Microbiota modulate sympathetic neurons via a gut–brain circuit

Müller, Paul; Schneeberger, Marc; Matheis, Fanny; Wang, Putianqi; Kerner, Zachary; Ilanges, Anoj; Pellegrino, Kyle; Mármol, Josefina del; Castro, Tiago B. R.; Furuichi, Munehiro; Perkins, Matthew H.; Han, Wenfei; Rao, Arka; Pickard, Amanda J.; Cross, Justin R.; Honda, Kenya; Araújo, Ivan de; Mucida, Daniel

doi:10.1038/s41586-020-2474-7

Cited by 294 publications

(214 citation statements)

References 46 publications

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“…Another plausible factor linking ASD, PCBs and the PNS is the gut microbiome. Emerging evidence suggests that bidirectional communication between the gut microbiome and brain is mediated in part by the enteric nervous system [214]. While the enteric nervous system is distinct from the autonomic nervous system, it is similar to the sympathetic and parasympathetic nervous systems in that it is derived from the neural crest [215].…”

Section: The Peripheral Nervous System: a Point Of Convergence Betweementioning

confidence: 99%

“…To fully understand the pathogenesis of ASD comorbidities, greater knowledge of how PCBs and other environmental factors influence the function of peripheral targets is needed (Figure 3). Autonomic disturbances have been linked to gastrointestinal, bladder, and immune dysfunction [214,241,242], suggesting that the PNS may be a convergence point through which environmental factors such as PCBs influence the phenotypic expression of ASD comorbidities. In the context of the bladder, parasympathetic and sympathetic neurons innervate the bladder to control the micturition reflex, and sensory afferent signaling is responsible for the sensation of bladder fullness as well as responses to noxious stimuli within the bladder [243,244].…”

Section: A Role For Pcbs In Asd Comorbidities?mentioning

confidence: 99%

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Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

Panesar

Kennedy

Stietz

et al. 2020

Toxics

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Autism spectrum disorder (ASD) includes a group of multifactorial neurodevelopmental disorders defined clinically by core deficits in social reciprocity and communication, restrictive interests and repetitive behaviors. ASD affects one in 54 children in the United States, one in 89 children in Europe, and one in 277 children in Asia, with an estimated worldwide prevalence of 1–2%. While there is increasing consensus that ASD results from complex gene x environment interactions, the identity of specific environmental risk factors and the mechanisms by which environmental and genetic factors interact to determine individual risk remain critical gaps in our understanding of ASD etiology. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been linked to altered neurodevelopment in humans. Preclinical studies demonstrate that PCBs modulate signaling pathways implicated in ASD and phenocopy the effects of ASD risk genes on critical morphometric determinants of neuronal connectivity, such as dendritic arborization. Here, we review human and experimental evidence identifying PCBs as potential risk factors for ASD and discuss the potential for PCBs to influence not only core symptoms of ASD, but also comorbidities commonly associated with ASD, via effects on the central and peripheral nervous systems, and/or peripheral target tissues, using bladder dysfunction as an example. We also discuss critical data gaps in the literature implicating PCBs as ASD risk factors. Unlike genetic factors, which are currently irreversible, environmental factors are modifiable risks. Therefore, data confirming PCBs as risk factors for ASD may suggest rational approaches for the primary prevention of ASD in genetically susceptible individuals.

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Section: The Peripheral Nervous System: a Point Of Convergence Betweementioning

confidence: 99%

Section: A Role For Pcbs In Asd Comorbidities?mentioning

confidence: 99%

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

Panesar

Kennedy

Stietz

et al. 2020

Toxics

View full text Add to dashboard Cite

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“…The gut microbiome has been found to actively interact with the sympathetic nervous system extrinsic to the gut [ 23 ]. Recent experiments have shown that microbial depletion in the gut leads to increased expression of cFos, a marker of neuronal activity and circuits; colonization of germ-free (GF) mice with gut microflora suppressed this pathway via short-chain fatty acid (SCFA) action in the gut-associated sympathetic ganglia [ 24 ]. Moreover, it is also hypothesized that there is a more direct, bidirectional communication between the gut and the brain via vagal nerves.…”

Section: Gut-brain-axismentioning

confidence: 99%

Gut-Induced Inflammation during Development May Compromise the Blood-Brain Barrier and Predispose to Autism Spectrum Disorder

Eshraghi

Davies

Iyengar

et al. 2020

JCM

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Recently, the gut microbiome has gained considerable interest as one of the major contributors to the pathogenesis of multi-system inflammatory disorders. Several studies have suggested that the gut microbiota plays a role in modulating complex signaling pathways, predominantly via the bidirectional gut-brain-axis (GBA). Subsequent in vivo studies have demonstrated the direct role of altered gut microbes and metabolites in the progression of neurodevelopmental diseases. This review will discuss the most recent advancements in our understanding of the gut microbiome’s clinical significance in regulating blood-brain barrier (BBB) integrity, immunological function, and neurobiological development. In particular, we address the potentially causal role of GBA dysregulation in the pathophysiology of autism spectrum disorder (ASD) through compromising the BBB and immunological abnormalities. A thorough understanding of the complex signaling interactions between gut microbes, metabolites, neural development, immune mediators, and neurobiological functionality will facilitate the development of targeted therapeutic modalities to better understand, prevent, and treat ASD.

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“…The interaction between the host and gut microbiome can influence the central nervous system, modulating the brain and behavior, including mood (Muller et al, 2020 ). Synthetic biology is increasingly seeking to modulate, control and even design (Alnahhas et al, 2020 ) the microbial consortia that form microbiomes.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of the Criminogenic Potential of Synthetic Biology and Routes to Future Crime Prevention

Elgabry

Nesbeth

Johnson

2020

Front. Bioeng. Biotechnol.

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Synthetic biology has the potential to positively transform society in many application areas, including medicine. In common with all revolutionary new technologies, synthetic biology can also enable crime. Like cybercrime, that emerged following the advent of the internet, biocrime can have a significant effect on society, but may also impact on peoples' health. For example, the scale of harm caused by the SARS-CoV-2 pandemic illustrates the potential impact of future biocrime and highlights the need for prevention strategies. Systematic evidence quantifying the crime opportunities posed by synthetic biology has to date been very limited. Here, we systematically reviewed forms of crime that could be facilitated by synthetic biology with a view to informing their prevention. A total of 794 articles from four databases were extracted and a three-step screening phase resulted in 15 studies that met our threshold criterion for thematic synthesis. Within those studies, 13 exploits were identified. Of these, 46% were dependent on technologies characteristic of synthetic biology. Eight potential crime types emerged from the studies: bio-discrimination, cyber-biocrime, bio-malware, biohacking, at-home drug manufacturing, illegal gene editing, genetic blackmail, and neuro-hacking. 14 offender types were identified. For the most commonly identified offenders (>3 mentions) 40% were outsider threats. These observations suggest that synthetic biology presents substantial new offending opportunities. Moreover, that more effective engagement, such as ethical hacking, is needed now to prevent a crime harvest from developing in the future. A framework to address the synthetic biology crime landscape is proposed.

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Microbiota modulate sympathetic neurons via a gut–brain circuit

Cited by 294 publications

References 46 publications

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

Gut-Induced Inflammation during Development May Compromise the Blood-Brain Barrier and Predispose to Autism Spectrum Disorder

A Systematic Review of the Criminogenic Potential of Synthetic Biology and Routes to Future Crime Prevention

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