An integrated metagenomics and metabolomics approach implicates the microbiota-gut-brain axis in the pathogenesis of Huntington's disease

Kong, Geraldine; Ellul, Susan; Narayana, Vinod K.; Kanojia, Komal; Ha, Harvey Tran Thai; Li, Shanshan; Renoir, Thibault; Cao, Kim‐Anh Lê; Hannan, Anthony J.

doi:10.1016/j.nbd.2020.105199

Cited by 67 publications

(53 citation statements)

References 67 publications

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“…Our findings are also supported by preclinical evidences that constipation induced microbiota dysbiosis could modulate brain functions by immune, endocrine and neural pathways through the brain-gut-microbiota axis in other diseases [ 54 ]. It has been reported that constipation induced microbiota dysbiosis and damaged barrier function in the pathogenesis of depression, AD and PD [ 55 – 57 ].…”

Section: Discussionsupporting

confidence: 81%

Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice

Lin

Liu

et al. 2021

J Transl Med

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Background Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Methods Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood–brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-β, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups. Results Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood–brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-β, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota. Conclusions Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.

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Section: Discussionsupporting

confidence: 81%

Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice

Lin

Liu

et al. 2021

J Transl Med

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“…Gut microbiota is the collective name for the trillions of microorganisms living in an animal’s intestines, including more than 35,000 diversity species of known bacteria [ 113 ]. The function of gut microbiota is similar to a virtual endocrine organ, reacting to a variety of internal and external stimulations by producing various bioactivate factors to regulate food digestion, nutrient absorption, energy metabolism, immunity and antioxidative status, and hormonal and neurotransmitter release through the bidirectional communication of the microbiota–gut–brain axis [ 114 , 115 , 116 , 117 ]. A healthy gut microbiota is essential for the functions of the HPA and HPT axes [ 69 , 118 , 119 , 120 ].…”

Section: Heat Stress and Gut Microbiotamentioning

confidence: 99%

Bacillus subtilis-Based Probiotic Improves Skeletal Health and Immunity in Broiler Chickens Exposed to Heat Stress

Jiang

Yan

et al. 2021

Animals

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The elevation of ambient temperature beyond the thermoneutral zone leads to heat stress, which is a growing health and welfare issue for homeothermic animals aiming to maintain relatively constant reproducibility and survivability. Particularly, global warming over the past decades has resulted in more hot days with more intense, frequent, and long-lasting heat waves, resulting in a global surge in animals suffering from heat stress. Heat stress causes pathophysiological changes in animals, increasing stress sensitivity and immunosuppression, consequently leading to increased intestinal permeability (leaky gut) and related neuroinflammation. Probiotics, as well as prebiotics and synbiotics, have been used to prevent or reduce stress-induced negative effects on physiological and behavioral homeostasis in humans and various animals. The current data indicate dietary supplementation with a Bacillus subtilis-based probiotic has similar functions in poultry. This review highlights the recent findings on the effects of the probiotic Bacillus subtilis on skeletal health of broiler chickens exposed to heat stress. It provides insights to aid in the development of practical strategies for improving health and performance in poultry.

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“…Recent studies in HD patients and mouse models support a potential role for gut microbiota in disease progression (Kong et al, 2020, Wasser et al, 2020, Du et al, 2021, Kong et al, 2021.…”

Section: Discussionmentioning

confidence: 99%

“…Another gut microbiome analysis of a group of HDs patient's links blooming of gram-negative bacteria Bilophila species to elevated levels of inflammatory cytokines (Du et al, 2021). In transgenic mouse models of HD expressing the neurotoxic mutant HTTex1 peptide, gut dysbiosis has been linked to weight loss, motor deficit, metabolic changes and disruption in the intestinal epithelium (Kong et al, 2020, Stan et al, 2020, Kong et al, 2021. These promising studies highlight a potential role of gut microbiota in the pathogenesis of HD.…”

Section: Introductionmentioning

confidence: 99%

Gut bacteria regulate the pathogenesis of Huntington’s disease in Drosophila model

Chongtham

Yoo

Chin

et al. 2021

Preprint

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Changes in the composition of gut microbiota are implicated in the pathogenesis of several neurodegenerative disorders. Here, we investigated whether gut bacteria affect the hallmarks of Huntington's disease (HD) in transgenic Drosophila melanogaster (fruit fly) models expressing human full-length or N-terminal fragments of mutant huntingtin (HTT) protein, here referred to as HD flies. We find that elimination of commensal gut bacteria by antibiotics reduces the aggregation of amyloidogenic N-terminal fragments of HTT and delays the development of motor defects. Conversely, colonization of HD flies with Escherichia coli (E. coli), a known pathobiont of human gut, accelerates HTT aggregation, aggravates immobility and shortens life span. Similar to antibiotics, treatment of HD flies with compounds such as luteolin, a flavone, or crocin a beta-carotenoid, ameliorates disease phenotypes and promotes survival. Crocin prevents colonization of E. coli in the HD flies gut and alters the levels of commensal bacteria, which may be linked to its protective effects. The opposing effects of E. coli and crocin on HTT aggregation, motor defects and survival in transgenic Drosophila support the involvement of gut-brain networks in the pathogenesis of HD.

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An integrated metagenomics and metabolomics approach implicates the microbiota-gut-brain axis in the pathogenesis of Huntington's disease

Cited by 67 publications

References 67 publications

Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice

Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice

Bacillus subtilis-Based Probiotic Improves Skeletal Health and Immunity in Broiler Chickens Exposed to Heat Stress

Gut bacteria regulate the pathogenesis of Huntington’s disease in Drosophila model

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