Researchers from the Azrieli Faculty of Medicine at Bar-Ilan University have now identified a potential link between ASD and the composition of intestinal microbiome. The autism spectrum disorder (ASD), a neurodevelopmental condition characterized by impaired social communication and repetitive behaviors, has long intrigued scientists seeking to unravel its underlying mechanisms.
Potential link between ASD and the composition of the gut microbiome
The researchers analyzed the diversity of the gut microbiome in an Israeli cohort of 96 individuals diagnosed with ASD and 42 neurotypical individuals. Their findings, recently published in the journal npj Biofilms and Microbiomes, highlight significant differences in both alpha and beta diversity in individuals with ASD and identify specific types of bacteria that are found in greater abundance in individuals with autism.
Key findings include an unexpected increase in alpha diversity, a measure of microbial diversity, and a notable increase in the relative abundance of the phylum Bacteriodetes and the genus Bacteroides in individuals with ASD. Traditionally, decreased alpha diversity has been associated with impaired health in various conditions.
However, the increased alpha diversity observed in the ASD cohort challenges prevailing notions, especially considering its potential connection to neurological diseases. Bacteroids, normally present in the human gut microbiome, can have a detrimental impact on health if increased in abundance.
To study the potential functional consequences of these changes in the microbiome, the researchers conducted experiments on newborn mice. Mice treated with Bacteroides fragilis at birth showed dysfunction in social behavior, increased repetitive behaviors, and dysregulation of gene expression.
“Our research suggests that an overabundance of Bacteriodes, particularly early in life, may have functional consequences for individuals with ASD. This sheds new light on the complex interaction between the microbiome and neurodevelopment in individuals with ASD,” said the study's principal investigator, Prof. Evan Elliott, from the Azrieli Faculty of Medicine at Bar-Ilan University. The study was conducted in collaboration with Prof. Omry Koren, a microbiome expert at the Azrieli Faculty.
Interestingly, these effects were observed primarily in male mice, while female mice showed no behavioral deficits, suggesting that males may be more susceptible to environmental factors that contribute to ASD. The research highlights the importance of further investigation into sex-specific aspects of ASD and the potential role of microbial composition.
The implications of this research extend beyond the laboratory, offering potential avenues for further exploration into the long-term effects of microbial interventions during early development and their implications for brain development.
New research has identified significant changes in the gut microbiome of individuals who developed precancerous colon lesions, suggesting a potential connection between gut bacteria and the onset of colorectal lesions and cancers. These findings, presented at UEG Week 2023, open promising new avenues to improve the detection and prevention of colorectal cancer.
The large-scale prospective study, involving 8,208 participants, linked data from the Dutch Microbiome Project with the Dutch national pathology database to identify all registered cases of colon biopsies over the past fifty years.
The researchers analyzed the function and composition of the gut microbiome of individuals who developed precancerous colorectal lesions before fecal sampling between 2000 and 2015 (n=214), as well as those who developed lesions after fecal sampling. between 2015 and 2022 (n=305).
These groups were then compared to individuals with normal colonoscopy results (n = 202) and to the general population. To gain deeper insight into the role of the gut microbiome, researchers are also examining specific bacterial strains and their functions within the gut by reconstructing their genomes from metagenomic data.
The results revealed that individuals who developed colon lesions after fecal sampling showed greater diversity in their gut microbiome than those who did not develop lesions. Furthermore, the composition and function of the microbiome differed between individuals with pre-existing or future injuries and varied by injury type.
In particular, bacterial species of the Lachnospiraceae family and the Roseburia and Eubacterium genera have been linked to future lesion development.
Dr Gacesa, from University Medical Center Groningen and lead author of the study, commented: “Although we did not investigate the mechanisms in this study, it is known from previous research that some of the identified bacterial species may have properties that could contribute to the development of colorectal lesions.”
“A bacterium called Bacteroides fragilis, for example, is known to produce a toxin that can lead to chronic low-grade inflammation in the gut. Prolonged inflammation is thought to be potentially genotoxic and carcinogenic, meaning it can cause genetic damage and promote cancer. ”
Colorectal cancer represents a serious health problem throughout Europe, being the second most common cancer and the second cause of cancer-related death. It typically develops from precancerous lesions within the intestine, making removal of these lesions an effective strategy for preventing colorectal cancer. However, existing noninvasive detection methods, such as fecal immunochemical testing, produce a high number of false positives, leading to unnecessary colonoscopies.
Discussing the implications of the study findings, Dr Gacesa said: “The connection between the gut microbiome and precancerous lesions has been underexplored, leaving uncertainty as to whether gut bacteria can predict the future onset of colorectal
cancer. Our findings suggest that the microbiome could represent a valuable tool for improving existing tests, advancing methods of early diagnosis of precancerous lesions and colorectal cancer.”
Variation in the gut microbiome associated with race and ethnicity appears after three months of age and persists throughout childhood. Bordenstein of Pennsylvania State University, USA, and colleagues.
Variation in the human microbiome has been linked to the incidence, prevalence, and mortality of many diseases and is known to be associated with race and ethnicity in the United States. However, in this context race and ethnicity are considered indicators of inequitable exposure to social and environmental determinants of health due to structural racism. It is unclear when these differences in the microbiome manifest themselves during development and how they relate to early life experiences, including racism.
In the new study, the researchers analyzed data from eight previous studies that, in total, included 2,756 gut microbiome samples from 729 children between the ages of birth and 12 years. Overall, 17.2% of the samples were from non-white individuals, and 14.3% of the samples were from Hispanic individuals.
A machine learning model that analyzed the data identified variability associated with race and ethnicity at or shortly after age three months and could distinguish participants' race and ethnicity with 87% accuracy in based on their microbiomes. Some of the most important bacterial species in this prediction were also associated with breastfeeding and delivery method (vaginal vs. cesarean section).
Of the 57 types of bacteria that varied in abundance among children of different self-identified racial categories, 19 had previously been identified as differentially abundant between white and black adult individuals.
“Notably, our findings do not support variation associated with race or ethnicity that appears at or shortly after birth, when mother-to-child and other mechanisms of vertical microbial transmission are expected to be strongest,” the researchers say. authors.
“Instead, it is very likely that external factors are shaping microbiome variation associated with race and ethnicity within three months or soon thereafter. Our findings highlight the drive to increase the diversity of individuals included in microbiome science studies and support the call for studies that investigate how structural racism and other structural inequities influence microbiome variation and health.”
Mallott says: “The differences we see are not present at birth, or even shortly thereafter. Only two of the 82 microbes that differ by race or ethnicity are maternally transmitted microbes. The vast majority are all microbes that we get from the environment.”
Bordenstein adds: “The analysis presented in this article highlights that studies of the human microbiome have an urgent imperative to prioritize diversity and social science in research from early in life. We want to eventually translate diverse discoveries about the microbiome into shaping the future of healthcare precision, policy, and equity in the diversity of us all.”
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