Dissecting the contribution of host genetics and the microbiome in complex behaviors

Buffington, Shelly A.; Dooling, Sean W.; Sgritta, Martina; Noecker, Cecilia; Murillo, Óscar; Felice, Daniela; Turnbaugh, Peter J.; Costa-Mattioli, Mauro

doi:10.1016/j.cell.2021.02.009

Cited by 134 publications

(103 citation statements)

References 82 publications

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“…Importantly, they further demonstrated that vagal nerve activation was required to translate these signals from the gut into neural changes ( Sgritta et al., 2019 ). Finally, Buffington et al. (2021) found that in Cntnap2 −/− mice (which display decreased sociability and hyperactivity), L. reuteri treatment increased social behaviors, but did not reduce hyperactivity ( Buffington et al., 2021 ), demonstrating behavior- and circuit-specificity.…”

Section: What Role Do Microglia Play In Shaping Social Neural Circuits?mentioning

confidence: 97%

Emerging roles for microglia and microbiota in the development of social circuits

Smith

2021

Brain, Behavior, & Immunity - Health

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Social withdrawal is a core component of the behavioral response to infection. This fact points to a deep evolutionary and biologic relationship between the immune system and the social brain. Indeed, a large body of literature supports such an intimate connection. In particular, immune activation during the perinatal period has been shown to have long-lasting consequences for social behavior, but the neuroimmune mechanisms by which this occurs are only partially understood. Microglia, the resident immune cells of the brain, influence the formation of neural circuits by phagocytosing synaptic and cellular elements, as well as by releasing chemokines and cytokines. Intriguingly, microbiota, especially those that reside within the gut, may also influence brain development via the release of metabolites that travel to the brain, by influencing vagal nerve signaling, or by modulating the host immune system. Here, I will review the work suggesting important roles for microglia and microbiota in social circuit formation during development. I will then highlight avenues for future work in this area, as well as technological advances that extend our capacity to ask mechanistic questions about the relationships between microglia, microbiota, and the social brain.

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Section: What Role Do Microglia Play In Shaping Social Neural Circuits?mentioning

confidence: 97%

Emerging roles for microglia and microbiota in the development of social circuits

Smith

2021

Brain, Behavior, & Immunity - Health

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“…Different approaches for introducing pre-and post-natal alterations in the microbiome and microbial metabolites perturb various social behaviors associated with neurodevelopmental disorders, including ASD, both in humans and mouse models (reviewed in [ 71 ]). For instance, a germ-free humanized mouse model colonized with microbiota from ASD patients promoted ASD-like features, such as decreased communication, increased repetitive behavior, social behavior deficit, and decreased locomotion in an open field [ 28 , 72 ].…”

Section: Drosophila Gm Research Offers Several Advantages For Analyzing Gene-microbiome-brain Interactionsmentioning

confidence: 99%

“…Moreover, selective recolonization of the mice gut with Lactobacillus reuteri reversed the defects in social behavior [ 27 ]. L. reuteri microbial intervention was also recently shown to reverse the social deficits in Cntnap2−/− mouse model of ASD by improving the social reward, perhaps through upregulation of metabolites in the tetrahydrobiopterin pathway [ 28 ]. These studies provide strong support for the bidirectional communication hypothesis between the gut and the brain in ASD.…”

Section: Introductionmentioning

confidence: 99%

The gut-microbiota-brain axis in autism: what Drosophila models can offer?

Salim

Banu

Alwa

et al. 2021

J Neurodevelop Disord

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The idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

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“…Experiments in which a microbial community is transplanted into germ-free mice have opened the door to studies of mechanism and causality in the microbiome. These efforts fall into two categories based on the nature of the transplanted community: studies involving transplantation of complete, undefined communities (i.e., fecal samples) have shown that the microbiome plays a role in a variety of host phenotypes including the response to cancer immunotherapy (Gopalakrishnan et al 2018;Matson et al 2018;Routy et al 2018), caloric harvest (Ridaura et al 2013), colonization resistance to enteric pathogens (Buffie et al 2015), and neural development (Sharon et al 2019;Buffington et al 2021). While illuminating, a limitation of this format is that it is difficult to 'fractionate' an undefined community, making it challenging to discover which strains are involved in a phenotype of interest.…”

Section: Introductionmentioning

confidence: 99%

In vivo augmentation of a complex gut bacterial community

Jain

et al. 2021

Preprint

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Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex but not both, limiting their utility. In accompanying work, we constructed a complex synthetic community (104 strains, hCom1) containing the most common taxa in the human gut microbiome. Here, we used an iterative experimental process to improve hCom1 by filling open metabolic and/or anatomical niches. When we colonized germ-free mice with hCom1 and then challenged it with a human fecal sample, the consortium exhibited surprising stability; 89% of the cells and 58% of the taxa derive from the original community, and the pre- and post-challenge communities share a similar overall structure. We used these data to construct a second version of the community, adding 22 strains that engrafted following fecal challenge and omitting 7 that dropped out (119 strains, hCom2). In gnotobiotic mice, hCom2 exhibited increased stability to fecal challenge and robust colonization resistance against pathogenic Escherichia coli. Mice colonized by hCom2 versus human feces are similar in terms of microbiota-derived metabolites, immune cell profile, and bacterial density in the gut, suggesting that this consortium is a prototype of a model system for the human gut microbiome.

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Dissecting the contribution of host genetics and the microbiome in complex behaviors

Cited by 134 publications

References 82 publications

Emerging roles for microglia and microbiota in the development of social circuits

Emerging roles for microglia and microbiota in the development of social circuits

The gut-microbiota-brain axis in autism: what Drosophila models can offer?

In vivo augmentation of a complex gut bacterial community

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