Alessio Maria Monteleone1, Jacopo Troisi2, Alessio Fasano3, Riccardo Dalle Grave4, Francesca Marciello5, Gloria Serena3, Simona Calugi4, Giovanni Scala6, Giulio Corrivetti7, Giammarco Cascino5, Palmiero Monteleone8, Mario Maj1. 1. Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy. 2. Theoreo srl, Via degli Ulivi 3, 84090, Montecorvino Pugliano, SA, Italy; European Biomedical Research Institute of Salerno (EBRIS), Via S. De Renzi, 3, 84125, Salerno, SA, Italy. 3. Mucosal Immunology and Biology Research Center, Massachusetts General Hospital-Harvard Medical School, Boston, MA, USA. 4. Department of Eating and Weight Disorders, Villa Garda Hospital, Garda, Verona, Italy. 5. Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", Neuroscience Section, University of Salerno, Baronissi, SA, Italy. 6. Theoreo srl, Via degli Ulivi 3, 84090, Montecorvino Pugliano, SA, Italy. 7. European Biomedical Research Institute of Salerno (EBRIS), Via S. De Renzi, 3, 84125, Salerno, SA, Italy. 8. Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", Neuroscience Section, University of Salerno, Baronissi, SA, Italy. Electronic address: pmonteleone@unisa.it.
Abstract
BACKGROUND & AIMS: We have recently reported specific fecal metabolomic changes in acute and short-term weight restored patients with anorexia nervosa (AN). In this study we explored the association between those metabolomic changes and patients' gut microbiome composition. METHODS: The gut microbiome of AN women was sequenced in both the underweight phase (n = 21) and after short-term weight restoration (n = 16) and compared to that of 20 healthy women. According to a multi-omics approach, microbiome data were correlated with 49 relevant fecal metabolites previously characterized in our participants by an untargeted metabolomic procedure. RESULTS: Compared to healthy women, AN patients showed a decreased intra-individual bacterial richness, an increased Bacteroidetes-to-Firmicutes abundance ratio and significant changes in the relative abundances of several bacteria at phylum, class, order, family and genus levels. These changes were observed in both the underweight and weight-restored condition. Moreover, the relationships among the 49 previously selected fecal metabolites and bacteria genera showed structures of different complexity among the 3 groups. In particular, a quarter of those relationships showed a divergent direction in the acutely ill patients with respect to the weight-restored ones or normal controls. Finally, in acutely ill patients 70% of those correlations showed a negative sign suggesting a prevalent metabolites consummation by gut microbiome. CONCLUSIONS: These data confirm a profound perturbation in the gut microbiome composition of AN patients. Moreover, for the first time, they provide the evidence that in AN gut bacteria are connected with several fecal metabolites in a different way from normal controls and with divergent directions in the acute phase with respect to the weight-restored phase.
BACKGROUND & AIMS: We have recently reported specific fecal metabolomic changes in acute and short-term weight restored patients with anorexia nervosa (AN). In this study we explored the association between those metabolomic changes and patients' gut microbiome composition. METHODS: The gut microbiome of AN women was sequenced in both the underweight phase (n = 21) and after short-term weight restoration (n = 16) and compared to that of 20 healthy women. According to a multi-omics approach, microbiome data were correlated with 49 relevant fecal metabolites previously characterized in our participants by an untargeted metabolomic procedure. RESULTS: Compared to healthy women, AN patients showed a decreased intra-individual bacterial richness, an increased Bacteroidetes-to-Firmicutes abundance ratio and significant changes in the relative abundances of several bacteria at phylum, class, order, family and genus levels. These changes were observed in both the underweight and weight-restored condition. Moreover, the relationships among the 49 previously selected fecal metabolites and bacteria genera showed structures of different complexity among the 3 groups. In particular, a quarter of those relationships showed a divergent direction in the acutely ill patients with respect to the weight-restored ones or normal controls. Finally, in acutely ill patients 70% of those correlations showed a negative sign suggesting a prevalent metabolites consummation by gut microbiome. CONCLUSIONS: These data confirm a profound perturbation in the gut microbiome composition of AN patients. Moreover, for the first time, they provide the evidence that in AN gut bacteria are connected with several fecal metabolites in a different way from normal controls and with divergent directions in the acute phase with respect to the weight-restored phase.
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