Table 5.

Main characteristics of animal studies included in the review

Author, year	Objectives	Sample characteristics	Intervention/Treatment	Measures	Methods	Main results
Hata et al., 2019 [66]	Comparison of body weight gain and behavioural characteristics between gAN and gNW	AN, n = 4 BMI: 13.7 ± 0.1 kg/m2 Age: 23.0 ± 3.4 NW, n = 4 BMI: 21.6 ± 1.2 kg/m2 Age: 25.3 ± 0.8 Animal model Female GF BALB/c mice Sample for microbiological assessment ngAN = 40 ngNW = 40 Sample for weight gain and food efficiency analysis ngAN = 35 ngNW = 37 Sample for behavioural assessment ngAN = 35 ngNW = 37 Sample for analysis of 5-HT and 5-HIIA levels ngAN = 10 ngNW = 10	Experimental intervention Transplantation of faecal microbiota from AN or NW into parental GF mice Probiotic treatment of gAN (Bacteroides vulgatus, 5 × 108 UFC/once a week)	Microbiological assessment Relative abundance of bacterial taxa Behavioural analysis time spent in the 12 peripheral subsquares for 20 min number of marbles buried motor activity (total distance travelled for 20 min) Other measures 5-HT and 5-HIAA levels in brain tissue % of body weight change Cumulative food intake Food efficiency	16S rRNA sequencing (V3-V4) (stool sample) Open-field test Marble burying test	↓ Relative abundance of Bacteroidetes and B. fragilis in AN than in NW ↓ body weight gain in gAN than in gNW ↓ food efficiency in gAN than in gNW Food efficiency was significantly correlated to Odoribacter or Sutterella gAN spent significantly more time in peripheral subsquares than gNW in an open-field test gAN buried more marbles than gNW in marble burying test ↓ 5-HT levels in gAN brainstem No significant changes in 5-HIAA levels Administration of B. vulgatus ↓ nº of buried marbles in gAN mice No significant differences in motor activity between gAN and gNW mice
Trinh et al., 2021 [67]	Analysis of alterations in faecal microbiota in rats using the modified ABA-model with control groups under different starvation and activity conditions	Animal model Female Wistar rats C, n = 12 CRW, n = 12 RBW, n = 12 ABA, n = 13	Experimental conditions CRW RBW ABA	Microbiological assessment Relative abundance of bacterial taxa α-diversity (Species richness, Shannon index) and β-diversity (UniFrac distances) Other measures Body weight (mean g/day) Running-wheel activity (mean distance (km)/ day) Food intake (mean g/day) Histological brain volume GFAP-positive cells per mm2 mRNA expression of GFAP	16S rRNA sequencing (V3-V4) (stool sample) Reverse transcription-qPCR Real time-PCR anti-GFAP antibody staining	Chronic food restriction ↑ α-diversity β-diversity in RBW and ABA groups were significantly different from those in the C and CRW groups ↓ Prevotella, ↑ Odoribacter, Lactobacillus, Akkermansia, Bifidobacterium, Ruminococcus in animals with reduced bodyweight in comparison to control rats Chronic food restriction had a significant influence on gut microbiota composition
Breton et al., 2021 [64]	Characterization of gut microbiota dysbiosis in an ABA model Correlations between the intestinal bacterial composition and the levels of neuropeptides POMC, or NPY	Animal model Male C57Bl/6JRj mice C, n = 6–8 LFA, n = 6–8 ABA, n = 6–8	Experimental conditions LFA ABA	Microbiological assessment Relative abundance of ASV α-diversity (Species richness and Shannon index) Quantification of neuropeptide expression NPY and POMC mRNA levels Other measures Body weight (mean g/day) Food intake (mean g/day) Running distance for ABA mice (mean distance (km)/ day)	16S rRNA sequencing (V5-V6) in mouse cecum qPCR quantification of mRNA levels	There are no significant differences in α-diversity between C, LFA and ABA mice ↑ relative abundance of Burkholderiales, Clostridium clúster XVIII and Lactobacillus in C than in ACL and ABA ↑ C. clocleatum in ABA and ACL than in C No significant differences in the relative abundance of Roseburia spp., A. muciniphila and M. smithii between groups Burkholderiales was positively correlated to body weight, food intake, and lean mass Lactobacillales was negatively correlated to body weight, food intake and lean mass 11 bacterial units were positively correlated to the POMC hypothalamic level 3 bacterial units were negatively correlated to NPY hypothalamic levels All bacterial units were positively correlated to body weight and food intake
Glenny et al., 2021 [65]	Evaluation of the effects AN intestinal microbiota on body composition and weight gain in gnotobiotic mice	AN0, n = 4 BMI: 13.8 ± 0.8 kg/m2 Age: 18.3 ± 0.3 AN1, n = 4 BMI: 18.0 ± 0.9 kg/m2 NW, n = 4 BMI: 22.0 ± 0.7 kg/m2 Age: 18.5 ± 0.3 Animal model Male and female GF C57BL/6 mice ngAN0 = 50 ngAN1 = 53 ngNW = 50	AN treatment Weight restoration Experimental intervention Transplantation of microbiota derived from AN0, AN1, and NW into GF mice (Thawed human stool, oral administration)	Microbiological assessment Relative abundance of bacterial taxa log10 normalized count α-diversity (Shannon index) and β-diversity (non-metric multidimensional scaling, Bray–Curtis dissimilarity) Another measures % change in body composition % change in body weight Average daily food intake (g/day)	16S rRNA sequencing (V4) (human and colonized mice stool samples) qPCR	No relationship between AN-associated intestinal microbiota and changes in body weight, fat mass, lean mass, or daily food consumption No significant differences in α- and β-diversity between gAN0 and gAN1

Age and BMI measurements are reported, when required, as mean ± SD. AN₀ (individuals with anorexia nervosa before treatment), AN₁ (individuals with anorexia nervosa after treatment), NW (normal weight control group), gAN (gnotobiotic mice reconstituted with gut microbes derived from individuals with AN), gNW (gnotobiotic mice transplanted with gut microbiota of normal weight female subjects), gAN₀ (gnotobiotic mice transplanted with gut microbiota from AN₀), gAN₁ (gnotobiotic mice transplanted with the gut microbiota from AN₁), C (control animals with ad libitum access to food, without free access to a running wheel), CRW (control animals with ad libitum access to food and free access to a running wheel), RBW (control animals with a 25% reduction in body weight), ABA (experimental group exposed to food restriction and free access to a running wheel), LFA (control group with restricted access to food and without access to a running wheel), GF (germ-free), ASV (amplicon sequence variant), HIAA (5-hydroxyindoleacetic acid), 5-HT (serotonin), POMC (pro-opiomelanocortin), NPY (neuropeptide Y), GFAP (glial fibrillary acidic protein)

↓ Significant decrease

↑ Significant increase