Gut microbiota and brain alterations in a translational anorexia nervosa rat model

Trinh, Stefanie; Kogel, Vanessa; Voelz, Clara; Schlösser, Anna; Schwenzer, Constanze; Kabbert, Johanna; Heussen, N.; Clavel, Thomas; Herpertz‐Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

doi:10.1016/j.jpsychires.2020.12.030

Cited by 25 publications

(22 citation statements)

References 45 publications

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“…Two of these studies employed germ-free mouse models ( Mus musculus ), C57BL/6 [ 65 ], and BALB/c [ 66 ]. One study employed C57Bl/6JRj mice [ 64 ], while another used Wistar rats [ 67 ]. There were also differences regarding the sex of the animals i.e., two studies employed females [ 66 , 67 ], one study used males [ 64 ], and another mixed groups [ 65 ].…”

Section: Resultsmentioning

confidence: 99%

Anorexia nervosa and microbiota: systematic review and critical appraisal

Garcia

Gutiérrez

2023

Eat Weight Disord

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Purpose Recent studies have reported a gut microbiota imbalance or dysbiosis associated with anorexia nervosa (AN), which has prompted an appraisal of its aetiological role, and the reformulation of AN as a metabo-psychiatric disorder. Thus, the aim of this paper was to critically review the current scientific findings regarding the role of microbiota in anorexia nervosa. Methods A systematic study of peer-reviewed literature published in four databases between 2009 and 2022 was conducted according to PRISMA guidelines. Both human and animal studies were included. Results A total of 18 studies were included. In animal models, both the preclinical and clinical findings were inconsistent regarding microbiota composition, faecal metabolite concentrations, and the effects of human faecal microbiota transplants. Conclusion The methodological limitations, lack of standardisation, and conceptual ambiguity hinder the analysis of microbiota as a key explanatory factor for AN. Level of evidence Level I, systematic review.

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Section: Resultsmentioning

confidence: 99%

Anorexia nervosa and microbiota: systematic review and critical appraisal

Garcia

Gutiérrez

2023

Eat Weight Disord

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“…The gut microbiota of the ABA model was also investigated [ 157 ], pointing out a positive correlation between serum leptin levels and quantity of Bifidobacterium and Lactobacillus , and a negative correlation between the same hormone and the number of Clostridium, Bacteroides and Prevotella . Ghrelin correlation was the opposite of that found for leptin [ 158 ].…”

Section: Resultsmentioning

confidence: 99%

Activity-based anorexia animal model: a review of the main neurobiological findings

et al. 2021

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Background The genesis of anorexia nervosa (AN), a severe eating disorder with a pervasive effect on many brain functions such as attention, emotions, reward processing, cognition and motor control, has not yet been understood. Since our current knowledge of the genetic aspects of AN is limited, we are left with a large and diversified number of biological, psychological and environmental risk factors, called into question as potential triggers of this chronic condition with a high relapse rate. One of the most valid and used animal models for AN is the activity-based anorexia (ABA), which recapitulates important features of the human condition. This model is generated from naïve rodents by a self-motivated caloric restriction, where a fixed schedule food delivery induces spontaneous increased physical activity. Aim In this review, we sought to provide a summary of the experimental research conducted using the ABA model in the pursuit of potential neurobiological mechanism(s) underlying AN. Method The experimental work presented here includes evidence for neuroanatomical and neurophysiological changes in several brain regions as well as for the dysregulation of specific neurochemical synaptic and neurohormonal pathways. Results The most likely hypothesis for the mechanism behind the development of the ABA phenotype relates to an imbalance of the neural circuitry that mediates reward processing. Evidence collected here suggests that ABA animals show a large set of alterations, involving regions whose functions extend way beyond the control of reward mechanisms and eating habits. Hence, we cannot exclude a primary role of these alterations from a mechanistic theory of ABA induction. Conclusions These findings are not sufficient to solve such a major enigma in neuroscience, still they could be used to design ad hoc further experimental investigation. The prospect is that, since treatment of AN is still challenging, the ABA model could be more effectively used to shed light on the complex AN neurobiological framework, thus supporting the future development of therapeutic strategies but also the identification of biomarkers and diagnostic tools. Plain English summary Anorexia Nervosa (AN) is a severe eating disorder with a dramatic effect on many functions of our brain, such as attention, emotions, cognition and motion control. Since our current knowledge of the genetic aspects behind the development of AN is still limited, many biological, psychological and environmental factors must be taken into account as potential triggers of this condition. One of the most valid animal models for studying AN is the activity-based anorexia (ABA). In this model, rodents spontaneously limit food intake and start performing increased physical activity on a running wheel, a result of the imposition of a fixed time schedule for food delivery. In this review, we provide a detailed summary of the experimental research conducted using the ABA model, which includes extended evidence for changes in the anatomy and function of the brain of ABA rodents. The hope is that such integrated view will support the design of future experiments that will shed light on the complex brain mechanisms behind AN. Such advanced knowledge is crucial to find new, effective strategies for both the early diagnosis of AN and for its treatment.

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“…Similar to phenomena in human AN weight loss, hyperactivity, amenorrhoea, hormonal disturbances, learning deficits and brain volume loss have been shown (Frintrop, Trinh, et al., 2018 ). Recently, intestinal dysbiosis was also confirmed in the ABA animal model, which was associated with the described brain volume and astrocyte‐marker alterations (Trinh et al., 2021 ).…”

Section: Introductionmentioning

confidence: 87%

The effects of probiotics administration on the gut microbiome in adolescents with anorexia nervosa—A study protocol for a longitudinal, double‐blind, randomized, placebo‐controlled trial

Gröbner

Zeiler

Fischmeister

et al. 2021

Euro Eating Disorders Rev

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Objective Knowledge on gut–brain interaction might help to develop new therapies for patients with anorexia nervosa (AN), as severe starvation‐induced changes of the microbiome (MI) do not normalise with weight gain. We examine the effects of probiotics supplementation on the gut MI in patients with AN. Method This is a study protocol for a two‐centre double‐blind randomized‐controlled trial comparing the clinical efficacy of multistrain probiotic administration in addition to treatment‐as‐usual compared to placebo in 60 patients with AN (13–19 years). Moreover, 60 sex‐ and age‐matched healthy controls are included in order to record development‐related changes. Assessments are conducted at baseline, discharge, 6 and 12 months after baseline. Assessments include measures of body mass index, psychopathology (including eating‐disorder‐related psychopathology, depression and anxiety), neuropsychological measures, serum and stool analyses. We hypothesise that probiotic administration will have positive effects on the gut microbiota and the treatment of AN by improvement of weight gain, gastrointestinal complaints and psychopathology, and reduction of inflammatory processes compared to placebo. Conclusions If probiotics could help to normalise the MI composition, reduce inflammation and gastrointestinal discomfort and increase body weight, its administration would be a readily applicable additional component of multi‐modal AN treatment.

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Gut microbiota and brain alterations in a translational anorexia nervosa rat model

Cited by 25 publications

References 45 publications

Anorexia nervosa and microbiota: systematic review and critical appraisal

Anorexia nervosa and microbiota: systematic review and critical appraisal

Activity-based anorexia animal model: a review of the main neurobiological findings

The effects of probiotics administration on the gut microbiome in adolescents with anorexia nervosa—A study protocol for a longitudinal, double‐blind, randomized, placebo‐controlled trial

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