Exploring the antidepressant mechanisms of Guipi pill: A focus on gut-brain axis and immunity modulation

Table 1 The detailed information of the platform

Series number	Platform	Number of patients	Number of healthy controls	Sample type
GSE10616	GPL5760 (Affymetrix GeneChip Human Genome U133 Plus 2.0 Array)	42	16	Ileum and colon
GSE20881	GPL1708 (Agilent-012391 Whole Human Genome Oligo Microarray G4112A)	99	73	Ileum and colon
GSE179285	GPL6480 (Agilent-014850 Whole Human Genome Microarray 4x44K G4112F)	223	31	Ileum and colon
GSE19738	GPL6848 (Agilent-012391 Whole Human Genome Oligo Microarray G4112A)	34	33	Whole blood
GSE52790	GPL17976 (hGlue_3_0_v1 Affymetrix Human hGlue_3_0_v1 Array)	12	10	Whole blood
GSE98793	GPL570 (HG-U133_Plus_2 Affymetrix Human Genome U133 Plus 2.0 Array)	64	128	Whole blood

Table 2 Constituents of Guipi pills

Chinese name	English name	Botanical plant name	Family and plant parts used	Processing method	Content (g)
Ren Shen	Ginseng	Panax ginseng C.A.Meyer	Root	Dry	6
Huang Qi	Astragalus	Astragalus membranaceus (Fisch.) Bunge	Root	Dry	12
Suan Zao Ren	Sour Jujube Seed	Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow	Fruit	Dry	12
Bai Zhu	White Atractylodes Rhizome	Atractylodes macrocephala Koidz	Root	Dry	9
Dang Gui	Dong Quai	Angelica sinensis (Oliv.) Diels	Root	Dry	9
Gan Cao	Licorice Root	Glycyrrhiza uralensis Fisch	Root	Dry	6
Yuan Zhi	Polygala Root	Polygala tenuifolia Willd	Root	Dry	3
Mu Xiang	Costus Root	Aucklandia lappa Decne	Root	Dry	6
LongYan Rou	Longan Fruit	Dimocarpus longan Lour	Fruit	Dry	12
Sheng Jiang	Ginger	Zingiber officinale Roscoe	Root	Dry	12
Fu Ling	Tuckahoe	Poria cocos (Schw.) Wolf	Sclerotium	Dry	9
Da Zao	Jujube	Ziziphus jujuba Mill	Fruit	Dry	12

Table 3 Venny analysis of the differentially expressed genes between inflammatory bowel disease patients and depression patients

Number	Gene list
1	SLC22A4
2	CHGA
3	MMP9
4	IL1R2
5	GZMA
6	LCN2
7	TMEM45B
8	KLRB1
9	GIMAP7
10	F13A1
11	TBX21
12	B3GNT8
13	S100A12
14	GPR171
15	GZMK
16	KCNJ2
17	HLA-DRA
18	VDR
19	LAD1
20	PRSS3
21	EMP1
22	CD24
23	SLAMF7
24	ITM2C
25	BATF2
26	TCN1
27	OASL
28	CTSG
29	DNASE1 L3
30	CCR7

Table 4 Venny analysis of the differentially expressed genes from Guipi pills vs chronic unpredictable mild stress and differentially expressed genes from inflammatory patients and depression patients

Number	Gene list
1	BATF2
2	CTSG
3	GZMA
4	GZMK
5	KCNJ2
6	LAD1
7	LCN2

Table 5 Mendelian randomization analysis of the genes GZMA, GZMK, and KCNJ2

Gene	NSNP	Method	B	SE	OR	OR_lci95	OR_uci95	P value
GZMA	7	MR Egger	-0.09239	0.078431	0.911751	0.781834	1.063256	0.291817
GZMA	7	Weighted median	-0.08458	0.053111	0.918895	0.82805	1.019706	0.111255
GZMA	7	Inverse variance weighted	-0.12065	0.041886	0.886347	0.816488	0.962183	0.003972
GZMA	7	Simple mode	-0.21042	0.087087	0.810241	0.683101	0.961046	0.052129
GZMA	7	Weighted mode	-0.07722	0.058268	0.925688	0.825784	1.037679	0.233323
GZMK	11	MR Egger	-0.02138	0.083978	0.978844	0.830291	1.153977	0.804737
GZMK	11	Weighted median	-0.01697	0.034472	0.983177	0.918942	1.051902	0.622597
GZMK	11	Inverse variance weighted	-0.00035	0.030074	0.999651	0.94243	1.060346	0.990735
GZMK	11	Simple mode	0.069455	0.064164	1.071923	0.945248	1.215574	0.304464
GZMK	11	Weighted mode	-0.02461	0.038771	0.975686	0.90429	1.052719	0.539766
KCNJ2	10	MR Egger	-0.0695	0.060344	0.932864	0.828805	1.049987	0.28271
KCNJ2	10	Weighted median	-0.05446	0.037879	0.946994	0.879234	1.019977	0.150487
KCNJ2	10	Inverse variance weighted	-0.05834	0.03037	0.943326	0.888812	1.001183	0.054721
KCNJ2	10	Simple mode	-0.04438	0.05821	0.956592	0.853448	1.072201	0.465342
KCNJ2	10	Weighted mode	-0.05748	0.042219	0.944141	0.869159	1.025592	0.206474

NSNP: Number of single nucleotide polymorphism; OR: Odds ratio.