Microbiome programming of brain development: implications for neurodevelopmental disorders

Abstract

ASDAutism spectrum disorderDuring the last decade, research on germ-free mice has discovered that the gut microbiome (i.e. the normal bacteria colonizing the gastrointestinal tract) can programme brain function and behaviour during early development. At the same time a growing number of clinical studies have shown altered gut microflora in children with autism spectrum disorder (ASD), in combination with altered bacterial metabolites and inflammatory cytokines being part of the gut-brain axis. This review covers the concept of the microbiome; how it is established during childhood; how it is affected by malnutrition; how it can programme the development of the brain through epigenetic mechanisms; which pathways are used from the gut to the brain; and assesses findings that suggest the gut microbiome may be involved in ASD and other neurodevelopmental disorders. This is a new research field with a number of exciting, but so far fragmented, findings indicating the important role of the normal microbiome in shaping the brain. Research also suggests that disruptions of the microbiome may be involved in the aetiology of neurodevelopmental disorders.

A Revolutionizing Approach to Autism Spectrum Disorder Using the Microbiome

“…At the molecular level, the epigenetic modification occurs via two broadly studied mechanisms, which include DNA-methylation and histone modification besides Ribonucleic acid (RNA) interference [28,[115][116][117]. Epigenetic programming of the brain explained through stress-regulating pathways and reduced expression of brain-derived neurotrophic factor (BDNF) by environmental factors during pre-natal and postnatal periods have been thought to exert a long-lasting effect on the neural functioning and behavioural outcome [118,119]. BDNF has a crucial role in the regulation of neurodevelopment, neuronal functions and neuroplasticity and it is frequently associated with depressive disorder and neuroinflammation [120,121].…”

Gut microbiota on gender bias in autism spectrum disorder

“…The metabolites of microbes might be the cause of autism, such as short-chain fatty acids (SCFAs), propionic acid (PPA), acetic acid (AA), and butyric acid (BA). Since SCFAs like PPA and BA, which are present in diet and are fermentation products of many gastrointestinal bacteria, induced extensive changes in gene expression, including neurotransmitter system, neuronal cell adhesion molecule, inflammation, oxidative stress, lipid metabolism, and mitochondrial function, they are playing more and more important roles in host health but also may be environmental contributors in neurodevelopmental disorders including ASD (Alam et al 2017;Forssberg 2019;Nankova et al 2014). Some specific neurotoxicity substances are more likely to infect men with mental disorders such as autism (Mezzelani et al 2015).…”

Establishment of the early-life microbiome: a DOHaD perspective

“…Germ-free mice also show impaired social behaviour and abnormal microglial development. 88 Modulation of the maternal microbiome is sufficient to cause behavioural and neurological changes in the offspring in mice. Administration of non-absorbable antibiotics to pregnant mice reduces exploratory behaviour in their offspring.…”