Current Perspectives on Gut Microbiome Dysbiosis and Depression

Capuco, Alexander; Urits, Ivan; Hasoon, Jamal; Chun, Rebecca; Gerald, Brittany; Wang, Jason K.; Kassem, Hisham; Ngo, Anh L.; Abd‐Elsayed, Alaa; Simopoulos, Thomas; Kaye, Alan D.; Viswanath, Omar

doi:10.1007/s12325-020-01272-7

Cited by 96 publications

(58 citation statements)

References 48 publications

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“…Many gut-brain axis studies emphasize the effects elicited by the microbiota on the brain and body, particularly with regard to mood and behavior. 6,18,30,[93][94][95] However, communication along the gut-brain axis is bidirectional, 4 so it is important to characterize the relationship from the perspectives of both bacteria (gut) and host (brain). There is already evidence of diurnal variation in the gut microbiota, 69,70,[96][97][98][99] evidence that gut microbes influence host circadian clock functions, 34,96,97,[100][101][102][103] and evidence that the circadian rhythms of the microbiota are regulated by the rhythms of the host.…”

Section: Discussionmentioning

confidence: 99%

“…Communication along the gut‐brain axis is complex, and although it is established that endocrine, neural, metabolic, and immune factors are all involved, 32,91,92 there is still much unknown regarding both the network that connects these factors and the roles of individual tissues/factors. Many gut‐brain axis studies emphasize the effects elicited by the microbiota on the brain and body, particularly with regard to mood and behavior 6,18,30,93‐95 . However, communication along the gut‐brain axis is bidirectional, 4 so it is important to characterize the relationship from the perspectives of both bacteria (gut) and host (brain).…”

Section: Discussionmentioning

confidence: 99%

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A novel role for the pineal gland: Regulating seasonal shifts in the gut microbiota of Siberian hamsters

Shor

Brown

Freeman

2020

Journal of Pineal Research

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The gut microbiota plays a significant role in a variety of host behavioral and physiological processes. The mechanisms by which the gut microbiota and the host communicate are not fully resolved but include both humoral and direct neural signals. The composition of the microbiota is affected by internal (host) factors and external (environmental) factors. One such signal is photoperiod, which is represented endogenously by nocturnal pineal melatonin (MEL) secretion. Removal of the MEL signal via pinealectomy abolishes many seasonal responses to photoperiod. In Siberian hamsters (Phodopus sungorus), MEL drives robust seasonal shifts in physiology and behavior, such as immunity, stress, body mass, and aggression. While the profile of the gut microbiota also changes by season, it is unclear whether these changes are driven by pineal signals. We hypothesized that the pineal gland mediates seasonal alterations in the composition of the gut microbiota. To test this, we placed pinealectomized and intact hamsters into long or short photoperiods for 8 weeks, collected weekly fecal samples, and measured weekly food intake, testis volume, and body mass. We determined microbiota composition using 16S rRNA sequencing (Illumina MiSeq). We found significant effects of treatment and time on the abundances of numerous bacterial genera. We also found significant associations between individual OTU abundances and body mass, testis mass, and food intake, respectively. Finally, results indicate a relationship between overall community structure, and body and testis masses. These results firmly establish a role for the pineal gland in mediating seasonal alterations in the gut microbiota. Further, these results identify a novel neuroendocrine pathway by which a host regulates seasonal shifts in gut community composition, and indicates a relationship between seasonal changes in the gut microbiota and seasonal physiological adjustments.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A novel role for the pineal gland: Regulating seasonal shifts in the gut microbiota of Siberian hamsters

Shor

Brown

Freeman

2020

Journal of Pineal Research

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“…The gut microbes secrete several important substances such as GABA, histamine, 5-HT, and DA, which contribute to neuroactive and immune regulation (Barrett et al, 2012 ; Lyte, 2013 ), and also produce toxic substances to the brain, such as ammonia and others (Galland, 2014 ). In addition, the microbiome–gut–brain axis can be affected by microbiota via immunological, neuroendocrine, and direct neural mechanisms (Logsdon et al, 2018 ), which insulted the brain to cause memory impairment, anxiety, and other cognitive dysfunctions (Gareau et al, 2011 ; Galland, 2014 ; Johnson and Foster, 2018 ) and resulted in several diseases, such as anxiety and depression (Lach et al, 2018 ; Capuco et al, 2020 ), neurodegenerative diseases, and drug-resistant epilepsy (Braakman and van Ingen, 2018 ).…”

Section: Links Between Gut and Brain Via Microbiommentioning

confidence: 99%

Target Dysbiosis of Gut Microbes as a Future Therapeutic Manipulation in Alzheimer’s Disease

Zhu

Chu

et al. 2020

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is commonly an age-associated dementia with neurodegeneration. The pathogenesis of AD is complex and still remains unclear. The inflammation, amyloid β (Aβ), and neurofibrillary tangles as well misfolded tau protein in the brain may contribute to the occurrence and development of AD. Compared with tau protein, Aβ is less toxic. So far, all efforts made in the treatments of AD with targeting these pathogenic factors were unsuccessful over the past decades. Recently, many studies demonstrated that changes of the intestinal environment and gut microbiota via gut–brain axis pathway can cause neurological disorders, such as AD, which may be involved in the pathogenesis of AD. Thus, remodeling the gut microbiota by various ways to maintain their balance might be a novel therapeutic strategy for AD. In the review article, we analyzed the characteristics of gut microbiota and its dysbiosis in AD and its animal models and investigated the possibility of targeting the gut microbiota in the treatment of the patients with AD in the future.

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“…Accumulating evidence suggests that the brain-gutmicrobiota axis plays an important role in the pathogenesis of depression, as the composition of gut microbiota in patients with depression is altered compared with healthy control subjects [27][28][29] . Preclinical studies showed that abnormal composition of gut microbiota might contribute to the depression-like behaviors detected in rodents [30][31][32][33][34][35][36][37][38][39] . Interestingly, it is suggested that the communication between the brain and the endogenous and exogenous microorganisms in the gut is modulated by the vagus nerve system [40][41][42][43][44][45][46] .…”

Section: Introductionmentioning

confidence: 99%

A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration

et al. 2020

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The vagus nerve plays a role in the cross talk between the brain and gut microbiota, which could be involved in depression. The subdiaphragmatic vagus nerve serves as a major modulatory pathway between the brain and gut microbiota. Here, we investigated the effects of subdiaphragmatic vagotomy (SDV) on the depression-like phenotype and the abnormal composition of gut microbiota in mice after lipopolysaccharide (LPS) administration. LPS caused a depression-like phenotype, inflammation, increase in spleen weight, and downregulation of synaptic proteins in the medial prefrontal cortex (mPFC) in the sham-operated mice. In contrast, LPS did not produce a depression-like phenotype and downregulated synaptic proteins in the mPFC after SDV. The spleen weight and plasma levels of proinflammatory cytokines in the SDV + LPS group were lower than those of the sham + LPS group. Interestingly, there were positive correlations between the plasma levels of pro-inflammatory cytokines and spleen weight, suggesting a relationship between inflammatory events and spleen weight. Furthermore, LPS led to significant alterations in gut microbiota diversity in sham-operated mice, but not SDV-operated mice. In an unweighted UniFrac PCoA, the dots representing the sham + LPS group were located far away from the dots representing the other three groups. Our results suggest that LPS produces a depression-like phenotype, increases spleen weight, triggers inflammation, downregulates synaptic proteins in the mPFC, and leads to abnormal composition of gut microbiota via the subdiaphragmatic vagus nerve. It is likely that the vagus nerve plays a crucial role in the brain-gut-microbiota axis.

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Current Perspectives on Gut Microbiome Dysbiosis and Depression

Cited by 96 publications

References 48 publications

A novel role for the pineal gland: Regulating seasonal shifts in the gut microbiota of Siberian hamsters

A novel role for the pineal gland: Regulating seasonal shifts in the gut microbiota of Siberian hamsters

Target Dysbiosis of Gut Microbes as a Future Therapeutic Manipulation in Alzheimer’s Disease

A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration

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