Table 2:

Recent¹ Literature Highlights in Cancer Microbiome Research

Reference	Study Type	Study Goal	Human Population Studied (N)	Major Findings
GI Cancers
Colorectal Cancer
Dejea CM et al (39)	Mouse model & human samples	To study the role of biofilm formation in the progression of hereditary colon cancer.	5 FAP patients, 1 juvenile polyposis syndrome patient	Biofilms containing co-colonization with ETBF and pks+ E. coli promotes carcinogenesis through mucus degradation enabling pks+ E. coli adherence and subsequent DNA damage as well as IL-17 induction by both bacteria.
Kitamoto S et al (35)	Mouse model	To investigate how periodontal inflammation exacerbates gut inflammation	N/A	Oral pathobionts and oral pathobiont-reactive Th17 translocate to the gut and cause development of colitis.
Pleguezlos-Manzano C et al (14)	Organoid & human samples	To identity mutagenic characteristics of pks+ E. coli	5786 cancer genomes	Revealed a distinct mutational signal in organoids injected with pks+ E. coli that was detected in a subset of predominantly CRC human cancer genomes.
Wilson MR et al (22)	Cell lines & mouse model	To determine the molecular mechanism of the genotoxic effects of colibactin	N/A	Colibactin alkylates DNA in vitro and the metabolite was identified in mice colonized with pks+ E. coli.
Pancreas
Geller LT et al (55)	Mouse model & human samples	To study impact of microbes on PDAC chemotherapy	113 human PDAC samples	Mouse model: Bacteria, likely Gammaproteobacteria, metabolize the chemotherapeutic drug gemcitabine via long isoform of cytidine deaminase conferring gemcitabine resistance; Human samples: PDACs contain Gammaproteobacteria populations.
Pushalkar S et al (56)	Mouse model & human samples	To define PDAC microbiome-mediated immune mechanisms of oncogenesis	Fecal samples (N=32 patients with PDAC; N=31 healthy volunteers); Pancreas tissue samples (N=5 healthy or PDAC patients each)	Mouse model: The PDAC microbiome promotes disease progression through innate immune & T-cell intratumoral immunosuppressive mechanisms that can enable response to checkpoint-based immunotherapy. Human samples: Proteobacteria are prominent in PDAC tissues. Comparison of patients with both gut & PDAC microbiome analysis suggest increase translocation of Proteobacteria to the pancreas.
Riquelme E et al (57)	Mouse model & human samples	To identify microbiome mechanisms contributing to long-term survival in PDAC patients.	PDAC tissues from short-term survivors (STS) (N=22 primary cohort, 10 validation cohort) & long-term survivors (LTS) (N=21 primary cohort, 15 validation cohort); stools from PDAC STS, LTS-no disease & healthy controls (N=8–17/group)	Mouse model: Human-to-mouse FMT from STS, LTS or controls differentially modulated the tumor microbiome, TME and tumor progression, mirroring patient outcomes. Human samples: STS and LTS PDAC patients display distinct tumor microbiomes with LTS PDAC enriched in Proteobacteria, Actinobacteria and Bacillus clausii.
Gastric
Choi IJ et al (47)	Human samples	To determine whether antibiotic clearance of H. pylori can prevent development of metachronous gastric cancer	Prospective clinical trial of 470 patients who had prior endoscopic resection of early gastric cancer or high-grade adenoma and received either antibiotics (to clear H. pylori) or placebo	H. pylori antibiotic clearance reduced the incidence of metachronous gastric cancer by nearly 50% (13.4% vs. 7.2% treatment vs. placebo) and improved gastric corpus atrophy.
Non-GI Cancers
Lung
Greathouse KL et al (66)	Human samples	To define the microbiome associations of lung cancer vs patient-matched normal lung tissues.	Retrospective analysis of prospective National Cancer Institute-Maryland study; N=106 matched pairs of lung tumor and non-tumor tissues. Includes a TCGA-derived validation cohort.	Identified microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissues. Specifically, enrichment of Acidovorax spp. in smoking-associated squamous cell carcinoma lung cancers with TP53 mutations.
Jin C et al (67)	Mouse model	To identify the contribution of the local lung microbiota to lung cancer development	N/A	Local lung microbiota promotes lung cancer development in KP mice. Local lung dysbiosis induces tumor-promoting inflammation attributable to ɣδ –T17 cells and myeloid cells.
Tsay J-C J et al (68)	Mouse model & human samples	To define human microbial signatures associated with lung cancer prognosis & disease mechanisms.	N=83 prospectively enrolled lung cancer patients	Human samples: A lower airway microbiota signature enriched with oral commensals associated with worse lung cancer prognosis. Human samples & mouse model: Lung cancer dysbiosis was associated with upregulation of IL-17, PI3K-AKT, MAPK and ERK pathways as well as IL-6/IL-8. Veillonella parvula was the most abundant taxon driving the association.
Breast
Parhi L et al (70)	Mouse model & human samples	To investigate the contribution of Fusobacterium nucleatum to breast cancer development.	N=50 FFPE breast cancer samples with N=30 matched adjacent non-tumor tissues	Human samples: Gal-GalNAc levels are increased in breast cancer samples. Using 16S rRNA amplicon sequencing, ~30% of breast cancer samples displayed increased F. nucleatum reads. Mouse model: IV inoculation of F. nucleatum into an orthotropic breast cancer model resulted in Fap2-mediated F. nucleatum tumor colonization and enhanced tumor growth inhibited by antibiotics.
Parida S et al (71)	Mouse model & human samples	To investigate the breast microbiome	Utilized available human datasets comparing benign & malignant breast tumors as well as nipple aspirate fluids of breast cancer survivors & healthy volunteers	Human data: Meta-analysis of breast cancer microbiome studies identified Bacteroides fragilis in breast tumor tissues. Mouse model: Gut or breast intraductal colonization with a toxin-producing molecular subset of B. fragilis (ETBF) induced growth and metastasis of breast cancer cells potentially mediated by β–catenin and Notch1 signaling.
Head & Neck
Hayes RB et al (64)	Human samples	To define whether changes in the oral microbiome precede HNSCC	Oral rinse samples from 383 patients from the CPS-II and PLCO studies, including 129 incident cases of HNSCC and 254 controls	The strongest microbial associations identified were protective effects of Kingella and Corynebacterium genera in larynx cancer and smokers, a biologically plausible mechanism due to the cigarette toxin-neutralizing capabilities of these taxa.
Genitourinary
Shrestha E et al (83)	Human samples	To define whether the urinary microbiome is associated with prostate cancer	Urine samples from 135 men with or without prostate cancer	Total prostate cancer cases did not cluster differently from controls; however, a cluster of cases harbored a striking flora containing 6 pro-inflammatory bacteria suggesting possible subsets of prostate cancer that may be driven by the urinary microbiome.

Abbreviations: CRC, colorectal cancer; ETBF, enterotoxigenic Bacteroides fragilis; FAP, familial adenomatous polyposis; Fap2, Fusobacterium adherence protein 2; FFPE, formalin-fixed paraffin-embedded; FMT, fecal microbiota transplantation; GI, gastrointestinal; KP, mice bearing Kras mutation and p53 loss; N/A, not applicable; PDAC, pancreatic ductal adenocarcinoma; TCGA, The Cancer Genome Atlas; TME, tumor immune microenvironment.

¹Recent defined as 2016 or later