Table 2.

The negative effects of A. muciniphila on intestinal disease in some special cases.

Author/Year	Object	Model	Experimental design	Negative effect
Mahesh S. Desai et al.15	Mouse	Low-fiber diet and pathogen infection	Gnotobiotic mice are constructed with a synthetic gut microbiota from fully sequenced human gut bacteria, fed a fiber-deprivation diet (chronic or intermittent) and used Citrobacter rodentium to infect mice with two diet models to investigate the mechanistic connections between dietary fiber deficiency and microbiota composition, as well as the resulting effects on the mucus barrier.	Low-fiber diet promotes expansion and activity of mucus-degrading bacteria, such as A. muciniphila, which alleviates the degradation of the mucus layer and increases the susceptibility of pathogen-associated colitis.
Sergey S. Seregin et al.17	Mouse	Immune deficiency disorders associated with IBD	16 S rRNA sequencing is used to analyze the change of gut microbiota in Il10−/− mice with spontaneous colitis and innate immune receptor NLRP6 deficiency, and oral gavage of screened strains is performed to investigate its effects in these mice.	1. The relative abundance of A. muciniphila is significantly increased in Il10−/− Nlrp6−/− mice. 2. A. muciniphila promotes colitis represented by the decreasing of body weight, as well as the increase of the colonic histological scores, weight of spleen, inflammation indication of colon, level of fecal Lcn-2, bacterial translocation to MLNs and pro-inflammatory mediators in the colons of both SPF Il10−/− mice and germ-free Il10−/− mice.
Héctor Argüello et al.131	Pig	S. typhimurium infection	16 S rRNA sequencing is used to analyze the composition of mucosa microbiome in the ileum of 28 days old pigs with S. typhimurium infection.	1. Genus Akkermansia increases within the mucosa of the S. typhimurium infected pigs. 2. Epithelial damage is positively correlated to taxa belonging to the phyla Verrucomicrobia such as A. muciniphila.
Bhanu Priya Ganesh et al.16	Mouse	S. typhimurium infection	Oral gavage of A. muciniphila followed by subsequently infection of S. typhimurium in gnotobiotic C3H mouse model with a background microbiota of eight bacterial species to research the impact of A. muciniphila on inflammatory and infectious symptoms.	1. After 5 days infection, S. typhimurium become the predominant species representing 94.03% of total bacteria in the cecum of mice co-colonized by A. muciniphila and S. typhimurium. 2. Co-colonization of A. muciniphila and S. typhimurium causes significantly higher histological scores and elevates the mRNA levels of pro-inflammatory cytokines, especially IFN-γ, IP-10, TNF-α, IL-12, IL-6, IL-17 in the cecum and colon of the infected mice. 3. The number of mucin-filled goblet cells, the thickness of mucus and mucus sulphation are significantly decreased by the co-colonization of A. muciniphila and S. typhimurium. 4. The existence of A. muciniphila may induce the deeper colonization of S. typhimurium in cecal tissue and encourages the recruitment of macrophages into the cecal lamella propria and submucosa.
Nielson T Baxter et al.122	Mouse	CRC	The fecal microbiota from three CRC patients and three healthy individuals are transplanted into germ-free mice, respectively. then, these mice are chemically induced to CRC resulting in different levels of tumorigenesis. The change of gut microbiome is investigated using 16 S rRNA sequencing and metagenomic analysis.	The taxa most strongly positively correlate with increased tumor burden are several Gram-negative species including Akkermansia.
Joseph P. Zackular et al.132	Mouse	CRC	The development of microbiome during the tumorigenesis in a mouse model with inflammation-driven colon cancer is investigated using 16 S rRNA sequencing.	1. Tumor-bearing mice show an enrichment in OTUs affiliated with members of Akkermansia. 2. The tumorigenesis in the colon of germ-free mice transplanted with the fecal microbiota from mice with tumor is increased.
Celia Dingemanse et al.123	Mouse	CRC	Shotgun metagenomic sequencing plus quantitative PCR is used to analyze the gut microbiota in intestine-specific conditional Apc mutant mice (FabplCre; Apc15lox/+) with large intestine tumor. Then, the FabplCre; Apc15lox/+ mice are treated with the identified specific bacteria by orally gavage to investigate their impact on the development of tumor.	1. Metagenomic sequencing shows that the genus Akkermansia is responsible for the overrepresentation in the conventional samples with more intestinal tumors. 2. The oral gavage of A. muciniphila to antibiotic-pretreated FabplCre; Apc15lox/+ mice significantly increases the number of intestinal tumors. 3. A. muciniphila significantly increases the thickness of intestinal mucus layer and the goblet cell ratio in FabplCre; Apc15lox/+ mice which may aggravate adenomatous in tumor-susceptive mice.