Effects of PD-1/PD-L1 signaling pathway on intestinal flora in patients with colorectal cancer

Colorectal cancer (CRC) ranks third in terms of global incidence and second in terms of death toll among malignant tumors. Gut microbiota are involved in the formation, development, and responses to different treatments of CRC. Under normal physiological conditions, intestinal microorganisms protect the intestinal mucosa, resist pathogen invasion, and regulate the proliferation of intestinal mucosal cells via a barrier effect and inhibition of DNA damage. The composition of gut microbiota and the influences of diet, drugs, and gender on the composition of the intestinal flora are important factors in the early detection of CRC and prediction of the results of CRC treatment. Regulation of gut microbiota is one of the most promising new strategies for CRC treatment, and it is essential to clarify the effect of gut microbiota on CRC and its possible mechanisms to facilitate the prevention and treatment of CRC. This review discusses the role of gut microbiota in the pathogenesis of CRC, the potential of gut microbiota as biomarkers for CRC, and therapeutic approaches to CRC based on the regulation of gut microbiota. It might provide new ideas for the use of gut microbiota in the prevention and treatment of CRC in the near future and thus reduce the incidence of CRC.

Section: Pectinmentioning

confidence: 71%

Therapeutic approaches to colorectal cancer via strategies based on modulation of gut microbiota

Chen

Lin

et al. 2022

“…Additionally, Pi et al (2020) identified a notable presence of Parasutterella in colorectal cancer patients undergoing PD-1 treatment. Consequently, they propose that the PD-1/PD-L1 signaling pathway may modulate the metabolic activity of intestinal flora, including Parasutterella , thus enhancing immune surveillance against tumors ( Pi et al, 2020 ). In a prior study conducted by Su et al (2023) it was similarly observed that Verrucomicrobia maintained a robust negative correlation with ICC.…”

Section: Discussionmentioning

confidence: 99%

“…An elevated prevalence of Paraprevotella, negatively correlated with hepatocellular carcinoma, may be attributed to potential mechanisms such as its anti-inflammatory properties and the inhibition of pro-carcinogenic microorganisms (Chen et al, 2015;Routy et al, 2018). Additionally, Pi et al (2020) identified a notable presence of Parasutterella in colorectal cancer patients undergoing PD-1 treatment. Consequently, they propose that the PD-1/PD-L1 signaling pathway may modulate the metabolic activity of intestinal flora, including Parasutterella, thus enhancing immune surveillance against tumors (Pi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis

Chen,

Shi,

Chen

et al. 2023

BackgroundIntrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies.Materials and methodsWe performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms.ResultsGenetically predicted increases in Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes were suggestively associated with higher ICC risk, while increases in Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment.ConclusionOur findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk.

“…Specifically, Parasutterella was found to be more abundant among responders in our study. Pi et al reported an elevated abundance of Parasutterella in patients with CRC after anti-PD-1 treatment (Pi et al, 2020 ). Additionally, Messaoudene et al observed that camu-camu reversed the anti-PD-1 resistance through direct interactions with commensal bacteria.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer

Chen

Zhang

et al. 2023

BackgroundThe association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown.MethodsFecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presented durable clinical benefits, and non-responders, if not. The composition of gut microbes was analyzed using 16S ribosomal DNA sequencing. Serum SCFA concentrations were detected using gas chromatography. Cell proliferation, migration, invasion, cell cycle, and apoptosis assays were performed on isobutyric acid-treated A549 cells. Reverse transcription-quantitative PCR, Western blotting, immunocytochemistry, and immunofluorescence staining experiments have been performed to investigate the expression of associated genes or proteins.ResultsNon-responders harbored higher microbiome α-diversity but lower β-diversity compared with responders. Compared to the patients with low α-diversity, those with high α-diversity showed significantly shorter progression-free survival. Additionally, β-diversity has also been observed between these two groups. Specifically, Parasutterella, Clostridiaceae, and Prevotella_7 were more abundant among responders, whereas Bacteroides_stercoris and Christensenellaceae_R-7_group were more abundant in non-responders. The serum SCFA (especially acetate and isobutyrate) levels tended to be higher in responders. Isobutyric acid inhibited the proliferation, migration, and invasion of A549 cells by inducing apoptosis and G1/S arrest while upregulating the expression of GPR41, GPR43, and GPR5C and downregulating that of PAR1, and increasing the activity of histone acetyltransferases.ConclusionWe revealed the influence of gut microbiota and SCFAs on the therapeutic responses in patients with LC and the anti-tumor effect of isobutyric acid, indicating their potential use as therapeutic targets.