Bacteroides-dominant gut microbiome of late infancy is associated with enhanced neurodevelopment

Abstract

Dysbiosis of gut microbiota has been retrospectively linked to autism spectrum disorders but the temporal association between gut microbiota and early neurodevelopment in healthy infants is largely unknown. We undertook this study to determine associations between gut microbiota at two critical periods during infancy and neurodevelopment in a general population birth cohort.Here, we analyzed data from 405 infants (199 females) from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study. Neurodevelopmental outcomes were objectively assessed using the Bayley Scale of Infant Development (BSID-III) at 1 and 2 years of age. Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at a mean age of 4 and 12 months.Using clustering methods, we identified three groups of infants based on relative abundance of gut microbiota at 12 months: Proteobacteria-dominant cluster (22.4% higher abundance at 12 months), Firmicutes-dominant cluster (46.0% higher abundance at 12 months) and Bacteroidetes-dominant cluster (31.6% higher abundance at 12 months). Relative to the Proteobacteria-dominant cluster, the Bacteroidetes-dominant cluster was associated with higher scores for cognitive (4.8 points; FDRp = .02), language (4.2 points; FDRp≤0.001), and motor (3.1 points; FDRp = .03) development at age 2 in models adjusted for covariates. When stratified by sex, only male infants with a Bacteroidetes-dominant microbiota had more favorable cognitive (5.9 points, FDRp = .06) and language (7.9 points; FDRp≤0.001) development. Genus Bacteroides abundance in gut microbiota was positively correlated with cognitive and language scores at age 2. Fully adjusted linear mixed model analysis revealed a positive association between Bacteroidetesdominant cluster and change in cognitive and language performance from 1 to 2 years, predominantly among males. No associations were evident between 4-month microbiota clusters and BSID-II scores. Noteworthy is that enhanced sphingolipid synthesis and metabolism, and antagonism or competition between Bacteroides and Streptococcus were characteristic of a Bacteroidetes-dominant gut microbiota.This study found strong evidence of positive associations between Bacteroidetes gut microbiota in late infancy and subsequent neurodevelopment, most prominently among males but not females.

A prospective investigation into the association between the gut microbiome composition and cognitive performance among healthy young adults

“…The two prospective studies, which are both among infants, reported that Firmicutes-dominant and Bacteroidetes-dominant clusters [ 23 ], Bacteroides -dominant cluster [ 18 ], and Bacteroides [ 23 ] were positively associated with a favorable cognitive function. The Bacteroides -dominant cluster of Carlson et al [ 18 ] and our “Erysipelotrichaceae-dominant community I” both have Bacteroides .…”

“…Therefore, more prospective studies where the gut microbiome composition is profiled before the assessment of cognitive performance will help to draw a more definite conclusion and contribute to improving our knowledge on the influence of the gut microbiome on cognitive functioning. Additionally, previous studies have been among infants [ 18 , 23 ], children [ 24 ], middle-aged adults [ 20 ], and older adults [ 15 – 17 , 19 – 22 ]. Considering that the cognitive health in young adulthood positively correlates with memory and brain functioning in later life [ 25 ], studies among young adults would be necessary.…”

The Microbiota-Gut Axis in Premature Infants: Physio-Pathological Implications

“…In the last decades, the number of studies showing the ability of gut commensal microorganisms to modulate the gut-brain connecting pathways along the "microbiotagut-brain axis" during brain development has grown exponentially [108]. This topic is of particular relevance in preterm infants [109], who are at a higher risk of developing neurodevelopmental impairments [110,111], with an increased risk of cerebral palsy and mental disorders. These adverse outcomes may especially involve those babies who are small for gestational age and/or are associated with infection (Figure 1).…”

Metabolic and Neural Mechanisms Underlying the Associations Between Gut Bacteroides and Cognition: A Large-Scale Functional Network Connectivity Study

“…As a transdiagnostic signature of neuropsychiatric disorders ( Williams and Sachdev, 2010 ; Sahakian et al, 2015 ; Gallagher et al, 2017 ), cognitive dysfunction has also been proved to be associated with dysregulation of gut Bacteroides ( Saji et al, 2019 ; Luo et al, 2020 ; Liu et al, 2021 ). Of note, gut Bacteroides and dysregulation of their associated metabolism activities may be related to the pathogenesis of neurodevelopmental disorders ( Dan et al, 2020 ; Jena et al, 2020 ; Tamana et al, 2021 ). Furthermore, Bacteroides -dominant gut microbiome can influence cognition by getting involved in the neurodevelopment during infancy ( Carlson et al, 2018 ; Tamana et al, 2021 ).…”

“…Of note, gut Bacteroides and dysregulation of their associated metabolism activities may be related to the pathogenesis of neurodevelopmental disorders ( Dan et al, 2020 ; Jena et al, 2020 ; Tamana et al, 2021 ). Furthermore, Bacteroides -dominant gut microbiome can influence cognition by getting involved in the neurodevelopment during infancy ( Carlson et al, 2018 ; Tamana et al, 2021 ). Therefore, illuminating the precise metabolic and neural mechanisms underlying the relation between gut Bacteroides and cognition is of high clinical and translational relevance.…”