Problems with the balance of gut bacteria (the gut flora) early in life may be linked to the development of conditions such as autism and ADHD. This is because the gut and brain are connected in many ways, forming what is known as the “gut-brain axis.” Gut bacteria help produce important chemicals and molecules that influence brain development, the immune system, and even behavior.
Neurodevelopmental disorders (NDs) are conditions that affect the normal development of the central nervous system, usually beginning in childhood and having a profound impact on people’s lives.
They include conditions such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disabilities, and communication disorders.
ASD, characterized by social difficulties and restricted repetitive behaviors and interests, affects 1%–2% of the population, while ADHD is 7% in children and 3.4% in adults, leading to significant physical and mental health burdens.
Communication disorders affect 5%–7% of people and can cause problems with speaking, formulating words, and understanding abstract ideas.
Several prenatal and early-life factors may contribute to the development of ND, making early diagnosis challenging due to the lack of specific biomarkers.
Genetic and environmental factors can disrupt the way the brain adjusts to changes and challenges throughout its development, which is essential for maintaining a healthy balance in nervous system function.
For example, DNA changes inherited from parents or external influences, such as exposure to toxins during pregnancy or early infections, can interfere with this neural adaptation process.
In addition, the immune system, which normally protects the body against disease, can contribute to brain problems. This can occur when there is chronic inflammation or the body produces autoantibodies, which are molecules that mistakenly attack healthy cells, including cells of the nervous system.
These conditions create an unfavorable environment that can disrupt normal brain development and increase the risk of neurodevelopmental disorders.
A substantial subset of individuals with ASD, in particular, experience co-occurring gastrointestinal (GI) symptoms, suggesting a gut-brain connection.
Gut bacteria play a significant role in metabolism, GI health, neurological health, and immune function, suggesting their potential involvement in NDs. Communication between the gut and the brain is a fascinating process and occurs through several biological pathways that connect these two parts of the body.
One such pathway is the vagus nerve, a kind of “highway” that directly connects the central nervous system to the digestive system. Through this connection, chemical and electrical signals can be transmitted, influencing brain and gut functions. Another important form of communication is through molecules produced in the gut, such as short-chain fatty acids (SCFAs).
These substances are created when gut bacteria ferment dietary fiber have effects on metabolism and inflammation, and may even impact the brain. In addition, cytokines (molecules that regulate the immune response), amino acids (the building blocks of proteins), and neurotransmitter precursors (substances that help form the brain’s chemical messengers) also play essential roles in this communication.
For example, microorganisms in the gut are capable of producing neurotransmitters, such as serotonin, that directly affect mood and behavior. Enteroendocrine cells in the gut, which release hormones, and dendritic cells, which are part of the immune system, help coordinate this complex interaction.
These processes can influence the activity of microglia (the brain’s immune cells), thereby regulating the production of neuroactive metabolites—molecules that impact brain function and, by extension, behavior. In short, the gut functions as a second brain, where microbes play an active role in producing substances that modulate both physical health and mental well-being.
Bacterial strains can improve social and anxiety behaviors through impacts on intestinal permeability, the metabolome, and synaptic plasticity. Improvements in GI and ASD-related symptoms were observed in a small pilot study of children diagnosed with ASD following microbiome transfer therapy, with some lasting benefits observed up to 2 years later.
However, the exact contribution of microbiome disruptions to ND disorders remains unclear, with divergent findings in cross-sectional studies of ASD and ADHD.
The connection between early gut microbiota and cognition remains poorly understood, with only three existing investigations and no clinically documented prospective studies of the microbiome of NDs.
Researchers at the University of Florida, using data from the Swedish All Babies in Southeast Sweden (ABIS) cohort, conducted a study that followed more than 16,000 children over 20 years. This study investigated how early life factors, including infections, antibiotic use, and genetic factors, may be linked to the development of NDs.
For the tests, they collected umbilical cord serum, infant feces, family history, and metabolic biomarkers.
The results found associations between the microbiome, immune dysregulation, and early life stress factors with the emergence of NDs.
Newborn gut bacteria. Scanning electron micrograph of a stool culture from a four-day-old baby. SOURCE: https://www.sciencephoto.com/media/893312/view/newborn-baby-s-gut-bacteria-sem
Among the children followed, 1,197 developed some neurodevelopmental disorder, and the researchers identified connections between these conditions and factors such as inflammation, altered metabolism, and changes in the microbiome.
This study highlights the importance of early life factors in the risk of developing NDs and opens doors to future prediction and interventions. With advances in microbiome analysis and biomarkers, there is hope for earlier diagnosis and more effective treatments.
Thus, this research expands our understanding of how the early life environment, including gut health, can shape neurodevelopment and offers new possibilities for preventive and therapeutic approaches.
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Infant microbes and metabolites point to childhood neurodevelopmental disorders
Angelica P. Ahrens, Tuulia Hyötyläinen, Joseph R. Petrone, Kajsa Igelström, Christian D. George, Timothy J. Garrett, Matej Orešič, Eric W. Triplett, and Johnny Ludvigsson
Cell. Volume 187, Issue 8P1853-1873.E15April 11, 2024
DOI: 10.1016/j.cell.2024.02.035
Abstract:
This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.
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