General Information of MIC (ID: MIC00418)
MIC Name	Clostridium sp. (firmicutes)
MIC Synonyms	Anaerobacter sp.
Body Site	Gut
Lineage	Kingdom: Bacteria Phylum: Firmicutes Class: Clostridia Order: Clostridiales Family: Clostridiaceae Genus: Clostridium Species: Clostridium sp.
Oxygen Sensitivity	Obligate anaerobe
Microbial Metabolism	Saccharolytic; Fermentative
Gram	Positive
Host Relationship	Commensal
Description	Clostridium sp. is a obligate anaerobic, Gram positive species of genus Clostridium. It is part of the intestinal indigenous microbiota and they can produce several endogenous infections.
External Links	Taxonomy ID	1506
	GOLD Organism ID	Go0002030
Disease Relevance
Autism spectrum disorder  [ICD-11: 6A02]
Description	Clostridium spp. was significantly elevated in autistic children.				[1]
Autoimmune liver disease  [ICD-11: DB96]
Description	Clostridium was associated with primary sclerosing cholangitis.				[2]
Botulism  [ICD-11: 1A11]
Description	Pathogenic Clostridium spp. have been known to be responsible for Botulism.				[3]
Clostridium difficile enterocolitis  [ICD-11: 1A04]
Description	Pathogenic Clostridium spp. have been known to be responsible for Pseudomembranous colitis.				[3]
Colon cancer  [ICD-11: 2B90]
Description	Clostridium is downregulated in expression of Colon cancer.				[4]
Depression  [ICD-11: 6A70]
Description	Clostridium was identified by more than one report as elevated in major depressive disorder.				[5]
Diseases of coronary artery  [ICD-11: BA8Z]
Description	Clostridium sp. was associated with coronary heart disease.				[6]
Gas gangrene  [ICD-11: 1C16]
Description	Pathogenic Clostridium spp. have been known to be responsible for Gas gangrene.				[3]
Inflammatory bowel disease  [ICD-11: DD72]
Description	Faecal samples in inflammatory bowel disease were characterised by lower phylotype richness and proportions of Clostridiales.				[7]
Irritable bowel syndrome  [ICD-11: DD91]
Description	The level of Clostridium was significantly increased in irritable bowel syndrome patients than in healthy controls				[8]
Tetanus  [ICD-11: 1C13]
Description	Pathogenic Clostridium spp. have been known to be responsible for Tetanus.				[3]
Ulcerative colitis  [ICD-11: DD71]
Description	Clostridium was associated with ulcerative colitis regardless of the presence or absence of concomitant IBD.				[2]

Host Genetic Factors (HGFs)
15q11-13
HGF ID	HGF2318	HGF Info	Class	Copy Number Variation: Gene Duplication (CNV-GDu)
Description	There has a significantly different abundance of Clostridium sp. A9 between 15q dup mice and wide type littermates (p-value=0.0425).				[9]
VIPR2
HGF ID	HGF2350	HGF Info	Class	Copy Number Variation: Gene Deletion (CNV-GDe)
Description	The deletion of VIPR2 has been associated with the increased abundance of Clostridium.				[10]
CD160
HGF ID	HGF2314	HGF Info	Class	Copy Number Variation: Gene Duplication (CNV-GDu)
Description	The gene CD160 with exon duplications was significantly associated with decreased abundance of the Clostridiales.				[11]
RNF115
HGF ID	HGF2315	HGF Info	Class	Copy Number Variation: Gene Duplication (CNV-GDu)
Description	The gene RNF115 with exon duplications was significantly associated with decreased abundance of the Clostridiales.				[11]
RPS3A
HGF ID	HGF2317	HGF Info	Class	Copy Number Variation: Gene Duplication (CNV-GDu)
Description	The gene RPS3A with exon duplications was significantly associated with decreased abundance of the Clostridiales.				[11]
ARNTL
HGF ID	HGF2325	HGF Info	Class	Copy Number Variation: Gene Deletion (CNV-GDe)
Description	The deletion of BMAL1 could significantly increase relative abundances of Clostidiales spp. (p-value<0.05).				[12]
SLC15A1
HGF ID	HGF2354	HGF Info	Class	Copy Number Variation: Gene Deletion (CNV-GDe)
Description	The deletion of PepT1 could decrease the abundance of Clostridiales.				[13]
rs112294212
HGF ID	HGF1894	HGF Info	Class	Single Nucleotide Polymorphism: Intron variant (SNP-IV)
Description	The rs112294212 SNP was significantly associated with the relative abundance of Clostridium (p-value=8.39E-09).				[14]
rs748841
HGF ID	HGF1688	HGF Info	Class	Single Nucleotide Polymorphism: Intron variant (SNP-IV)
Description	The rs748841 SNP is significantly associated with the abundance of Clostridiales (p-value=1.46E-04).				[11]
rs3733890
HGF ID	HGF1908	HGF Info	Class	Single Nucleotide Polymorphism: Missense variant (SNP-MV)
Description	The rs3733890 SNP was significantly associated with the abundance of Clostridiales (p-value=2.77E-07).				[15]
rs2293702
HGF ID	HGF1370	HGF Info	Class	Single Nucleotide Polymorphism: Intron variant (SNP-IV)
Description	The rs2293702 SNP was significantly associated with the abundance of Clostridiales (p-value=1.41E-08).				[15]
rs2007084
HGF ID	HGF1926	HGF Info	Class	Single Nucleotide Polymorphism: Intron variant (SNP-IV)
Description	The rs2007084 SNP was significantly associated with the abundance of Clostridiales (p-value=2.15E-07).				[15]
rs1346183
HGF ID	HGF1613	HGF Info	Class	Single Nucleotide Polymorphism: Intron variant (SNP-IV)
Description	The rs1346183 SNP was significantly associated with the abundance of Clostridiales (p-value=3.21E-08).				[15]
rs10128711
HGF ID	HGF1318	HGF Info	Class	Single Nucleotide Polymorphism: Intron variant (SNP-IV)
Description	The rs10128711 SNP was significantly associated with the abundance of Clostridiales(p-value=5.18E-05).				[16]

Host Immune Factors (HIFs)
Tumor necrosis factor ligand superfamily member 15
HIF ID	HIFM0224	HIF Info	Class	Checkpoint molecule (CM)
Description	Clostridium was associated with TL1A.				[17]
Interferon-10
HIF ID	HIFM0128	HIF Info	Class	Cytokine (Cyt)
Description	The increasing levels of unclassified Ruminococcaceae (also of the Clostridiales order) correlated negatively with expression of the pro-inflammatory cytokine IL-17.				[18]
Interferon-6
HIF ID	HIFM0151	HIF Info	Class	Cytokine (Cyt)
Description	The increased abundance of Clostridium is associated with the increased levels of IL-6 in non-alcoholic fatty liver disease.				[19]
Tumor necrosis factor
HIF ID	HIFM0226	HIF Info	Class	Cytokine (Cyt)
Description	Clostridium was associated with TNF-alpha.				[19]
Interferon gamma
HIF ID	HIFM0260	HIF Info	Class	Cytokine (Cyt)
Description	Clostridium was associated with TNF-Gamma.				[19]
Immunoglobulin E
HIF ID	HIFM0271	HIF Info	Class	Immunoglobulin (Ig)
Description	Clostridiales could suppress the IgE anti-bacterial response.				[20]
Immunoglobulin A
HIF ID	HIFM0272	HIF Info	Class	Immunoglobulin (Ig)
Description	Clostridium was significantly enriched in the IgA(Low or no IgA binding) consortia.				[21]
Regulatory T cells
HIF ID	HIFC0030	HIF Info	Class	T cells (TCs)
Description	Clostridiales has the potential to induce Tregs immunity response.				[18]
CD4+ regulatory T cells
HIF ID	HIFC0034	HIF Info	Class	T cells (TCs)
Description	Clostridium spp.induced CD4+ regulatory T cells in the intestine and ameliorated intestinal inflammation in a murine model of IBD.				[22]
RORt+ regulatory T cells
HIF ID	HIFC0038	HIF Info	Class	T cells (TCs)
Description	Clostridiales plays an important role in nascent Treg cells that gives rise to disease-suppressing ROR-t+ Treg cells.				[20]
CD4+ T cells
HIF ID	HIFC0069	HIF Info	Class	T cells (TCs)
Description	Clostridium is associated with CD4+ T lymphocytes responses.				[19]
CD8+ T cells
HIF ID	HIFC0073	HIF Info	Class	T cells (TCs)
Description	Clostridium is associated with CD8+ T lymphocytes responses.				[19]
Foxp3+CD4+ T cells
HIF ID	HIFC0156	HIF Info	Class	T cells (TCs)
Description	Clostridium species can induce mucosal Foxp3+CD4+ T cells.				[23]

Environmental Factor(s)
Disbiome ID			9
gutMDisorder ID			gm0210

References
1	The Possible Role of the Microbiota-Gut-Brain-Axis in Autism Spectrum Disorder. Int J Mol Sci. 2019 Apr 29;20(9):2115. doi: 10.3390/ijms20092115.
2	Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. World J Gastroenterol. 2017 Jul 7;23(25):4548-4558. doi: 10.3748/wjg.v23.i25.4548.
3	Antimicrobial production by strictly anaerobic Clostridium spp. Int J Antimicrob Agents. 2020 May;55(5):105910. doi: 10.1016/j.ijantimicag.2020.105910. Epub 2020 Jan 25.
4	The human gutome: nutrigenomics of the host-microbiome interactions. OMICS. 2011 Jul-Aug;15(7-8):419-30. doi: 10.1089/omi.2010.0109. Epub 2010 Dec 1.
5	Systematic Review of Gut Microbiota and Major Depression. Front Psychiatry. 2019 Feb 11;10:34. doi: 10.3389/fpsyt.2019.00034. eCollection 2019.
6	Integrated metabolomics and metagenomics analysis of plasma and urine identified microbial metabolites associated with coronary heart disease. Sci Rep. 2016 Mar 2;6:22525. doi: 10.1038/srep22525.
7	Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut. 2017 May;66(5):863-871. doi: 10.1136/gutjnl-2015-309940. Epub 2016 Feb 4.
8	Identification of Gut Microbiota and Metabolites Signature in Patients With Irritable Bowel Syndrome. Front Cell Infect Microbiol. 2019 Oct 18;9:346. doi: 10.3389/fcimb.2019.00346. eCollection 2019.
9	Altered microbiota composition reflects enhanced communication in 15q11-13 CNV mice.Neurosci Res. 2019 Dec 18:S0168-0102(19)30671-6. doi: 10.1016/j.neures.2019.12.010. Online ahead of print.
10	Association of gut microbiota composition and copy number variation with Kasai procedure outcomes in infants with biliary atresia.Pediatr Neonatol. 2020 Apr;61(2):238-240. doi: 10.1016/j.pedneo.2019.12.011. Epub 2020 Jan 7.
11	Whole exome sequencing analyses reveal gene-microbiota interactions in the context of IBD.Gut. 2020 Jul 10:gutjnl-2019-319706. doi: 10.1136/gutjnl-2019-319706. Online ahead of print.
12	Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock.Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10479-84. doi: 10.1073/pnas.1501305112. Epub 2015 Aug 3.
13	Impact of PepT1 deletion on microbiota composition and colitis requires multiple generations.NPJ Biofilms Microbiomes. 2020 Jul 21;6(1):27. doi: 10.1038/s41522-020-0137-y.
14	Association of host genome with intestinal microbial composition in a large healthy cohort.Nat Genet. 2016 Nov;48(11):1413-1417. doi: 10.1038/ng.3693. Epub 2016 Oct 3.
15	Genetic Determinants of the Gut Microbiome in UK Twins.Cell Host Microbe. 2016 May 11;19(5):731-43. doi: 10.1016/j.chom.2016.04.017.
16	The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids.Circ Res. 2015 Oct 9;117(9):817-24. doi: 10.1161/CIRCRESAHA.115.306807. Epub 2015 Sep 10.
17	TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory System of Cytokines With Diverse Functions in Gut Mucosal Immunity.Front Immunol. 2019 Mar 27;10:583. doi: 10.3389/fimmu.2019.00583. eCollection 2019.
18	Expression of immune regulatory genes correlate with the abundance of specific Clostridiales and Verrucomicrobia species in the equine ileum and cecum. Sci Rep. 2019 Sep 3;9(1):12674. doi: 10.1038/s41598-019-49081-5.
19	Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Sci Rep. 2015 Feb 3;5:8096. doi: 10.1038/srep08096.
20	Microbiota therapy acts via a regulatory T cell MyD88/RORt pathway to suppress food allergy. Nat Med. 2019 Jul;25(7):1164-1174. doi: 10.1038/s41591-019-0461-z. Epub 2019 Jun 24.
21	IgA Function in Relation to the Intestinal Microbiota.Annu Rev Immunol. 2018 Apr 26;36:359-381. doi: 10.1146/annurev-immunol-042617-053238. Epub 2018 Jan 26.
22	Commensal bacteria calibrate the activation threshold of innate antiviral immunity.Immunity. 2012 Jul 27;37(1):158-70. doi: 10.1016/j.immuni.2012.04.011. Epub 2012 Jun 14.
23	Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10-producing regulatory B cells.J Clin Invest. 2019 Jun 18;129(9):3702-3716. doi: 10.1172/JCI93820.

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