Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior

There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders

Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and metabolome in mice

peer-reviewedn-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3−)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3− male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3− offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3− animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes

Food for thought: The role of nutrition in the microbiota-gut–brain axis

Recent research has provided strong evidence for the role of the commensal gut microbiota in brain function and behaviour. Many potential pathways are involved in this bidirectional communication between the gut microbiota and the brain such as immune mechanisms, the vagus nerve and microbial neurometabolite production. Dysbiosis of gut microbial function has been associated with behavioural and neurophysical deficits, therefore research focused on developing novel therapeutic strategies to treat psychiatric disorders by targeting the gut microbiota is rapidly growing. Numerous factors can influence the gut microbiota composition such as health status, mode of birth delivery and genetics, but diet is considered among the most crucial factors impacting on the human gut microbiota from infancy to old age. Thus, dietary interventions may have the potential to modulate psychiatric symptoms associated with gut–brain axis dysfunction. Further clinical and in vivo studies are needed to better understand the mechanisms underlying the link between nutrition, gut microbiota and control of behaviour and mental health

Food for thought: The role of nutrition in the microbiota-gut–brain axis

Recent research has provided strong evidence for the role of the commensal gut microbiota in brain function and behaviour. Many potential pathways are involved in this bidirectional communication between the gut microbiota and the brain such as immune mechanisms, the vagus nerve and microbial neurometabolite production. Dysbiosis of gut microbial function has been associated with behavioural and neurophysical deficits, therefore research focused on developing novel therapeutic strategies to treat psychiatric disorders by targeting the gut microbiota is rapidly growing. Numerous factors can influence the gut microbiota composition such as health status, mode of birth delivery and genetics, but diet is considered among the most crucial factors impacting on the human gut microbiota from infancy to old age. Thus, dietary interventions may have the potential to modulate psychiatric symptoms associated with gut–brain axis dysfunction. Further clinical and in vivo studies are needed to better understand the mechanisms underlying the link between nutrition, gut microbiota and control of behaviour and mental health

Food for thought: The role of nutrition in the microbiota-gut–brain axis

Recent research has provided strong evidence for the role of the commensal gut microbiota in brain function and behaviour. Many potential pathways are involved in this bidirectional communication between the gut microbiota and the brain such as immune mechanisms, the vagus nerve and microbial neurometabolite production. Dysbiosis of gut microbial function has been associated with behavioural and neurophysical deficits, therefore research focused on developing novel therapeutic strategies to treat psychiatric disorders by targeting the gut microbiota is rapidly growing. Numerous factors can influence the gut microbiota composition such as health status, mode of birth delivery and genetics, but diet is considered among the most crucial factors impacting on the human gut microbiota from infancy to old age. Thus, dietary interventions may have the potential to modulate psychiatric symptoms associated with gut–brain axis dysfunction. Further clinical and in vivo studies are needed to better understand the mechanisms underlying the link between nutrition, gut microbiota and control of behaviour and mental health

Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and metabolome in mice.

n-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3-)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3- male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3- offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3- animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes