, and CXCL8 were upregulated in the group with HP infection.…”

Gut microbiome alterations during gastric cancer: evidence assessment of case–control studies

“…Fourteen studies reported on people infected with Helicobacter pylori . A total of 25 studies collected samples from gastric mucosal biopsies during gastroscopy, while four studies used fecal samples ( Liang et al, 2019 ; Qi et al, 2019 ; He et al, 2022 ; Kim et al, 2022 ), and four studies used gastric juice samples ( Park et al, 2022 ; Sun et al, 2022 ; Peng et al, 2023 ; Wei et al, 2023 ). Twenty-seven studies used 16S gene sequencing technology, but with different amplified regions.…”

Investigating the impact of gut microbiota on gastric cancer through the involvement of immune cells: a comprehensive Mendelian randomization study and mediation analysis

“…Previous research has indicated a decrease in Haemophilus in the oral microbiome of individuals with GC, as well as a reduction in the presence of Haemophilus parain uenzae in GC [30]. Nevertheless, a different study indicated a rise in the prevalence of Haemophilus in GC [31], potentially linked to their connection with functional dyspepsia in the control group rather than intestinal metaplasia in the control group [29]. These results indicate that the Haemophilus has different effects on GC at different stages, and our study showed that the Haemophilus has a certain promoting effect on GC.…”

“…Due to its ability to reduce nitrates, the presence of Haemophilus may play a role in the ongoing in ammation process [28]. And it has also been shown that a negative relationship between the levels of Haemophilus and IL-1B mRNA [29]. Previous research has indicated a decrease in Haemophilus in the oral microbiome of individuals with GC, as well as a reduction in the presence of Haemophilus parain uenzae in GC [30].…”