Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response

Chen, Yi-huan; Bai, Jie; Wu, Di; Yu, Shou-fen; Qiang, Xiao-ling; Bai, Hua; Wang, Huaning; Peng, Zhengwu

doi:10.1016/j.jad.2019.08.014

Cited by 139 publications

(89 citation statements)

References 66 publications

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“…Previous studies have demonstrated the complex interaction between gut microbiota and the CNS; this is what is known as the MGB axis (Wang and Wang, 2016 ). Animal experiments support that absence or change in gut microbiota affects the HPA axis answering to stress, anxiety, and relevant behavior (Koopman and El Aidy, 2017 ; Lach et al, 2018 ; Chen et al, 2019 ). In addition, the rodents infected with intestinal pathogens showed anxiety-like behaviors, which can be partly explained by the activation of vagal afferents (Klarer et al, 2014 ).…”

Section: Discussionmentioning

confidence: 98%

Long-Term Exposure to Ceftriaxone Sodium Induces Alteration of Gut Microbiota Accompanied by Abnormal Behaviors in Mice

Zhao

Wang

et al. 2020

Front. Cell. Infect. Microbiol.

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Background: Growing evidence points out that a disturbance of gut microbiota may also disturb the gut-brain communication. However, it is not clear to what extent the alteration of microbiota composition can modulate brain function, affecting host behaviors. Here, we investigated the effects of gut microbiota depletion on emotional behaviors. Methods: Mice in the experimental group were orally administered ceftriaxone sodium solution (250 mg/ml, 0.2 ml/d) for 11 weeks. The open-field test and tail-suspension test were employed for the neurobehavioral assessment of the mice. Fecal samples were collected for 16s rDNA sequencing. The serum levels of cytokines and corticosterone were quantified using enzyme-linked immunosorbent assays. The immunohistochemistry method was used for the detection of brain-derived neurotrophic factor (BDNF) and c-Fos protein. Results: The gut microbiota for antibiotic-treated mice showed lower richness and diversity compared with normal controls. This effect was accompanied by increased anxiety-like, depression-like, and aggressive behaviors. We found these changes to be possibly associated with a dysregulation of the immune system, abnormal activity of the hypothalamic-pituitary-adrenal axis, and an alteration of neurochemistry. Conclusions: The findings demonstrate the indispensable role of microbiota in the gut-brain communication and suggest that the absence of conventional gut microbiota could affect the nervous system, influencing brain function.

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Section: Discussionmentioning

confidence: 98%

Long-Term Exposure to Ceftriaxone Sodium Induces Alteration of Gut Microbiota Accompanied by Abnormal Behaviors in Mice

Zhao

Wang

et al. 2020

Front. Cell. Infect. Microbiol.

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“…At the phyla level, Ascomycota and Basidiomycota dominated the fecal fungi, while only Zygomycota showed a significant difference between D‐IBS and HC Basidiomycota / Ascomycota ratio, which did not change in D‐IBS in our study was used as a fungal dysbiosis index in IBD 12 . Although previous studies suggested both anxiety 38 and depression 39 could alter composition of gut microbiota, gut fungal profiles did not differ between IBS patients with and without anxiety or depression in our study, indicating mental state may not impact gut fungi of D‐IBS patients.…”

Section: Discussionmentioning

confidence: 47%

“…AUC, area under the curve; CV Error, the cross-validation error; POD, probability of disease; ROC, receiver operating characteristic Basidiomycota/Ascomycota ratio, which did not change in D-IBS in our study was used as a fungal dysbiosis index in IBD 12. Although previous studies suggested both anxiety38 and depression 39 could alter composition of gut microbiota, gut fungal profiles did not differ between IBS patients with and without anxiety or depression in our study, indicating mental state may not impact gut fungi of D-IBS patients. We identified specific fungal genera including Mycosphaerella, Aspergillus, Sporidiobolus, and Pandora which may potentially discriminate D-IBS from HC Mycosphaerella could produce and release mycousnine, a selective and low-toxic immunosuppressant, which involves in immune regulation and host defense.…”

mentioning

confidence: 66%

Gut fungal dysbiosis and altered bacterial‐fungal interaction in patients with diarrhea‐predominant irritable bowel syndrome: An explorative study

Hong

Liu

Yang

et al. 2020

Neurogastroenterology Motil

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Background: Little is known about intestinal fungi in IBS patients whose gut bacteria have been investigated a lot. In order to explore causal relationship between IBS and gut mycobiome, and use gut fungi to diagnose or even treat IBS, further characterization of it in IBS is required. Methods: Fifty-five diarrhea-predominant IBS (D-IBS) patients fulfilling Rome III criteria, and 16 healthy controls (HC) were recruited. Fresh fecal samples were collected and used for 16s rRNA and ITS2 high-throughput sequencing. Diversity and composition of gut bacteria and fungi, as well as bacterial-fungal interactions in D-IBS patients, were characterized. Specific fungal taxa differentiating D-IBS from HC were recognized by LEfSe and RandomForest methods, and their association with clinical symptoms was assessed by Spearman's correlation. Results: Diarrhea-predominant irritable bowel syndrome patients showed abnormal (IBS-dysbiosis) or normal (HC-like IBS) fecal bacterial structure and diversity compared with healthy controls. However, fecal fungal signatures differed absolutely between D-IBS and HC, which indicated a more susceptible alteration of gut fungi than bacteria in D-IBS. Fecal fungi showed significant correlations with IBS symptoms, especially Mycosphaerella, Aspergillus, Sporidiobolus, and Pandora which were identified to potentially differentiate D-IBS from HC. Moreover, compared with HC there were markedly declined bacterial-fungal interactions in D-IBS, in which Candida changed from negative to positive correlations with bacteria, and Eurotium changed from positive correlations to irrelevance, while Debaryomyces gained negative correlations with bacteria. Conclusions: Gut fungal dysbiosis and altered bacterial-fungal interactions were present in patients with D-IBS, and gut fungi could be used to diagnose D-IBS.

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“…Our correlation analysis showed that there was a positive correlation between white matter integrity and the relative abundance of Holdemania and Eubacterium. These bacteria are both known to be changed in abundances in other disorders: Holdemania is increased in individuals with MDD [67][68][69], and Eubacterium is decreased in children with ASD [70]. However, to our knowledge, this is the first study that found significant correlations between these bacteria and brain structural and functional changes.…”

Section: Discussionmentioning

confidence: 78%

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice

Tengeler¹,

Dam

Wiesmann³

et al. 2020

Microbiome

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Background: The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging (MRI), and studied mouse behavior in a behavioral test battery.Results: Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test. Conclusions: Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals' behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders.

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Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response

Cited by 139 publications

References 66 publications

Long-Term Exposure to Ceftriaxone Sodium Induces Alteration of Gut Microbiota Accompanied by Abnormal Behaviors in Mice

Long-Term Exposure to Ceftriaxone Sodium Induces Alteration of Gut Microbiota Accompanied by Abnormal Behaviors in Mice

Gut fungal dysbiosis and altered bacterial‐fungal interaction in patients with diarrhea‐predominant irritable bowel syndrome: An explorative study

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice

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