Fusobacterium nucleatum: Unraveling its potential role in gastric carcinogenesis

Table 1 Summary of the studies with focus on Fusobacteria and Fusobacterium nucleatum in stomach and gastric cancer

Ref.	Year	Taxonomic rank	Methods	Sample type	Sample origin	No. of subjects	No. of controls	No. of preneoplastic conditions	No. of GC	GC	Major findings	Clinical value	Enriched in GC tissue
Bik et al[9]	2006	Fusobacteria	16S rRNA seq	Gastric biopsy	United States	23	11 H. pylori-negative, 12 H. pylori- positive			No	Frequent phyla: Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria
Dicksved et al[63]	2009	Fusobacteria	16S rRNA seq	Gastric biopsy	Sweden	15	5 controls		10 GC	Yes	GC microbiota not significantly different from controls, with the phyla Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria
Maldonado-Contreras et al[54]	2011	Fusobacteria	16S rRNA gene microarray	Gastric biopsy	Venezuela	12	12 healthy			No	Inverse correlation of Fusobacteria with Helicobacter
Aviles-Jimenez et al[59]	2014	Fusobacteria	16S rRNA gene microarray	Gastric biopsy	Mexico	15	5 gastritis	5 IM	5 GC	Yes	Fusobacteria among the most prevalent phyla
Parsons et al[66]	2017	Fusobacterium	16S rRNA seq	Gastric biopsy	UK	95	20 healthy, 19 PPI treated, 22 gastritis	34 AG		No	Fusobacterium lower in PPI treated patients
Yamamura et al[19]	2017	F. nucleatum	qPCR	Gastric tissue in paraffin	Japan	40	20 controls		20 GC	Yes	F. nucleatum detected in GC
Klymiuk et al[55]	2017	Fusobacterium	16S rRNA seq	Gastric biopsy	Austria	30	30 gastritis			No	Inverse correlation of Fusobacterium with H. pylori
Castaño-Rodríguez et al[22]	2017	Fusobacterium	16S rRNA seq	Gastric biopsy	Malaysia, Singapore	32	20 functional dyspepsia		12 GC	Yes	Fusobacterium enriched in GC		↑
Li et al[58]	2017	Fusobacterium	16S rRNA seq	Gastric biopsy	Hong Kong (China)	33	8 healthy, 9 gastritis	9 IM	7 GC	Yes	Fusobacterium is enriched after H. pylori eradication		↑
Coker et al[62]	2018	Fusobacterium	16S rRNA seq	Gastric biopsy	China	207	77 gastritis	74 AG; 17 IM	39 GC	Yes	Fusobacterium enriched in GC		↑
Schulz et al[53]	2018	Fusobacterium	16S rRNA seq	Saliva, gastric juice, duodenal juice, gastric biopsy, duodenal biopsy	Germany	24	8 H. pylori- positive, 16 H. pylori-negative			No	Inverse correlation of Fusobacterium with H. pylori
Hsieh et al[23]	2018	F. nucleatum	16S rRNA seq	Gastric biopsy	Taiwan	27	9 gastritis	7 IM	11 GC	Yes	Fusobacterium enriched in GC		↑
Ferreira et al[61]	2018	Fusobacteria	16S rRNA seq	Gastric biopsy	Portugal	135	81 gastritis		54 GC	Yes	Fusobacteria lower in GC; correlation with of Helicobacter		↓
Chen et al[69]	2019	Fusobacterium	16S rRNA seq	Gastric tissue	China	62			62 GC + Adj	Yes	Fusobacterium enriched in GC		↑
Shao et al[70]	2019	Fusobacteria	16S rRNA seq	Gastric tissue	China	103			36 GC + Adj	Yes	Fusobacteria enriched in GC		↑
Gantuya et al[64]	2019	Fusobacterium	16S rRNA seq	Gastric biopsy	Mongolia	75	24 controls; 11 H. pylori- positive, 40 H. pylori-negative			No	Inverse correlation of Fusobacteria with H. pylori
Guo et al[65]	2020	Fusobacterium	16S rRNA seq	Gastric biopsy	China	164	49 healthy; 115 H. pylori gastritis			No	Inverse correlation of Fusobacterium with H. pylori only in advanced gastric lesion patients
Rodriguez et al[91]	2020	F. nucleatum	Exome sequencing	Gastric tissue	United States	85			85 GC	Yes	F. nucleatum detected in GC
Gantuya et al[74]	2020	Fusobacterium	16S rRNA seq	Gastric biopsy	Mongolia	168	20 gastritis	40 IM, 40 AG	48 GC	Yes	Fusobacterium enriched in GC regardless of H. pylori infection		↑
Boehm et al[84]	2020	F. nucleatum	qPCR	Gastric tissue	Lithuania Germany	125	18 controls; 17 gastritis	9 AG/IM	81 GC + Adj	Yes	F. nucleatum-positivity associated with prognosis; lower than in CRC; no difference in AG/IM	Prognosis
Ravegnini et al[78]	2020	Fusobacteria	16S rRNA seq	Gastric tissue in paraffin	Italy	20			20 GC	Yes	signet-ring cell GCs were significantly enriched in the phyla Fusobacteria
Zhang et al[72]	2021	Fusobacteria	16S rRNA seq	Stool samples	China	146	61 healthy		85 GC	Yes	Fusobacteria enriched in GC; Fusobacteria reduced following chemotherapy		↑
Hsieh et al[86]	2021	F. nucleatum	Nested PCR	Gastric tissues	Taiwan	60			60 GC	Yes	F. nucleatum+ and H. pylori+ associated with worse prognosis	Prognosis
Nascimento et al[82]	2021	F. nucleatum	qPCR	Gastric biopsies in paraffin	Brazil	120	40 controls		80 GC	Yes	No difference to controls; F. nucleatum associated with aging
Xu et al[80]	2021	Fusobacterium	16S rRNA seq	Tongues coating	China	293	112 controls		181 GC	Yes	Fusobacterium shows diagnostic value	Diagnosis	↑
Nie et al[88]	2021	Fusobacterium	16S rRNA seq	Gastric tissue	China	61			61 GC	Yes	Fusobacteria enriched in GC and common in elderly. Fusobacterium positive GC patients more likely to have tumour-infiltrating lymphocytes
Gunathilake et al[47]	2021	F. nucleatum	16S rRNA seq	Gastric biopsy	South Korea	556	288 controls		268 GC	Yes	Fusobacteria enriched in controls		↓
Conti et al[92]	2021	Fusobacteria	16S rRNA seq	Gastric biopsy	Italy	55	32 controls	23 AG		No	Fusobacteria enriched in controls
Hsieh et al[87]	2022	F. nucleatum	TruSight Oncology 500 panel	Gastric tissue	Taiwan	36			36 GC	Yes	F. nucleatum and high tumour mutation burden are associated with poor prognosis	Prognosis
Chen et al[93]	2022	F. nucleatum	qPCR	Saliva	China	232	20 normal controls; 35 gastritis; 26 gastric polyps	31 AG	120 GC	Yes	F. nucleatum in saliva as biomarker for GC	Diagnosis	↑
Liu et al[94]	2022	Fusobacterium	16S rRNA seq	Gastric biopsy	Columbia, China, Italy, Mexico, South Korea	1270	109 healthy controls, 183 gastritis	135 AG; 124 IM, 94 IN	344 GC; 281 GC adj	Yes	Fusobacterium enriched in GC		↑
Aziz et al[85]	2022	F. nucleatum	Mass spectrometry	Gastric biopsy	Pakistan	75	12 normal controls, 38 gastritis, 12 ulcers		13 GC	Yes	Protein of F. nucleatum detectable in GC and gastritis
Zhang et al[81]	2022	Fusobacterium	16S rRNA seq	Saliva, stool, GC tissues	China	146	70 healthy controls		76 GC	Yes	Fusobacterium enriched in GC stool and saliva sample		↑
Li et al[95]	2022	Fusobacteria	16S rRNA seq	Saliva, esophageal swab, gastric juice, gastric biopsy, stool sample	China	40	22 healthy controls, 18 esophagitis			No	Fusobacteria in ~3% in all regions except faeces
Lehr et al[83]	2023	F. nucleatum	16S rRNA seq	Gastric tissue	Lithuania	64			64 GC + Adj	Yes	Higher abundance of F. nucleatum in GC tumour tissue associated with poorer survival; microbial network	Prognosis
Liu et al[89]	2023	F. nucleatum	qPCR	Gastric tissue	China	91			91 GC	Yes	Fusobacterium nucleatum conditions megakaryocytes by induction of extracellular vesicles
Wei et al[73]	2023	Fusobacterium	16S rRNA seq	Gastric juice	China	139	61 healthy controls		78 GC	Yes	Fusobacterium enriched in advanced GC		↑
Nikitina et al[46]	2023	Fusobacterium	16S rRNA seq	Gastric biopsy	Lithuania	105	29 healthy controls		76 GC	Yes	Fusobacterium abundance increased in tumour DNA versus RNA
Jeong et al[96]	2024	Fusobacteria	Whole metagenome shotgun sequencing	Stool sample	Taiwan	65	33 gastritis		32 GC	Yes	Fusobacteria enriched in GC		↑
Meng et al[90]	2024	F. nucleatum	16S rRNA seq	Gastric tissue	China	30			30 GC + Adj	Yes	F. nucleatum is more abundant in tumor than in adjacent samples and extracellular vesicles of F. nucleatum promote the growth of GC tumors and metastasis in the liver

GC: Gastric cancer; IM: Intestinal metaplasia; AG: Atrophic gastritis; PPI: Proton pump inhibitors; CRC: Colorectal cancer; H. pylori: Helicobacter pylori; F. nucleatum: Fusobacterium nucleatum.