Table 2.

Studies investigating PDAC intratumoral microbiota. Number of subjects (N); pancreatic ductal adenocarcinoma (PDAC); healthy control (HC); chronic pancreatitis (CP); pancreatic neuroendocrine tumor (NET); pancreatic cyst (PCy); intraductal papillary mucinous neoplasm (IPMN); long-term PDAC survivor (LTS); short-term PDAC survivor (STS).

Ref.	Study Design	N. PDAC Patients	N. Controls	Detection Method	Microbiota Association	Main Findings/Authors’ Conclusion
Nilsson et al., 2006 [63]	Case-control study	40	7 HC 5 CP 14 NET 10 other	Surgical specimen, DNA genus-specific PCR	Helicobacter DNA detected in the pancreas of 75% of patients with adenocarcinoma but not detected in any control	Helicobacter DNA, mostly H. pylori genus, commonly detected in pancreatic cancer.
Rogers et al., 2017 [64]	Cross-sectional study	50	/	Pancreatic fluid, bile or jejunal contents, 16S rRNA V4 amplicon sequencing	An enrichment of Klebsiella spp. and a decrease in Faecalibacterium prausnitzii and Roseburia spp. in fecal samples of PDAC patients	Klebsiella pneumoniae and Klebsiella oxytosa prepondernace in PDAC. Death at 1 year was associated with decreased Klebsiella within fecal samples of PDAC patients.
Mitsuhashi et al., 2015 [50]	Cross-sectional study	283	/	Surgical specimen PCR	Fusobacterium increased in PDAC	Significantly shorter survival observed in the Fusobacterium species-positive group.
Geller et al., 2017 [65]	Cross-sectional study	65	20	Surgical specimen 16S rRNA V6 amplicon sequencing	Increased Proteobacteria in PDAC	Increased presence of Gammaproteobacteria in PDAC tissue contributes to gemcitabine resistance.
Gaiser et al. 2018 [49]	Case-control study	27	57 IPMN PCy 21 non-IPMN PCy	Cyst fluid and plasma samples 16S rRNA qPCR and full-length gene sequencing	Firmicutes and/or Proteobacteria increased in PDAC	Higher overall microbial diversity in PDAC.
Del Castillo et al., 2019 [66]	Cross-sectional study	31	18 CPPCy 8 other	16S rRNA V3-V4 amplicon sequencing	Porphyromonas, Capnocytophaga, Prevotella, Selenomonas and Fusobacterium spp. higher abundance in PDAC patients	The authors observed that pancreatic and gut microbiota are highly subject-specific and differ between PDAC and noncancer subjects.
Riquelme et al., 2019 [67]	Case-control study	37 LTS	31 STS	Tumor cores 16S rRNA V4 amplicon sequencing	Pseudoxanthomonas- Streptomyces- Saccharopolyspora-Bacillus clausii highly predictive of long-term survivorship	Fecal microbiome transfer from LTS patients reduced tumor growth in mice compared to STS patients.
Nejman et al., 2020 [68]	Retrospective study	67	/	Tumor cores 16S rRNA V6 amplicon sequencing	Fusobacterium nucleatum enrichment in PDAC	The human tumor microbiome is composed of tumor type-specific intracellular bacteria present in both cancer and immune cells.
Aykut et al., 2019 [69]	Case-control study	13	18 fecal samples	18S ITS1 amplicon sequencing	Parastagonospora, Saccharomyces, Septoriella and Malassezia genera enriched in PDAC patients	Human PDAC samples markedly enriched for Malassezia spp.