Multi-omics analysis of fecal microbiota transplantation's impact on functional constipation and comorbid depression and anxiety

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-16
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Yang C, Hu T, Xue X, Su X, Zhang X, Fan Y, Shen X, Dong X
Journal
BMC microbiology
Year
2023
Keywords:
5-hydroxytryptamine, Constipation, Depression and anxiety, Fecal microbiota transplantation, Metabolomics, Metagenomics
BACKGROUND: Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted. METHODS: We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro. RESULTS: Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells. CONCLUSION: FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/04/16

Curator: Shulamite

Revision editor(s): Shulamite, Anne-mariesharp

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to transplant Response to transplant,response to transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Fb (Patients before FMT - Fecal microbiota transplantation)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Fa (Patients After FMT - Fecal microbiota transplantation)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with functional constipation and comorbid depression/anxiety after undergoing fecal microbiota transplantation (FMT).
Group 0 sample size Number of subjects in the control (unexposed) group
4
Group 1 sample size Number of subjects in the case (exposed) group
4
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 weeks

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Kruskall-Wallis
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/04/17

Curator: Shulamite

Revision editor(s): Shulamite, Anne-mariesharp

Source: Fig 2C

Description: The shift in gut microbiota before and after FMT based on metagenomic sequencing data.

Abundance in Group 1: increased abundance in Fa (Patients After FMT - Fecal microbiota transplantation)

NCBI Quality ControlLinks
Enterococcus hermanniensis

Revision editor(s): Shulamite, Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/04/17

Curator: Shulamite

Revision editor(s): Shulamite, Anne-mariesharp

Source: Fig 2E

Description: The shift in gut microbiota before and after FMT based on metagenomic sequencing data.

Abundance in Group 1: decreased abundance in Fa (Patients After FMT - Fecal microbiota transplantation)

NCBI Quality ControlLinks
Bacteroides pyogenes

Revision editor(s): Shulamite, Anne-mariesharp

Experiment 4


Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/04/17

Curator: Shulamite

Revision editor(s): Shulamite, Anne-mariesharp

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/04/17

Curator: Shulamite

Revision editor(s): Shulamite, Anne-mariesharp

Source: Table S2 and Table 3

Description: Differential relative abundance of species between the Fb and Fa groups

Abundance in Group 1: increased abundance in Fa (Patients After FMT - Fecal microbiota transplantation)

NCBI Quality ControlLinks
Acetobacterium bakii
Allofournierella massiliensis
Anaeromassilibacillus senegalensis
Anaeromassilibacillus sp. An200
Anaeromyces robustus
Anaerotignum neopropionicum
Anaerovibrio lipolyticus
Anaerovirgula multivorans
Angelakisella massiliensis
Bacillus wiedmannii
Bacteroidales bacterium 55_9
Bacteroides sp. 2_1_22
Bifidobacterium sp. N4G05
Brevibacillus laterosporus
Butyrivibrio sp. AE2032
Butyrivibrio sp. NC2002
Candidatus Marispirochaeta associata
Cloacibacillus evryensis
Cloacibacillus porcorum
Clostridiales bacterium 59_14
Clostridiales bacterium VE202-13
Clostridium formicaceticum
Clostridium sp. CAG:169
Clostridium sp. CAG:217_53_7
Clostridium sp. CAG:253
Clostridium sp. CAG:302
Clostridium sp. CAG:448
Clostridium sp. HGF2
Clostridium sp. MD294
Clostridium sp. W14A
Cohnella sp. OV330
Collinsella sp. An268
Curtobacterium sp. ER1/6
Dehalobacterium formicoaceticum
Desulfotomaculum nigrificans
Drancourtella massiliensis
Enterococcus hermanniensis
Erysipelotrichaceae bacterium 5_2_54FAA
Faecalibacterium sp. CAG:1138
Fibrobacter sp. UWB3
Firmicutes bacterium CAG:24053_14
Firmicutes bacterium CAG:882
Flavobacterium psychrophilum
Flavonifractor sp. An91
Gemmiger formicilis
Gemmiger sp. An87
Gorillibacterium massiliense
Lachnospira pectinoschiza
Lachnospiraceae bacterium A10
Lachnospiraceae bacterium C10
Lactiplantibacillus plantarum
Lactobacillus acidophilus
Lactobacillus gallinarum
Laribacter hongkongensis
Leptotrichia sp. oral taxon 879
Leuconostoc citreum
Limosilactobacillus coleohominis
Lysinibacillus sphaericus
Marinimicrobium agarilyticum
Massilimicrobiota sp. An105
Massilimicrobiota sp. An80
Mediterraneibacter gnavus
Megasphaera massiliensis
Mitsuokella multacida
Nitrolancea hollandica
Orenia metallireducens
Oribacterium sinus
Oribacterium sp. oral taxon 078
Oribacterium sp. oral taxon 108
Oscillibacter ruminantium
Oscillibacter sp. 1-3
Oscillibacter sp. ER4
Paenibacillaceae bacterium ZCTH02-B3
Paenibacillus amylolyticus
Paenibacillus apiarius
Paenibacillus chondroitinus
Peptococcaceae bacterium 1109
Prevotella falsenii
Prevotella sp. CAG:474
Propionispira arboris
Propionispora sp. 2/2-37
Pyramidobacter sp. C12-8
Ruminococcaceae bacterium D16
Ruminococcaceae bacterium cv2
Ruminococcus sp. CAG:353
Ruthenibacterium lactatiformans
Schwartzia succinivorans
Selenomonas artemidis
Selenomonas bovis
Selenomonas sp. FC4001
Selenomonas sp. oral taxon 136
Sporomusa sphaeroides
Staphylococcus hominis
Streptococcus cristatus
Streptococcus ilei
Streptococcus oralis
Streptococcus ovis
Streptococcus sp. HSISS3
Streptococcus vestibularis
Subdoligranulum sp. 4_3_54A2FAA
Subdoligranulum sp. 60_17
Subdoligranulum variabile
Traorella massiliensis
[Clostridium] hylemonae
bacterium OL-1
uncultured bacterium EB5

Revision editor(s): Shulamite, Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/04/17

Curator: Shulamite

Revision editor(s): Shulamite, Anne-mariesharp

Source: Table S2 and Table 3

Description: Differential relative abundance of species between the Fb and Fa groups

Abundance in Group 1: decreased abundance in Fa (Patients After FMT - Fecal microbiota transplantation)

NCBI Quality ControlLinks
Acidiphilium sp. CAG:727
Bacillus sp. BO
Bacillus sp. UNC41MFS5
Bacteroides faecichinchillae
Bacteroides faecis CAG:32
Bacteroides pyogenes
Bacteroides sp. An51A
Bacteroides stercorirosoris
Bacteroides thetaiotaomicron
Blautia sp. An81
Caloranaerobacter sp. TR13
Clostridium botulinum
Clostridium sp. D5
Dehalobacterium formicoaceticum
Escherichia coli
Faecalicatena contorta
Klebsiella pneumoniae
Klebsiella sp. HMSC16C06
Klebsiella variicola
Lachnospiraceae bacterium 2_1_58FAA
Lachnospiraceae bacterium 6_1_37FAA
Listeria monocytogenes
Mediterraneibacter gnavus
Mediterraneibacter gnavus CAG:126
Natronincola peptidivorans
Odoribacter splanchnicus
Paenibacillus algorifonticola
Paenibacillus ferrarius
Parabacteroides gordonii
Peptostreptococcus russellii
Pseudobutyrivibrio sp. UC1225
Pyramidobacter sp. C12-8
Shigella genomosp. SF-2015
Shigella sonnei
Slackia sp. CM382

Revision editor(s): Shulamite, Anne-mariesharp