Proteobacteria abundance during nursing predicts physical growth and brain volume at one year of age in young rhesus monkeys

Abstract

Over the last decade, multiple studies have highlighted the essential role of gut microbiota in normal infant development. However, the sensitive periods during which gut bacteria are established and become associated with physical growth and maturation of the brain are still poorly defined. This study tracked the assembly of the intestinal microbiota during the initial nursing period, and changes in community structure after transitioning to solid food in infant rhesus monkeys (Macaca mulatta). Anthropometric measures and rectal swabs were obtained at 2-month intervals across the first year of life and bacterial taxa identified by 16S rRNA gene sequencing. At 12 months of age, total brain and cortical regions volumes were quantified through structural magnetic resonance imaging. The bacterial community structure was dynamic and characterized by discrete maturational phases, reflecting an early influence of breast milk and the later transition to solid foods. Commensal microbial taxa varied with diet similar to findings in other animals and human infants; however, monkeys differ in the relative abundances of Lactobacilli and Bifidobacteria, two taxa predominant in breastfed human infants. Higher abundances of taxa in the phylum Proteobacteria during nursing were predictive of slower growth trajectories and smaller brain volumes at one year of age. Our findings define discrete phases of microbial succession in infant monkeys and suggest there may be a critical period during nursing when endogenous differences in certain taxa can shift the community structure and influence the pace of physical growth and the maturational trajectory of the brain.

Significant Microbial Changes Are Evident in the Reproductive Tract of Pregnant Rhesus Monkeys at Mid-Gestation but Their Gut Microbiome Does Not Shift until Late Gestation

“…Our findings on bacterial changes in the reproductive and digestive tracts of pregnant monkeys concur with many previous papers reporting significant shifts during pregnancy, both in women and other animal species [ 69 , 70 , 71 , 72 ]. However, the vaginal alterations in pregnant rhesus monkeys did not involve the increased dominance of lactobacilli that is usually observed in healthy women, but rather a further enhancement of the microbial diversity already evident in the cycling female monkeys prior to conception [ 24 , 34 , 73 ]. KEGG analyses of the bacterial genes that would accompany the increased bacterial diversity suggested that differences in taxonomic composition could potentially impact several metabolic pathways in the reproductive tract, as well as influence protein signaling to the placenta and contribute to the immunomodulation needed to prevent maternal rejection of the fetus.…”

“…Monkeys typically have a median of 10 different taxa in the lower genital tract (with a range of 6–19 genera) [ 24 ]. The presence of these bacteria is not typically associated with adverse symptoms, despite the presence of substantial amounts of sialidase enzyme activity in their cervico-vaginal fluid, which is a common clinical marker of bacterial vaginosis in women [ 34 ]. The presence of diverse taxa in the vagina of monkeys, including many that are more typically associated with the intestines, may occur because monkeys are quadrupedal.…”

“…Swabs were placed immediately on wet ice and stored frozen in an ultracold freezer at below 70 • C. All specimens from an entire experiment were processed and sequenced as a single batch. The DNA isolation protocol was published previously [33,34], and is detailed in Supplemental Materials-Methods. Microbial DNA was isolated in Study 1a and 1b using the PowerSoil DNA isolation kit (MoBio, Carlsbad, CA, USA).…”

Gut brain interaction theory reveals gut microbiota mediated neurogenesis and traditional Chinese medicine research strategies

“…Changes in Proteobacteria can predict changes in the total brain and cortex of rhesus monkeys in infancy ( Rendina et al., 2021 ). Proteobacteria levels differ between healthy individuals, and those with mild cognitive impairment and AD; these difference gradually increase with disease deterioration ( Guo et al., 2020 ).…”

The Relationship Between the Preterm Infant Gut Microbiome and Later Childhood Behavior

“…Disruption of host-microbe interplay at an early age may have lifelong consequences for distal organs, such as the brain 14 . Proteobacteria in the early life of infant rhesus monkeys predicted a slower growth trajectory and smaller brain volumes at one year of age 15 . Proin ammatory bacterial metabolites from the gut can alter the blood brain barrier or cross into the brain, altering microglia, and contributing to the development of neurological injury 16 which then translates into later neurodevelopmental and behavioral problems.…”