Gut microbial metabolites in depression: understanding the biochemical mechanisms

Caspani, Giorgia; Kennedy, Sidney H.; Foster, Jane A.; Swann, Jonathan R.

doi:10.15698/mic2019.10.693

Cited by 205 publications

(175 citation statements)

References 233 publications

(284 reference statements)

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“…Numerous volatiles such as dimethyl disulfide, acetic acid, 2-nonanone, dimethyl trisulfide, 2-undecanone, isovaleric acid, 2-tridecanone, propanoic acid, and indole were produced by a significant number of bacterial genera (>75%) rather than by fungal genera. These compounds can be characterized as "typical bacterial VOCs, " and literature shows that they have been documented to be produced by bacterial species (Bos et al, 2013;Fincheira and Quiroz, 2018;Caspani et al, 2019). As a case study, we considered dimethyl disulfide and dimethyl trisulfide, which are byproducts derived from methionine amino acid degradation.…”

Section: Volatiles Frequency and Distribution Among Bacterial And Funmentioning

confidence: 99%

Sixty-One Volatiles Have Phylogenetic Signals Across Bacterial Domain and Fungal Kingdom

et al. 2020

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Microorganisms are diverse in their genome sequences and subsequently in their encoded metabolic pathways, which enabled them to adapt to numerous environmental conditions. They produce thousands of small molecules, many of which are volatiles in nature and play important roles in signaling in intra-and inter-species to kingdom and domain interactions, survival, or virulence. Many of these compounds have been studied, characterized, and organized in the mVOC 2.0 database. However, such dataset has not been investigated comprehensively in terms of its phylogeny to determine key volatile markers for certain taxa. It was hypothesized that some of the volatiles described in the mVOC 2.0 database could function as a phylogenetic signal since their production is conserved among certain taxa within the microbial evolutionary tree. Our meta-analysis revealed that some volatiles were produced by a large number of bacteria but not in fungal genera such as dimethyl disulfide, acetic acid, 2-nonanone, dimethyl trisulfide, 2-undecanone, isovaleric acid, 2-tridecanone, propanoic acid, and indole (common bacterial compounds). In contrast, 1-octen-3-ol, 3-octanone, and 2-pentylfuran (common fungal compounds) were produced primarily by fungal genera. Such chemical information was further confirmed by investigating genomic data of publicly available databases revealing that bacteria or fungi harbor gene families involved in these volatiles' biosynthesis. Our phylogenetic signal testing identified 61 volatiles with a significant phylogenetic signal as demonstrated by phylogenetic D statistic P-value < 0.05. Thirty-three volatiles were phylogenetically conserved in the bacterial domain (e.g., cyclocitral) compared to 17 volatiles phylogenetically conserved in the fungal kingdom (e.g., aristolochene), whereas 11 volatiles were phylogenetically conserved in genera from both bacteria and fungi (e.g., geosmin). These volatiles belong to different chemical classes such as heterocyclic compounds, long-chain fatty acids, sesquiterpenoids, and aromatics. The performed approaches serve as a starting point to investigate less explored volatiles with potential roles in signaling, antimicrobial therapy, or diagnostics.

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Section: Volatiles Frequency and Distribution Among Bacterial And Funmentioning

confidence: 99%

Sixty-One Volatiles Have Phylogenetic Signals Across Bacterial Domain and Fungal Kingdom

et al. 2020

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“…Shifts in bile acid homeostasis are associated with HCV infection (81) and chronic liver disease. Bile acid abundance and composition are also dysregulated in MDD (82). Our observation of increased primary and secondary bile acids in coinfected individuals with a lifetime history of MDD compared to coinfected individuals without a lifetime history of MDD suggests that dysregulated bile acid metabolism by gut bacteria may be a mechanism that links HIV-HCV coinfection and MDD.…”

Section: Resultsmentioning

confidence: 77%

Depression in Individuals Coinfected with HIV and HCV Is Associated with Systematic Differences in the Gut Microbiome and Metabolome

et al. 2020

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Depression is influenced by the structure, diversity, and composition of the gut microbiome. Although depression has been described previously in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) monoinfections, and to a lesser extent in HIV-HCV coinfection, research on the interplay between depression and the gut microbiome in these disease states is limited. Here, we characterized the gut microbiome using 16S rRNA amplicon sequencing of fecal samples from 373 participants who underwent a comprehensive neuropsychiatric assessment and the gut metabolome on a subset of these participants using untargeted metabolomics with liquid chromatography-mass spectrometry. We observed that the gut microbiome and metabolome were distinct between HIV-positive and -negative individuals. HCV infection had a large association with the microbiome that was not confounded by drug use. Therefore, we classified the participants by HIV and HCV infection status (HIV-monoinfected, HIV-HCV coinfected, or uninfected). The three groups significantly differed in their gut microbiome (unweighted UniFrac distances) and metabolome (Bray-Curtis distances). Coinfected individuals also had lower alpha diversity. Within each of the three groups, we evaluated lifetime major depressive disorder (MDD) and current Beck Depression Inventory-II. We found that the gut microbiome differed between depression states only in coinfected individuals. Coinfected individuals with a lifetime history of MDD were enriched in primary and secondary bile acids, as well as taxa previously identified in people with MDD. Collectively, we observe persistent signatures associated with depression only in coinfected individuals, suggesting that HCV itself, or interactions between HCV and HIV, may drive HIV-related neuropsychiatric differences. IMPORTANCE The human gut microbiome influences depression. Differences between the microbiomes of HIV-infected and uninfected individuals have been described, but it is not known whether these are due to HIV itself, or to common HIV comorbidities such as HCV coinfection. Limited research has explored the influence of the microbiome on depression within these groups. Here, we characterized the microbial community and metabolome in the stools from 373 people, noting the presence of current or lifetime depression as well as their HIV and HCV infection status. Our findings provide additional evidence that individuals with HIV have different microbiomes which are further altered by HCV coinfection. In individuals coinfected with both HIV and HCV, we identified microbes and molecules that were associated with depression. These results suggest that the interplay of HIV and HCV and the gut microbiome may contribute to the HIV-associated neuropsychiatric problems.

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“…Under a state of dysbiosis, induced through mucin changes, gut-derived molecule ratios may change, contributing to the etiology of depression (Carding et al, 2015;Morris et al, 2017). SCFAs are a group of metabolites produced by anaerobic fermentation of indigestible dietary carbohydrates and can act in the body in a multitude of ways (Caspani et al, 2019). SCFAs have been shown to inhibit histone deacetylase (HDAC), an enzyme that can change the epigenetic landscape and has been shown to increase depressive-like behaviors in mice (Gundersen and Blendy, 2009).…”

Section: Mucins and Gut Microbiome Metabolitesmentioning

confidence: 99%

“…Last, dysbiosis can alter the production of neurotransmitters in the gut (Caspani et al, 2019). This alteration in neurotransmitter availability, driven by mucosal changes, can feedback on more traditional aspects of depression.…”

Section: Mucins and Gut Microbiome Metabolitesmentioning

confidence: 99%

The Role of Gut Mucins in the Etiology of Depression

Rivet-Noor¹,

Gaultier²

2020

Front. Behav. Neurosci.

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Major depressive disorders are global health problems that affect more than 6% of the U.S. population. Despite years of research, the etiology of depression remains unclear. Historically, it was believed that depression started within the central nervous system (CNS), but alternative hypotheses have recently challenged this dogma. Indeed, experimental and clinical evidence show that the gut microbiome could be an active player in depression initiation. The composition of bacterial species in depressed patients is significantly different from control microbiomes, and the transfer of the microbiome from depressed patients is sufficient to initiate depressive symptoms in animals. Additionally, the gut microbiome is known to change in the presence of depression risk factors such as chronic stress. While there is strong evidence delineating a role for microbial dysbiosis in depression, the initiating event for this dysbiosis remains unknown. Within the gut, microbiota reside in the mucus layer, a critical gel-like barrier involved in protecting the host from unwanted pathogen interactions, as well as regulating the immune system. Though the mucus layer is often ignored in the face of dysbiosis, it represents a dynamic and important piece of host machinery that has the potential to impact a wide variety of biological processes. Here, we review evidence supporting the novel concept that stress can modify the delicate mucus-microbiome balance, initiating dysbiosis, and ultimately leading to depression.

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Gut microbial metabolites in depression: understanding the biochemical mechanisms

Cited by 205 publications

References 233 publications

Sixty-One Volatiles Have Phylogenetic Signals Across Bacterial Domain and Fungal Kingdom

Sixty-One Volatiles Have Phylogenetic Signals Across Bacterial Domain and Fungal Kingdom

Depression in Individuals Coinfected with HIV and HCV Is Associated with Systematic Differences in the Gut Microbiome and Metabolome

The Role of Gut Mucins in the Etiology of Depression

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