Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis

Wu, Zihong; Huang, Yuqing; Zhang, Renyi; Zheng, Chuan; You, Fengming; Wang, Min; Xiao, Chong; Li, Xueke

doi:10.1186/s12964-024-01549-2

Cell Communication and Signaling

Table 2 Summary of sexual dimorphism in the gut microbiome in CRC

From: Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis

Model organism	Sex dimorphism	Change in Gut microbiome		Findings	References
Model organism	Sex dimorphism	Increase (Enrich)	Reduce	Findings	References
CRC/adenoma patients	male	F.mortiferum, B. adolescentis, S. hippei, P. gingivalis, A. intestini, Clostridium sp. AT4, D. propionicifacien, M. smithii, B. massiliensis, F. varium, L. bacterium		The composition and relative abundance of the gut microbiome in CRC would be influenced by sex	[80]
CRC/adenoma patients	female	Prevotella sp. Marseille, C. colinum, B. pseudocatenulatum, Gordonibacter sp. Marseille, C. Saccharibacteria			[80]
	male	Bacteroides, Eubacterium, Faecalibacterium			[81]
	female	Bacteroides, Subdoligranulum, Eubacterium			[81]
CRC/adenoma patients	male	microbial β-diversity, rare species, more stochastic community structure		The gut microbial communities are more stable in males than in females during the development of CRC	[82]
CRC/adenoma patients	female	more deterministic community structure	microbial α- and β-diversity, key species		[82]
Patients with pks + E. coli	male	pks + E. coli		The prevalence of pks + E. coli was significantly higher in men than women	[83]
Patients with pks + E. coli	female	pks + E. coli			[83]
CRC patients	female	F. nucleatum		Women are more susceptible to F. nucleatum following Vitamin D supplementation	[84]
Adenoma patients	male	F. prausnitzii	R. gnavus	Gender alters UDCA activity in the CRC	[87]
	female	no difference		Gender alters UDCA activity in the CRC	[87]
Min/+ and AOM/DSS mice	male	C.aerofaciens, D. bacterium, A. muciniphila, A. inops	P. goldsteinii, L.taiwanensis, L. fermentum	Gender-biased gut microbiome and metabolites favor sex dimorphism in CRC	[89]
Min/+ and AOM/DSS mice	female	microbial diversity, beneficial bacteria	harmful bacteria		[89]
AOM/DSS mice	E2-treated male	microbial diversity	Bacteroides, F/B ratio	E2 may induce changes in the gut microbiota, thereby reducing the risk of CRC	[90]
	male	C/O ratio
	female_OVX		C/O ratio
MC38 tumor model mice	αPD-L1 + E2 male	family Ruminococcaceae, L. murinus group and P. goldsteinii	family Muribaculaceae, Enterobacteriaceae group	E2 pre-treatment prior to anti-PD-L1 therapy induces changes in the gut microbiome of MC38 mice, thereby contributing to anti-tumor therapy	[92]
	αPD-L1 male	P. goldsteinii
	αPD-L1 female	P. goldsteinii
AOM/DSS mice	male	Parasutterella	microbiota diversity	ERβ facilitates a more favorable gut microbiome, which may prevent the development of CRC	[93]
	fenale	Prevotellaceae_UCG_001	microbiota diversity
	ERβ_KO	Rikenellaceae_RC9; Lachnospiracae_UCG_010	microbiota α- diversity, Chao-1index
AOM/DSS mice	male	A. muciniophila; B. vulgatus	microbiota α- diversity	Alterations in intestinal flora composition by Nrf2 depend on gender and CRC induction	[94]
	female	B. abundance	L. murinus
	male Nrf2_KO	A. muciniophila	microbial α-diversity, L. murinus
	female Nrf2_ KO	No difference
AOM/DSS mice	male_ORX	microbial diversity; F/B ratio		Testosterone-induced dysbiosis of the gut microbiota may be a factor in sex differences in colorectal carcinogenesis	[95]
	Male_ORX + TP		microbial diversity, F/B ratio; C/O ratio
	TP- male and female	opportunistic pathogens (M. schaedleri or A. muciniphila)	C/O ratio
	female	microbial diversity, beneficial bacteria	harmful bacteria
MC38 tumor model mice	male	Family Muribaculaceae	microbial α-diversity, Lachnospiraceae group	Sex differences in the gut microbiota should be considered when applying antibiotics for the treatment of immune checkpoint inhibitor-associated colitis	[96, 97]
MC38 tumor model mice	female	Lachnospiraceae group	microbial α-diversity, Family Muribaculaceae		[96, 97]
AOM/DSS mice	ZEA⁺ male	unidentified Ruminococcaceae, Parabacteroidies, Blautia; microbial community stability	Microbial community vulnerability	Zearalenone increases SCFAs-producing intestinal microbiome with good inhibitory effects on CRC	[100]
Smad3^−/− CAC model	SFB⁺male	Helicobacter spp., SFB		SFB has a sex-dependent protective effect in CRC male mice	[102]
Smad3^−/− CAC model	SFB⁺female	Helicobacter spp., SFB, family Enterobacteriaceae		SFB has a sex-dependent protective effect in CRC male mice	[102]

AOM/DSS Azoxymethane/dextran sodium sulfate, CRC Colorectal cancer, C/O Commensal bacteria/opportunistic pathogens, E2 Estradiol/17β-estradiol, ERβ Estrogen receptor-beta, F/B Firmicutes/Bacteroidetes, OVX Ovariectomy, ORX Orchiectomy, pks + E. coli Escherichia coli containing polyketide synthase, SCFAs Short chain fatty acids, SFB Segmented Filamentous Bacteria, TP Testosterone propionate, UDCA Ursodeoxycholic acid, ZEA Zearalenone

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ISSN: 1478-811X

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