The Role of Microbiota in Pancreatic Cancer

Papa, Valerio; Schepis, Tommaso; Coppola, Gaetano; Chiappetta, Michele Francesco; Vecchio, Livio Enrico Del; Rozera, Tommaso; Quero, Giuseppe; Gasbarrini, Antonio; Alfieri, Sergio; Papa, Alfredo

doi:10.3390/cancers15123143

Cited by 13 publications

(4 citation statements)

References 128 publications

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“…The subject of many studies is that the reduction in metabolites indicates a change in the microbial load in patients with pancreatic cancer. The composition of the microbiota can be influenced not only by pathogenetic changes [19], but also by treatment, including chemotherapy and antibiotic therapy before or after surgery. Changes in the metabolomic profile are considered in connection with preoperative factors, such as "antibiotic therapy" and "chemotherapy", which may indirectly reflect the severity of the condition and the possibility of developing infectious complications.…”

Section: Discussionmentioning

confidence: 99%

Blood Serum and Drainage Microbial and Mitochondrial Metabolites in Patients after Surgery for Pancreatic Cancer

Getsina,

Tsyba,

Polyakov

et al. 2023

Metabolites

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Pancreatic cancer (PC) has the highest mortality rate of all major cancers in the world despite improvements in clinical care and an understanding of the biology of pancreatic cancer. A study of 64 patients with verified pancreatic cancer who underwent surgery was included. Sampling was carried out at three points: before surgery and on days 1–3 after surgery and 5–7 days after surgery. Drainage fluid collection was taken from the drains installed intraoperatively one day after surgery. Tyrosine and phenylalanine metabolites and two mitochondrial metabolites, namely succinic and fumaric acids, were identified and quantified by GC-MS in the serum of healthy donors and patients. Differences in the metabolomic profile were found between the patients and healthy people. A statistically significant decrease in the level of p-hydroxyphenyllactic acid (p-HPhLA), the amount of sum 3 sepsis-associated metabolites (Σ 3AMM), as well as fumaric and succinic acids in patients was observed. It was also noted that p-hydroxyphenyllactic acid in the preoperative period may be considered as a predictor of complications and longer postoperative recovery.

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Section: Discussionmentioning

confidence: 99%

Blood Serum and Drainage Microbial and Mitochondrial Metabolites in Patients after Surgery for Pancreatic Cancer

Getsina,

Tsyba,

Polyakov

et al. 2023

Metabolites

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show abstract

“…Moreover, HSCs produce factors such as VEGF and angiopoietin 1, which facilitate the capillarization process of LSECs. Products such as lipopolysaccharides (LPSs) and others derived from gut bacteria are also involved in the onset of systemic hyperdynamic circulation and the dysfunction of extraintestinal organs [51,52]. Figure 1 summarizes the main mechanisms of portal hypertension.…”

Section: Ph In Liver Cirrhosis and Hcc: Physiopathologymentioning

confidence: 99%

Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives

De Gaetano,

Pallozzi,

Cerrito

et al. 2024

Cancers

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The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as “hepatocellular carcinoma”, “immune checkpoint inhibitors”, “systemic therapy”, “portal hypertension”, “variceal bleeding” and “tyrosine kinase inhibitors”. Despite promising results of tyrosine kinase inhibitors in animal models for PH and fibrosis, only Sorafenib has demonstrated similar effects in human studies, whereas Lenvatinib appears to promote PH development. The impact of Atezolizumab/Bevacizumab on PH remains uncertain, with an increasing risk of bleeding related to Bevacizumab in patients with prior variceal hemorrhage. Given the absence of specific guidelines, endoscopic surveillance during treatment is advisable, and primary and secondary prophylaxis of variceal bleeding should adhere to the Baveno VII recommendations. Furthermore, in patients with advanced HCC, refinement of diagnostic criteria for CSPH and guidelines for its surveillance are warranted.

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“…6 A disrupted gut microbiota (GM) can lead to chronic inflammation, which plays a role in the pathogenesis of PC. 7 Mendelian randomization (MR) is a method using genetic variants associated with a risk factor as an exposure to assess whether there is a causal effect on outcomes, minimizing the impact of external confounders. 8,9 Moreover, these genetic variants can potentially regulate DNA methylation (DNAm), gene expression, protein levels and the abundance of GM.…”

Section: Backg Rou N Dmentioning

confidence: 99%

Causal effect of gut microbiota on pancreatic cancer: A Mendelian randomization and colocalization study

Li,

Liang

2024

J Cellular Molecular Medi

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The causal relationship between gut microbiota (GM) and pancreatic cancer (PC) remains unclear. This study aimed to investigate the potential genes underlying this mechanism. GM Genome‐wide association study (GWAS) summary data were from the MiBioGen consortium. PC GWAS data were from the National Human Genome Research Institute‐European Bioinformatics Institute (NHGRI‐EBI) GWAS Catalogue. To detect the causal relationship between GM and PC, we implemented three complementary Mendelian randomization (MR) methods: Inverse Variance Weighting (IVW), MR‐Egger and Weighted Median, followed by sensitivity analyses. Furthermore, we integrated GM GWAS data with blood cis‐expression quantitative trait loci (eQTLs) and blood cis‐DNA methylation QTL (mQTLs) using Summary data‐based Mendelian Randomization (SMR) methods. This integration aimed to prioritize potential GM‐affecting genes through SMR analysis of two molecular traits. PC cis‐eQTLs and cis‐mQTLs were summarized from The Cancer Genome Atlas (TCGA) data. Through colocalization analysis of GM cis‐QTLs and PC cis‐QTLs data, we identified common genes that influence both GM and PC. Our study found a causal association between GM and PC, including four protective and five risk‐associated GM [Inverse Variance Weighted (IVW), p < 0.05]. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found. The gene SVBP was identified as a GM‐affecting gene using SMR analysis of two molecular traits (FDR<0.05, P_HEIDI>0.05). Additionally, two genes, MCM6 and RPS26, were implicated in the interaction between GM and PC based on colocalization analysis (PPH4>0.5). In summary, this study provides evidence for future research aimed at developing suitable therapeutic interventions and disease prevention.

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The Role of Microbiota in Pancreatic Cancer

Cited by 13 publications

References 128 publications

Blood Serum and Drainage Microbial and Mitochondrial Metabolites in Patients after Surgery for Pancreatic Cancer

Blood Serum and Drainage Microbial and Mitochondrial Metabolites in Patients after Surgery for Pancreatic Cancer

Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives

Causal effect of gut microbiota on pancreatic cancer: A Mendelian randomization and colocalization study

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