Impact of gut microbiome in the development and treatment of pancreatic cancer: Newer insights

Table 1 Gut microbiota associated with Pancreatic oncogenesis

Bacteria	Primary site	Potential mechanism	Subsequent effect	Ref.
Porphyromonas gingivalis	Mouth	TLR signaling disruption; Nitrosamines production; PPAD production	Loss of protective immunity; DNA adducts formation; P53 overactivity (loss of apoptosis); KRAS mutation (cellular overproliferation)	[52-55]
Aggregatibacter actinomycetemcomitans	Mouth	Nitrosamine production; DNA double-strand breaks; CagE production	DNA adducts formation; genome instabilities; dysregulation of DNA methylation expression	[52,58,59]
Fusobacterium nucleatum	Mouth	FadA production; Fap2 production	activation of the Wnt/β-catenin pathway; suppression of the cytotoxic effects of NK cells and lymphocytes	[59,61-63]
Helicobacter Pylori	Stomach	cagA, cag PAI and vacA production	Disruption of host intracellular signaling pathways	[64]
Bacteroides fragilis, Bacteroides vulgatus, Listeria monocytogenes, Clostridium, Lactobacillus, Bifidobacterium	Large bowel	Transformation of primary bile acids to secondary bile acids	Reduction of susceptibility to apoptosis, induction of inflammatory mediators, and perturbation of membranes and cellular movement	[76]
Escherichia coli	Large bowel	Polyamines production	Polyamines upregulation	[81-83]

TLR: Toll-like receptor; PPAD: Porphyromonas Peptidyl Arginine Deaminase; CagE: Cytotoxin-associated gene E; NK: Natural killer; PAI: Pathogenicity island; cagA: Cytotoxin-associated gene A.

Table 2 Impact of gut microbiota in the treatment of Pancreatic cancer

Bacteria	Primary site	Potential mechanism	Subsequent effect	Ref.
Escherichia coli	Large bowel	Cytolysin A production; Cytolethal distending toxin production	Imposing cell death in the eukaryotic membrane by the caspase-dependent pathway; DNA double stranded breaks, leading to cell cycle arrest and cytotoxicity	[49,86,87]
Staphylococcus aureus	Variable	Cytolysin A production	Imposing cell death in the eukaryotic membrane by the caspase-dependent pathway	[86]
Streptococcus pyogenes	Variable	Streptolysin O production	Increase in apoptosis and cytolysis	[88]
Aggregatibacter actinomycetemcomitans, Campylobacter and Helicobacter	Mouth, stomach, large bowel	Cytolethal distending toxin production	DNA double stranded breaks, leading to cell cycle arrest and cytotoxicity	[87]
Lactobacillus casei	Mouth and small intestine	P53 activation	Upregulation of apoptosis	[90]
Bacteroidales, Burkholderiales	Large bowel	CTLA-4 upregulation	Enhancing activity of monoclonal antibody against CTLA-4	[95]

CTLA-4: Cytotoxic T-lymphocyte-associated protein 4.