. 2023 Feb 8;28(1):1. doi: 10.1007/s40519-023-01529-4

Table 2.

Main characteristics of human studies included in the review

Author, year	Study design	Objectives	Sample characteristics	Treatment	Measures	Methods	Main results
Armougom et al., 2009 [39]	Cross-sectional	Identification of specific microbial communities associated with AN, OB, or NW	AN, n = 9 BMI:12.73 ± 1.602 Age: 19–36 OB, n = 20 BMI:47.09 ± 10.66 Age: 17–72 NW, n = 20 BMI:20.68 ± 2.014 Age: 13–68	n/a	Microbiological Assessment Bacteria copy number/ g of faeces	Real-time qPCR of microbiota species (stool sample)	↑ relative abundance of M. smithii in AN than in NW
Pfleiderer et al., 2013 [45]	Case Report	Culturomic analysis of AN stool samples	AN, n = 1 BMI: 10.4 Age: 21	n/a	Microbiological Assessment Bacterial identification	Mass spectrometry (MALDI-TOF) Culture Growth	Identification of 11 new bacterial species
Million et al., 2013 [41]	Cross-sectional	Comparison of faecal concentrations of Escherichia coli, M. smithii, Bifidobacterium animalis, and Lactobacillus spp in OB, OW, NW, and AN	AN, n = 15 BMI:13.5 (11.7–14.6) Age: 27.3 ± 10.8 NW, n = 76 BMI:22.4 (20.7–23.7) Age: 49.5 ± 18.6 OW, n = 38 BMI: 27.1 (25.9–28.6) Age: 54.1 ± 17.8 OB, n = 134 BMI: 40.0 (36.4–46.8) Age: 51.8 ± 14.7	n/a	Microbiological Assessment Prevalence of each bacterial taxonomic group Concentration (log10 copies of DNA / ml)	Real-time PCR of microbiota species (stool sample)	BMI was negatively correlated to M. smithii, E. coli, and B. animalis BMI was positively correlated to Lactobacillus reuteri
Morita et al., 2015 [43]	Cross-sectional	Comparison of intestinal microbiota composition in NW, ANBP, and ANR	ANR, n = 14 BMI: 12.7 ± 1.5 Age: 28.1 ± 10.7 ANBP, n = 11 BMI: 13.0 ± 1.2 Age: 32.5 ± 9.4 NW, n = 21 BMI: 20.5 ± 2.1 Age: 31.5 ± 7.4	n/a	Microbiological Assessment Prevalence of each bacterial taxonomic group log10 cells / g of faeces Biochemical parameters SCFAs	Yakult Intestinal Flora-SCAN (YIF-SCAN®): Reverse transcription-qPCR of microbiota species (stool sample) based on 16S and 23S rRNA analysis Biochemical analysis of blood samples High-performance liquid chromatography (HPLC) of stool samples	↓ bacterial count of Streptococcus, C. coccoides, C. leptum, B. fragilis, and L. plantarum in AN than in NW ↓ C. coccoides in ANR than in NW ↓ B. fragilis in ANR and ANBP than in NW ↓ acetic and propionic acid in AN than in NW No significant differences were found in butyrate concentrations between AN and NW
Kleiman et al., 2015 [34]	Longitudinal	Evaluation of changes to intestinal microbiota in AN patients after hospital-based weight restoration Comparison of intestinal microbiota composition in AN and in a normal weight group Assessment of the association between microbial composition, depression, anxiety, and eating disorder psychopathology	AN_0, n = 16 BMI: 16.2 ± 1.5 Age:28 ± 11.7 AN_1, n = 10 BMI: 17.4 ± 0.9 NW, n = 12 BMI: 21.5 ± 1.9 Age:29.8 ± 11.6	Duration Not specified Type of treatment Weight restoration Other unspecified pharmacological/psychological treatment	Microbiological Assessment Taxa relative abundance α-diversity (species richness, Chao-1 index) and β-diversity (UniFrac distances) Psychological assessment Specific psychopathological characteristics related to eating disorders and, anxious or depressive symptoms	16S rRNA sequencing (V1-V3) (stool sample) BAI, BDI, EDE-Q	↓ genera of Coriobacteriaceae, Parabacteroidetes and ↑ genera of Ruminococcaceae in AN₁ than NW ↑ Bacilli, Coriobacteriales and ↓ Clostridiales, Clostridia, Anaerostipes, Faecalibacterium in AN₀ than NW ↓ α-diversity in AN₀ and AN₁ than NW Significant difference in β-diversity between AN and NW that normalized after treatment α-diversity was negatively associated to EDE-Q total scores, BDI, and subscales scores for shape and weight concern
Mack et al., 2016 [35]	Longitudinal	Comparison of intestinal microbiota composition in AN and NW Evaluation of changes in microbiota composition in post-weight gain and/or normalisation of eating behaviour Assessment of SCFAs profiles (pre- and post-weight gain) dietary intake, and gastrointestinal symptoms	AN_0, n = 55 BMI: 15.3 ± 1.4 Age: 23.8 ± 6.8 AN_1, n = 44 BMI: 17.7 ± 1.4 NW, n = 55 BMI: 21.6 ± 2.0 Age: 23.7 ± 6,7	Duration 3,5 ± 1,7 months Type of treatment Weight restoration Normalized eating habits Other unspecified pharmacological/psychological treatment	Microbiological Assessment Relative abundance of bacterial taxa Prevalence of bacterial taxa α-diversity (Species richness, Chao-1 index, Shannon index) and β-diversity (unweighted UniFrac distance, Bray–Curtis dissimilarity) SCFAs Gastrointestinal symptoms	16S rRNA sequencing (V4) (stool sample) Gas chromatography Gastro-questionnaire	↓ Bacteroidetes to Firmicutes ratio in AN₀ than NW, further decreasing after treatment ↑ Actinobacteria in AN₀ than in NW ↑ Verrucomicrobia in AN₀ than in NW, normalizing after treatment AN₀ shows ↑ relative abundance of M. smithii (but ↓ prevalence), mucin degrading bacteria (Anaerostipes, Anaerotruncus, Akkermansia), Clostridium cluster I, XI, XVIII, and Bifidobacterium No significant differences in α-diversity between AN and NW Significantly lower β-diversity in the same AN individual at different times (AN₀-AN₁) than in different subjects in the respective groups ↑ valerate, iso-butyrate and, BFCAs concentrations in AN₀ and AN₁ as compred to NW
Mörkl et al., 2017 [44]	Cross-sectional	Comparison of intestinal microbiota in AN, AT, NW, OW, and OB groups	AN, n = 18 BMI: 15.3 ± 1.3 Age: 22.44 ± 3.20 AT, n = 20 BMI:22.14 ± 1.76 Age: 22.15 ± 3.86 NW, n = 26 BMI:21.89 ± 1.73 Age: 24.93 ± 3.75 OW, n = 22 BMI:26.99 ± 1.13 Age: 25.32 ± 3.98 OB, n = 20 BMI:34.55 ± 4.43 Age: 26.9 ± 6.10	n/a	Microbiological Assessment Relative abundance of bacterial taxa α-diversity (species richness, Chao-1 index, Shannon index) and β-diversity (weighted and unweighted UniFrac distance) Psychological assessment Depressive symptoms Anthropometric assessment (%) body fat Body fat distribution Biochemical Parameters	16S rRNA sequencing (V1-V2) (stool sample) BDI, HAMD BIA, ultrasound measurements	↑ Coriobacteriaceae in AN than in NW No significant differences in α- and β-diversity between AN and NW, but significant differences between AN and AT α-diversity was negatively correlated to BDI scores when all groups were included in the analysis
Borgo et al., 2017 [40]	Cross-sectional	Evaluation of the relationship between intestinal microbiota composition, nutritional status, and psychological characteristics in ANR	ANR, n = 15 BMI:13.82 ± 1.80 Age: 25.6 ± 7.97 NW, n = 15 BMI:22.06 ± 2.55 Age: 24.4 ± 5.79	n/a	Microbiological Assessment Relative abundance of bacterial taxa Prevalence of M. smithii M. smithii copy number α-diversity and β-diversity (OTU-based methods) Psychological assessment General psychopathology, typical cognitive and behavioural characteristics of eating disorders, and anxious or depressive symptoms SCFAs	16S rRNA sequencing (V3-V4) (stool sample) Real-time qPCR for M. smithii SCL-90, EDI-2, STAI-Y, BDI-II Gas chromatography	↓ Firmicutes, Ruminococcus, Roseburia, Clostridium, and ↑ Proteobacteria, Enterobacteriaceae in AN than NW ↑ prevalence and absolute abundance of M. smithii in AN than NW No significant differences in α- and β-diversity between AN and NW BMI was negatively associated to obsession-compulsion score (SCL-90), state anxiety score (STAI-Y), trait anxiety score (STAI-Y), and BDI total score Clostridium spp. was negatively correlated with BDI score ↓ butyrate and propionate levels in AN than in NW No differences in acetate, iso-valerate and iso-butyrate levels between AN and NW Butyrate was negatively correlated to depression and anxiety scores
Kleiman et al., 2017 [47]	Case series	Characterization of daily changes in intestinal microbiota composition and diversity in three acute AN patients during hospital-based renourishment	AN_0, n = 3 BMI: 15.6, 17.6,13.7 Age: 25,29,16 AN_1, BMI: 20.2, 21.1, 15.4	Duration Between 34 and 73 days Type of treatment Weight restoration Other unspecified pharmacological/psychological treatment	Microbiological Assessment Relative abundance of bacterial taxa α-diversity (Shannon index) and β-diversity (unweighted UniFrac distance) Biochemical parameters	16S rRNA sequencing (V4) (stool sample)	Patient-specific changes in intestinal microbiota composition and diversity during renourishment
Prochazkova et al., 2019 [46]	Case Report	Assessment of intestinal microbiota composition and microbial metabolites post FMT in a woman with AN Evaluation of the effects of FMT on the patient’s psychiatric conditions	AN, n = 1 BMI: 12.36 Age: 37 Healthy donor, n = 1 Age: 67	Type of treatment FMT	Microbiological Assessment Log10 copies 16S rRNA/40 ng gDNA Relative abundance of bacterial and fungal taxa α-diversity (species richness, Chao-1 index, Shannon index) and β-diversity (non-metric multidimensional scaling) Psychological assessment Psychiatric symptoms, family dynamics, and specific eating disorder symptoms SCFAs Metabolites of the tryptophan pathway in the intestine Intestinal permeability I-FABP levels	qPCR 16S rRNA sequencing (V4) and ITS fungal region sequencing (stool sample) EDE-Q, BAI, BDI II NMR, Mass spectrometry	Eating pattern, mood, and gastrointestinal complaints remain unchanged after FMT ↑ absolute abundance of A. muciniphila and M. smithii at 12 months post-FMT Significant changes in bacterial and fungal composition post-FMT ↑ α-diversity and SCFAs level post-FMT ↓ faecal serotonin level and intestinal permeability post-FMT
Monteleone et al., 2021a [36]	Longitudinal	Evaluation of intestinal microbiota composition in women with AN during weight restoration Evaluation of metabolomic changes in AN pre and post-weight restoration	AN_0, n = 21 BMI: 14.6 ± 1.3 Age: 21.7 ± 4.2 AN_1, n = 20 BMI: 20.5 ± 0.7 NW, n = 20 BMI: 20.3 ± 1.4 Age: 23.0 ± 3.3 NW_1, n = 16	Duration 5 months Type of treatment Nutritional Rehabilitation Enhanced Cognitive Behaviour Therapy 9 patients received SSRI	Microbiological Assessment Relative abundance of bacterial taxa α-diversity (Chao-1 index, Fisher index), and β-diversity (non-metric multidimensional scaling) Psychological assessment General psychopathology, and specific symptoms of eating disorders Metabolomic Analysis	16S rRNA sequencing (V4) (stool sample) EDE-Q, BSI, and SCL-90 gas chromatography–mass spectrometry system	↓ α-diversity in AN₀ than in NW, normalizing in AN₁ No significant difference in β-diversity between AN and NW ↑ Actinobacteria, Coprococcus, Weissella and ↓ Bacteroidetes, Firmicutes, Coriobacteriales, Oxalobacteriaceae, Parabacteroides in AN₀ than NW ↑ Firmicutes, Bacteroidetes, Leuconostocaceae and ↓ Actinobacteria, Coriobacteriales, Catabacteriaceae, Parabacteroidetes, Collinsella, Catabacter in AN₁ than NW Different bacterial taxa were significantly correlated to BMI, EDE-Q total score, and BSI total scores
Monteleone et al., 2021b [42]	Cross- sectional	Comparison of intestinal microbiota composition in NW, ANR, and ANBP Evaluation of the metabolomic profile and its associations with the intestinal microbiota in individuals with ANR and ANBP	ANR, n = 17 BMI: 15.0 ± 1.8 Age: 20.5 ± 3.1 ANBP, n = 6 BMI: 14.7 ± 1.5 Age: 25.2 ± 5.2 NW, n = 20 BMI: 20.3 ± 1.4 Age: 23.0 ± 3.3	n/a	Microbiological Assessment Relative abundance of bacterial taxa α-diversity (Chao-1 index) and β-diversity (non-metric multidimensional scaling) Metabolomic Analysis	16S rRNA (V4) sequencing (stool sample) Gas chromatography–mass spectrometry system	↑ Verrucomicrobia, and ↓ C. coccoides, B. fragilis in ANR as compared to NW ↓ Odoribacter, Eubacteriaceae in ANBP than NW ↓ Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales and ↑ Haemophilus, Pasteurellaceae, Pasteurellales in ANR than ANBP ↓ α-diversity in AN than NW No significant difference in β-diversity between AN and NW Significant differences in metabolomic levels between ANBP, ANR, and NW
Schulz et al., 2021 [38]	Longitudinal	Comparison of intestinal microbiota composition and diversity in adolescents with AN and age-matched NW individuals Evaluation of intestinal microbiota composition and diversity in AN adolescents during pre and post-weight recovery	AN_0, n = 19 BMI:15.76 ± 2.03 Age: 15.77 ± 1.94 AN_1, n = 19 BMI: 18.8 ± 0.87 NW, n = 20 BMI:20.31 ± 2.35 Age: 16.35 ± 1.11	Duration 4.05 ± 1.39 months Type of treatment Weight restoration Individual and group psychotherapy, parent psychoeducation and training, occupational-, music- and physical therapy	Microbiological Assessment Relative abundance of bacterial taxa α-diversity (Species richness, Chao-1 index, Shannon index) and β-diversity (Bray–Curtis and Jaccard) Psychological assessment Specific characteristics of eating disorders, and anxious or depressive symptoms	16S rRNA sequencing (V1-V2) (stool sample) EDI-2, BDI, SCAS, EDE-Q	No significant differences in α-diversity between AN₀ and NW ↑ α-diversity in AN₁ than in NW β-diversity shows significant differences between AN₀ and NW, no normalizing after treatment ↑ Anaerostipes and ↓ Enterobacteriaceae, Romboutsia in AN₀ than in NW ↑ Firmicutes, Lachnospiraceae, Fusicatenibacter and ↓ Enterobacteriaceae, Romboutsia in AN₁ than in NW ↑ Ruminococcaceae, Fusicatenibacter, Lachnospiraceae, Faecalibacterium and ↓ Bacteroides in AN₁ than in AN₀
Prochazkova et al., 2021 [37]	Longitudinal	Comparison of intestinal microbiota composition and microbial metabolites in AN and NW Comparison of intestinal microbiota composition, neurohormone levels, and SCFAs at hospital admission and discharge Analysis of the composition of the fungal community	ANR₀ n = 59 BMI: 14 (13.4,15.9) Age: 23 (19,27) ANR_1, n = 52 BMI: 17.1 (15.5,18.1) NW, n = 67 BMI: 21.9 (19.9,23.7) Age: 24 (22,28.5)	Duration 51 (28.5, 62.5) days Type of treatment Weight restoration Medication maintenance (32 antidepressants, 16 antipsychotics, 32 others) Unspecified psychological treatment	Microbiological Assessment Relative abundance of bacterial and fungal taxa α-diversity (Chao-1 index, Shannon index, OTU number) and β-diversity (Bray–Curtis and Jaccard) Psychological assessment Specific symptoms of eating disorders Questionnaire addressing hyperactivity, daily habits (sleep, meals), history of stressful events, psychiatric comorbidity, antidepressant, or other medication Hidden eating disorder in healthy controls Anthropometric assessment (%) body fat Biochemical parameters SCFAs Neurohormones	16S rRNA (V3-V4) and fungal ITS2 sequencing (stool sample) EDE-Q, SCOFF BIA NMR, mass spectrometry	BMI increase predicted by several bio-psycho-social factors No significant differences in bacterial classes or genera between ANR₀, ANR₁ and NW No significant correlation between α-diversity or bacterial composition and BMI, hyperactivity, disease duration, or EDE-Q scores ↑ α-diversity (only Chao-1 index) in ANR₀ than in NW and ANR₁ ↑ β-diversity and core microbiota in ANR₀ and ANR₁ than in NW ↑ OTUs related with Alistipes finegoldi, Alistipes onderdonkii, and OTUs of Christensenellaceae, Ruminococcaceae in ANR₀ than in NW ↓ OTUs of Faecalibacterium, Agathobacter, Bacteroides, Blautia, Lachnospira in ANR₀ than in NW ↑ Megapshaera in ANR₀ than ANR₁ Changes in gut microbiota composition related to the length of hospitalization Fungal α-diversity showed no differences between groups ↑ fungal OTUs of Nakaseomyces and ↓ Mucor, Naganishia in ANR₀ than in NW Differences in predicted metabolic pathways in NW vs. ANR₀ ↓ GABA, dopamine, butyrate, and acetate levels in ANR₀ than in NW ↓ serotonine, acetate and propionate levels in ANR₁ than in NW Different OTUs showed significant associations with propionate, acetate, neurotransmitters, and biochemical or anthropometric parameters

Author, year

Study design

Objectives

Sample characteristics

Treatment

Measures

Methods

Main results

Armougom et al., 2009 [39]

Cross-sectional

Identification of specific microbial communities associated with AN, OB, or NW

AN, n = 9

BMI:12.73 ± 1.602 Age: 19–36

OB, n = 20

BMI:47.09 ± 10.66

Age: 17–72

NW, n = 20

BMI:20.68 ± 2.014

Age: 13–68

n/a

Microbiological Assessment

Bacteria copy number/ g of faeces

Real-time qPCR of microbiota species (stool sample)

↑ relative abundance of M. smithii in AN than in NW

Pfleiderer et al., 2013 [45]

Case Report

Culturomic analysis of AN stool samples

AN, n = 1

BMI: 10.4

Age: 21

n/a

Microbiological Assessment

Bacterial identification

Mass spectrometry (MALDI-TOF)

Culture Growth

Identification of 11 new bacterial species

Million et al., 2013 [41]

Cross-sectional

Comparison of faecal concentrations of Escherichia coli, M. smithii, Bifidobacterium animalis, and Lactobacillus spp in OB, OW, NW, and AN

AN, n = 15

BMI:13.5 (11.7–14.6)

Age: 27.3 ± 10.8

NW, n = 76

BMI:22.4 (20.7–23.7)

Age: 49.5 ± 18.6

OW, n = 38

BMI: 27.1 (25.9–28.6)

Age: 54.1 ± 17.8

OB, n = 134

BMI: 40.0 (36.4–46.8)

Age: 51.8 ± 14.7

n/a

Microbiological Assessment

Prevalence of each bacterial taxonomic group

Concentration (log10 copies of DNA / ml)

Real-time PCR of microbiota species (stool sample)

BMI was negatively correlated to M. smithii, E. coli, and B. animalis

BMI was positively correlated to Lactobacillus reuteri

Morita et al., 2015 [43]

Cross-sectional

Comparison of intestinal microbiota composition in NW, ANBP, and ANR

ANR, n = 14

BMI: 12.7 ± 1.5

Age: 28.1 ± 10.7

ANBP, n = 11

BMI: 13.0 ± 1.2

Age: 32.5 ± 9.4

NW, n = 21

BMI: 20.5 ± 2.1

Age: 31.5 ± 7.4

n/a

Microbiological Assessment

Prevalence of each bacterial taxonomic group

log10 cells / g of faeces

Biochemical parameters

SCFAs

Yakult Intestinal Flora-SCAN (YIF-SCAN®): Reverse transcription-qPCR of microbiota species (stool sample) based on 16S and 23S rRNA analysis

Biochemical analysis of blood samples

High-performance liquid chromatography (HPLC) of stool samples

↓ bacterial count of Streptococcus, C. coccoides, C. leptum, B. fragilis, and L. plantarum in AN than in NW

↓ C. coccoides in ANR than in NW

↓ B. fragilis in ANR and ANBP than in NW

↓ acetic and propionic acid in AN than in NW

No significant differences were found in butyrate concentrations between AN and NW

Kleiman et al., 2015 [34]

Longitudinal

Evaluation of changes to intestinal microbiota in AN patients after hospital-based weight restoration

Comparison of intestinal microbiota composition in AN and in a normal weight group

Assessment of the association between microbial composition, depression, anxiety, and eating disorder psychopathology

AN_0, n = 16

BMI: 16.2 ± 1.5

Age:28 ± 11.7

AN_1, n = 10

BMI: 17.4 ± 0.9

NW, n = 12

BMI: 21.5 ± 1.9

Age:29.8 ± 11.6

Duration

Not specified

Type of treatment

Weight restoration

Other unspecified pharmacological/psychological treatment

Microbiological Assessment

Taxa relative abundance

α-diversity (species richness, Chao-1 index) and β-diversity (UniFrac distances)

Psychological assessment

Specific psychopathological characteristics related to eating disorders and, anxious or depressive symptoms

16S rRNA sequencing (V1-V3) (stool sample)

BAI, BDI, EDE-Q

↓ genera of Coriobacteriaceae, Parabacteroidetes and ↑ genera of Ruminococcaceae in AN₁ than NW

↑ Bacilli, Coriobacteriales and ↓ Clostridiales, Clostridia, Anaerostipes, Faecalibacterium in AN₀ than NW

↓ α-diversity in AN₀ and AN₁ than NW

Significant difference in β-diversity between AN and NW that normalized after treatment

α-diversity was negatively associated to EDE-Q total scores, BDI, and subscales scores for shape and weight concern

Mack et al., 2016 [35]

Longitudinal

Comparison of intestinal microbiota composition in AN and NW

Evaluation of changes in microbiota composition in post-weight gain and/or normalisation of eating behaviour

Assessment of SCFAs profiles (pre- and post-weight gain) dietary intake, and gastrointestinal symptoms

AN_0, n = 55

BMI: 15.3 ± 1.4

Age: 23.8 ± 6.8

AN_1, n = 44

BMI: 17.7 ± 1.4

NW, n = 55

BMI: 21.6 ± 2.0

Age: 23.7 ± 6,7

Duration

3,5 ± 1,7 months

Type of treatment

Weight restoration

Normalized eating habits

Other unspecified pharmacological/psychological treatment

Microbiological Assessment

Relative abundance of bacterial taxa

Prevalence of bacterial taxa

α-diversity (Species richness, Chao-1 index, Shannon index) and β-diversity (unweighted UniFrac distance, Bray–Curtis dissimilarity)

SCFAs

Gastrointestinal symptoms

16S rRNA sequencing (V4) (stool sample)

Gas chromatography

Gastro-questionnaire

↓ Bacteroidetes to Firmicutes ratio in AN₀ than NW, further decreasing after treatment

↑ Actinobacteria in AN₀ than in NW

↑ Verrucomicrobia in AN₀ than in NW, normalizing after treatment

AN₀ shows ↑ relative abundance of M. smithii (but ↓ prevalence), mucin degrading bacteria (Anaerostipes, Anaerotruncus, Akkermansia), Clostridium cluster I, XI, XVIII, and Bifidobacterium

No significant differences in α-diversity between AN and NW

Significantly lower β-diversity in the same AN individual at different times (AN₀-AN₁) than in different subjects in the respective groups

↑ valerate, iso-butyrate and, BFCAs concentrations in AN₀ and AN₁ as compred to NW

Mörkl et al., 2017 [44]

Cross-sectional

Comparison of intestinal microbiota in AN, AT, NW, OW, and OB groups

AN, n = 18

BMI: 15.3 ± 1.3

Age: 22.44 ± 3.20

AT, n = 20

BMI:22.14 ± 1.76

Age: 22.15 ± 3.86

NW, n = 26

BMI:21.89 ± 1.73

Age: 24.93 ± 3.75

OW, n = 22

BMI:26.99 ± 1.13

Age: 25.32 ± 3.98

OB, n = 20

BMI:34.55 ± 4.43

Age: 26.9 ± 6.10

n/a

Microbiological Assessment

Relative abundance of bacterial taxa

α-diversity (species richness, Chao-1 index, Shannon index) and β-diversity (weighted and unweighted UniFrac distance)

Psychological assessment

Depressive symptoms

Anthropometric assessment

(%) body fat

Body fat distribution

Biochemical Parameters

16S rRNA sequencing (V1-V2) (stool sample)

BDI, HAMD

BIA, ultrasound measurements

↑ Coriobacteriaceae in AN than in NW

No significant differences in α- and β-diversity between AN and NW, but significant differences between AN and AT

α-diversity was negatively correlated to BDI scores when all groups were included in the analysis

Borgo et al., 2017 [40]

Cross-sectional

Evaluation of the relationship between intestinal microbiota composition, nutritional status, and psychological characteristics in ANR

ANR, n = 15

BMI:13.82 ± 1.80

Age: 25.6 ± 7.97

NW, n = 15

BMI:22.06 ± 2.55

Age: 24.4 ± 5.79

n/a

Microbiological Assessment

Relative abundance of bacterial taxa

Prevalence of M. smithii

M. smithii copy number

α-diversity and β-diversity (OTU-based methods)

Psychological assessment

General psychopathology, typical cognitive and behavioural characteristics of eating disorders, and anxious or depressive symptoms

SCFAs

16S rRNA sequencing (V3-V4) (stool sample)

Real-time qPCR for M. smithii

SCL-90, EDI-2, STAI-Y, BDI-II

Gas chromatography

↓ Firmicutes, Ruminococcus, Roseburia, Clostridium, and ↑ Proteobacteria, Enterobacteriaceae in AN than NW

↑ prevalence and absolute abundance of M. smithii in AN than NW

No significant differences in α- and β-diversity between AN and NW

BMI was negatively associated to obsession-compulsion score (SCL-90), state anxiety score (STAI-Y), trait anxiety score (STAI-Y), and BDI total score

Clostridium spp. was negatively correlated with BDI score

↓ butyrate and propionate levels in AN than in NW

No differences in acetate, iso-valerate and iso-butyrate levels between AN and NW

Butyrate was negatively correlated to depression and anxiety scores

Kleiman et al., 2017 [47]

Case series

Characterization of daily changes in intestinal microbiota composition and diversity in three acute AN patients during hospital-based renourishment

AN_0, n = 3

BMI: 15.6, 17.6,13.7

Age: 25,29,16

AN_1,

BMI: 20.2, 21.1, 15.4

Duration

Between 34 and 73 days

Type of treatment

Weight restoration

Other unspecified pharmacological/psychological treatment

Microbiological Assessment

Relative abundance of bacterial taxa

α-diversity (Shannon index) and β-diversity (unweighted UniFrac distance)

Biochemical parameters

16S rRNA sequencing (V4) (stool sample)

Patient-specific changes in intestinal microbiota composition and diversity during renourishment

Prochazkova et al., 2019 [46]

Case Report

Assessment of intestinal microbiota composition and microbial metabolites post FMT in a woman with AN

Evaluation of the effects of FMT on the patient’s psychiatric conditions

AN, n = 1

BMI: 12.36

Age: 37

Healthy donor, n = 1

Age: 67

Type of treatment

FMT

Microbiological Assessment

Log10 copies 16S rRNA/40 ng gDNA

Relative abundance of bacterial and fungal taxa

α-diversity (species richness, Chao-1 index, Shannon index) and β-diversity (non-metric multidimensional scaling)

Psychological assessment

Psychiatric symptoms, family dynamics, and specific eating disorder symptoms

SCFAs

Metabolites of the tryptophan pathway in the intestine

Intestinal permeability

I-FABP levels

qPCR

16S rRNA sequencing (V4) and ITS fungal region sequencing (stool sample)

EDE-Q, BAI, BDI II

NMR, Mass spectrometry

Eating pattern, mood, and gastrointestinal complaints remain unchanged after FMT

↑ absolute abundance of A. muciniphila and M. smithii at 12 months post-FMT

Significant changes in bacterial and fungal composition post-FMT

↑ α-diversity and SCFAs level post-FMT

↓ faecal serotonin level and intestinal permeability post-FMT

Monteleone et al., 2021a [36]

Longitudinal

Evaluation of intestinal microbiota composition in women with AN during weight restoration

Evaluation of metabolomic changes in AN pre and post-weight restoration

AN_0, n = 21

BMI: 14.6 ± 1.3

Age: 21.7 ± 4.2

AN_1, n = 20

BMI: 20.5 ± 0.7

NW, n = 20

BMI: 20.3 ± 1.4

Age: 23.0 ± 3.3

NW_1, n = 16

Duration

5 months

Type of treatment

Nutritional Rehabilitation

Enhanced Cognitive Behaviour Therapy

9 patients received SSRI

Microbiological Assessment

Relative abundance of bacterial taxa

α-diversity (Chao-1 index, Fisher index), and β-diversity (non-metric multidimensional scaling)

Psychological assessment

General psychopathology, and specific symptoms of eating disorders

Metabolomic Analysis

16S rRNA sequencing (V4) (stool sample)

EDE-Q, BSI, and SCL-90

gas chromatography–mass spectrometry system

↓ α-diversity in AN₀ than in NW, normalizing in AN₁

No significant difference in β-diversity between AN and NW

↑ Actinobacteria, Coprococcus, Weissella and ↓ Bacteroidetes, Firmicutes, Coriobacteriales, Oxalobacteriaceae, Parabacteroides in AN₀ than NW

↑ Firmicutes, Bacteroidetes, Leuconostocaceae and ↓ Actinobacteria, Coriobacteriales, Catabacteriaceae, Parabacteroidetes, Collinsella, Catabacter in AN₁ than NW

Different bacterial taxa were significantly correlated to BMI, EDE-Q total score, and BSI total scores

Monteleone et al., 2021b [42]

Cross-

sectional

Comparison of intestinal microbiota composition in NW, ANR, and ANBP

Evaluation of the metabolomic profile and its associations with the intestinal microbiota in individuals with ANR and ANBP

ANR, n = 17

BMI: 15.0 ± 1.8

Age: 20.5 ± 3.1

ANBP, n = 6

BMI: 14.7 ± 1.5

Age: 25.2 ± 5.2

NW, n = 20

BMI: 20.3 ± 1.4

Age: 23.0 ± 3.3

n/a

Microbiological Assessment

Relative abundance of bacterial taxa

α-diversity (Chao-1 index) and β-diversity (non-metric multidimensional scaling)

Metabolomic Analysis

16S rRNA (V4) sequencing (stool sample)

Gas chromatography–mass spectrometry system

↑ Verrucomicrobia, and ↓ C. coccoides, B. fragilis in ANR as compared to NW

↓ Odoribacter, Eubacteriaceae in ANBP than NW

↓ Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales and ↑ Haemophilus, Pasteurellaceae, Pasteurellales in ANR than ANBP

↓ α-diversity in AN than NW

No significant difference in β-diversity between AN and NW

Significant differences in metabolomic levels between ANBP, ANR, and NW

Schulz et al., 2021 [38]

Longitudinal

Comparison of intestinal microbiota composition and diversity in adolescents with AN and age-matched NW individuals

Evaluation of intestinal microbiota composition and diversity in AN adolescents during pre and post-weight recovery

AN_0, n = 19

BMI:15.76 ± 2.03

Age: 15.77 ± 1.94

AN_1, n = 19

BMI: 18.8 ± 0.87

NW, n = 20

BMI:20.31 ± 2.35

Age: 16.35 ± 1.11

Duration

4.05 ± 1.39 months

Type of treatment

Weight restoration

Individual and group psychotherapy, parent psychoeducation and training, occupational-, music- and physical therapy

Microbiological Assessment

Relative abundance of bacterial taxa

α-diversity (Species richness, Chao-1 index, Shannon index) and β-diversity (Bray–Curtis and Jaccard)

Psychological assessment

Specific characteristics of eating disorders, and anxious or depressive symptoms

16S rRNA sequencing (V1-V2) (stool sample)

EDI-2, BDI, SCAS, EDE-Q

No significant differences in α-diversity between AN₀ and NW

↑ α-diversity in AN₁ than in NW

β-diversity shows significant differences between AN₀ and NW, no normalizing after treatment

↑ Anaerostipes and ↓ Enterobacteriaceae, Romboutsia in AN₀ than in NW

↑ Firmicutes, Lachnospiraceae, Fusicatenibacter and ↓ Enterobacteriaceae, Romboutsia in AN₁ than in NW

↑ Ruminococcaceae, Fusicatenibacter, Lachnospiraceae, Faecalibacterium and ↓ Bacteroides in AN₁ than in AN₀

Prochazkova et al., 2021 [37]

Longitudinal

Comparison of intestinal microbiota composition and microbial metabolites in AN and NW

Comparison of intestinal microbiota composition, neurohormone levels, and SCFAs at hospital admission and discharge

Analysis of the composition of the fungal community

ANR₀ n = 59

BMI: 14 (13.4,15.9)

Age: 23 (19,27)

ANR_1, n = 52

BMI: 17.1 (15.5,18.1)

NW, n = 67

BMI: 21.9 (19.9,23.7)

Age: 24 (22,28.5)

Duration

51 (28.5, 62.5) days

Type of treatment

Weight restoration

Medication maintenance (32 antidepressants, 16 antipsychotics, 32 others)

Unspecified psychological treatment

Microbiological Assessment

Relative abundance of bacterial and fungal taxa

α-diversity (Chao-1 index, Shannon index, OTU number) and β-diversity (Bray–Curtis and Jaccard)

Psychological assessment

Specific symptoms of eating disorders

Questionnaire addressing hyperactivity, daily habits (sleep, meals), history of stressful events, psychiatric comorbidity, antidepressant, or other medication

Hidden eating disorder in healthy controls

Anthropometric assessment

(%) body fat

Biochemical parameters

SCFAs

Neurohormones

16S rRNA (V3-V4) and fungal ITS2 sequencing (stool sample)

EDE-Q, SCOFF

BIA

NMR, mass spectrometry

BMI increase predicted by several bio-psycho-social factors

No significant differences in bacterial classes or genera between ANR₀, ANR₁ and NW

No significant correlation between α-diversity or bacterial composition and BMI, hyperactivity, disease duration, or EDE-Q scores

↑ α-diversity (only Chao-1 index) in ANR₀ than in NW and ANR₁

↑ β-diversity and core microbiota in ANR₀ and ANR₁ than in NW

↑ OTUs related with Alistipes finegoldi, Alistipes onderdonkii, and OTUs of Christensenellaceae, Ruminococcaceae in ANR₀ than in NW

↓ OTUs of Faecalibacterium, Agathobacter, Bacteroides, Blautia, Lachnospira in ANR₀ than in NW

↑ Megapshaera in ANR₀ than ANR₁

Changes in gut microbiota composition related to the length of hospitalization

Fungal α-diversity showed no differences between groups

↑ fungal OTUs of Nakaseomyces and ↓ Mucor, Naganishia in ANR₀ than in NW

Differences in predicted metabolic pathways in NW vs. ANR₀

↓ GABA, dopamine, butyrate, and acetate levels in ANR₀ than in NW

↓ serotonine, acetate and propionate levels in ANR₁ than in NW

Different OTUs showed significant associations with propionate, acetate, neurotransmitters, and biochemical or anthropometric parameters

Age and BMI measurements are reported, when required, as mean ± SD. AN (participants with anorexia nervosa), ANR (participants with restrictive AN subtype), ANBP (participants with binge-eating AN subtype), AN₀ (pre-treatment AN), AN₁ (post-treatment AN), OB (obesity control group), OW (overweight control group), NW (normal weight control group), SCFAs (short chain fatty acids), qPCR (quantitative polymerase chain reaction), BIA (bioimpedance), OTU (operative taxonomic unit), FMT (faecal microbiota transplantation), NMR (nuclear magnetic resonance), n/a (not applicable)

↓ Significant decrease

↑ Significant increase