Depicting the composition of gut microbiota in children with tic disorders: an exploratory study

Abstract

Background: Symptom improvement in children with tic disorder (TD) following fecal microbiota transplantation led us to investigate the gut microbiota in TD. This exploratory study aims to depict the gut microbial profile in patients with TD and explore the impact of dopamine receptor antagonist (DRA) drugs on the composition and metabolic function of the gut microbiota. Methods: The gut microbiota were profiled in fecal samples of 49 children with TD and 50 matched healthy controls (HC) using shotgun metagenomic sequencing. A random forest (RF) model was constructed using the gut bacterial species to distinguish TD from HC. Associations between clinical metadata and microbial abundance or function were analyzed using MaAsLin2 and Spearman correlation. Results: The gut microbiota in children with TD was featured by higher abundances of Bacteroides plebeius and Ruminococcus lactaris (a potential pro-inflammatory taxon) and lower abundances of Prevotella stercorea and Streptococcus lutetiensis compared to HC. The constructed RF model accurately distinguished TD from HC based on the gut microbiota profile, resulting in an AUC of 0.884. Significant correlations were observed between tic symptom severity and the abundances of multiple bacterial species and gut microbiota metabolic functions. Multivariate analysis identified an upregulation of 4-aminobutanoate (GABA) degradation in the gut microbiota associated with TD status. The gut microbiota of DRA-treated TD children showed a distinct gut microbiota compared to the treatment-na€ ıve group, represented by an increase in some potential enteric pathogens such as Escherichia coli, a decline in several species including Akkermansia muciniphila, and alterations in various metabolic functions. Conclusions: Bacterial species promoting inflammatory responses and those modulating neurotransmitters such as GABA may be involved in the pathogenesis of TD. The use of DRA drugs is likely to induce overgrowth of some enteric pathogens and alter the gut microbiota metabolism.

Dual-Hit Model of Parkinson’s Disease: Impact of Dysbiosis on 6-Hydroxydopamine-Insulted Mice—Neuroprotective and Anti-Inflammatory Effects of Butyrate

“…Furthermore, P. cinnamivorans, A. furcosa, B. breve , and A. finegoldii were negatively correlated in the network analysis with R. lactaris , recently renamed Faecalicatena lactaris , a member of Clostridium cluster XIVa, a mucin-degrading commensal [ 39 ] that was strongly enriched in 6-OHDA+CFX mice. Although there is a lack of a well-defined role for R. lactaris , some studies associate its enrichment with both chronic gut inflammatory disease and neurodevelopmental disorders [ 40 , 41 , 42 ], suggesting a pro-inflammatory potential for this bacterial species. Here, we can speculate that the increase of R. lactaris in dual-insulted mice can compensate for the decrease of butyrate production bacterial networks by reinforcing mucus glycoprotein degradation and that this activity is detrimental to gut barrier integrity.…”

Emerging trends and focus of human gastrointestinal microbiome research from 2010–2021: a visualized study

“…6 ), the larger landmark nodes can be divided into three categories: population, research methods, and detection methods. A large number of studies have been conducted on the relationship between age (newborn [ 45 ], infant [ 46 ], child [ 47 ], teenager [ 48 ], adult [ 49 ], middle aged [ 50 ] and aged [ 51 ]), gender (male [ 52 ] and female [ 53 ]) and population groups and gastrointestinal microorganisms. This may be related to researchers finding that the gastrointestinal floras of different populations are significantly different, which requires classification to further study the topic.…”

Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling

“…Similarly, exercise-induced stress behavior also caused changes in the abundance of Ruminococcus gnavus, which also modulates intestinal mucus degradation and immune function [ 107 ]. Recent results from metagenomic analysis via shotgun sequencing of fecal samples from 49 children with a tic disorder (TD) and 50 matched healthy controls showed that gut microbiota from TD subjects had a higher abundance of Ruminococcus lactaris and Ruminococcus gnavus [ 108 ]. Clinical evidence also supports a dysregulation in dopamine levels in TD, though the exact effect on dopaminergic neurons, receptors, and transporters is less clear [ 109 ].…”