Changes in Gut Microbiome Evident in 3 Animal Models of Angelman
Difference between disease and healthy mice, rats, pigs seen in helpful bacteria
Changes in the levels of gut bacteria — the gut microbiome — are evident in small and larger animal models of Angelman syndrome, and these alterations may be related to patients’ gastrointestinal symptoms, a study reported.
A notable difference between disease models and their healthy counterparts was seen in a bacteria called Bifidobacterium that’s considered of importance in maintaining health.
“These findings begin to uncover the underlying mechanistic causes of GI [gastrointestinal] disorders in AS [Angelman syndrome] patients and provide future therapeutic options for AS patients,” the researchers wrote.
The gut microbiome, the diverse collection of bacteria in the intestinal tract, has an essential role in human health and disease, and “alterations in the colonization of the gut microbiome are prevalent in neurodevelopmental disorders,” the team noted.
Constipation among common gastrointestinal symptoms of Angelman
The study, “Unique Features of the Gut Microbiome Characterized in Animal Models of Angelman Syndrome,” was published in the journal mSystems.
Angelman syndrome is caused by the loss or malfunction of the UBE3A gene. Children receive a copy of the UBE3A gene from each biological parent, but only the copy inherited from the mother is active in some parts of the brain. If the maternal gene copy is missing or inactive, brain cells lack gene activity from UBE3A.
In addition to developmental abnormalities, AS patients have gastrointestinal issues, particularly poor feeding associated with muscle weakness of the throat and frequent constipation. These symptoms might be related to changes in gut microbial composition, similar to what has been reported in other conditions caused by defects in a single gene — namely, Prader-Willi syndrome and Rett syndrome.
“The frequency and scope of GI illnesses in AS, however, have never been studied and the diagnostic consensus estimates that the prevalence may affect up to 70% of individuals with AS,” the scientists wrote.
Scientists, led by those at the University of California Davis, compared gut microbiome composition in three Angelman animal models — mice, rats, and pigs — lacking maternal UBE3A gene activity. Disease model animals within each group also were compared to their respective healthy counterparts, serving as controls.
Total bacteria numbers were lower in the mouse model than in the rat and pig models, results showed. In contrast, bacterial diversity was similar between mice and pigs, and significantly higher in rats.
Although a richer and more diverse microbial community was found in AS mice compared to controls, no major differences in microbial composition were identified between AS model animals and healthy controls. This suggests that the overall microbial community remained conserved in AS animals, the scientists noted. Their analysis concerned only bacteria with an overall abundance superior to 1%, they added, so changes may occur in less abundant bacteria.
“Alterations in less-abundant bacteria can potentially change interactions within the gut without affecting the overall microbial community,” the researchers wrote.
Lower levels of lactic acid bacteria evident in disease animal models
Considering the highly abundant groups of bacteria, the team suggested that the main difference between the AS and healthy animals resided in a reduction of lactic acid bacteria, such as Bifidobacterium, which are essential in the gut for maintaining health.
In AS mice, a decrease in Bifidobacterium was coupled with an increase in Bacteroides, similar to what has been described in people with chronic constipation, the scientists said. They suggested these differences in microbial composition are related to AS genetic alterations.
“These findings support a change in the microbial composition associated with the AS genotype,” the team wrote.
A reduction in Bifidobacterium has also been observed in autism spectrum disorder, suggesting that changes in the gut microbial community play a role in neurodevelopmental disorders.
An overall increase in the abundance of Lachnospiraceae Insertae sedis, Desulfovibrio, and Odoribacter was seen in AS animals relative to healthy ones, similar to what has been described in other neurological conditions, such as major depressive disorder, Parkinson’s disease, and attention deficit/hyperactivity disorders.
“Bacterial groups that were significantly altered within the AS models have also been correlated with other neurodegenerative and GI diseases, highlighting their important role in gut-brain communication,” the researchers wrote.
Findings further revealed that gut microbial changes in AS animals affected metabolic processes, including an increase in the production of amino acids — the building blocks of proteins — and the activity of pathways related to the vitamin B complex.
“In conclusion, the microbial composition analysis of AS within three separate animal models showed prominent changes in the composition and metabolic capacity of the gut microbiome compared to those in [wild-type] control animals,” the researchers wrote.
“Bacterial groups that were significantly altered within the AS models have also been correlated with other neurodegenerative and GI diseases, highlighting their important role in gut-brain communication,” they added. “It remains to be determined whether changes to the gut microbiome are a cause or effect” of the gastrointestinal symptoms noted in patients.