Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status

Abstract

Although thimerosal, an ethylmercury-based preservative, has been removed from most pediatric vaccines in the United States, some multidose vaccines, such as influenza vaccines, still contain thimerosal. Considering that a growing number of studies indicate involvement of the gut microbiome in infant immune development and vaccine responses, it is important to elucidate the impact of pediatric vaccines, including thimerosal-containing vaccines, on gut microbial structure and function. Here, a non-human primate model was utilized to assess how two vaccine schedules affect the gut microbiome in infants (5–9 days old) and juveniles (77–88 weeks old) through 16S ribosomal RNA sequencing and metabolomics analyses of the fecal samples. Two treatment groups (n = 12/group) followed either the vaccine schedule that was in place during the 1990s (intensive exposure to thimerosal) or an expanded schedule administered in 2008 (prenatal and postnatal exposure to thimerosal mainly via influenza vaccines), and were compared with a control group (n = 16) that received saline injections. The primary impact on gut microbial structure and function was age. Although a few statistically significant impacts of the two common pediatric vaccine schedules were observed when confounding factors were considered, the magnitude of the differences was small, and appeared to be positive with vaccination.

Dietary forage to concentrate ratios impact on yak ruminal microbiota and metabolites

“…In the arginine and proline metabolism pathway, arginine is degraded by arginase to ornithine, which is metabolized to produce γ -aminobuytric acid (GABA). The 4-acetamidobutanoic acid is a derivative of GABA, which is an important mediator of arginine and proline metabolism ( Gao et al, 2017 ); GABA acts as an excitatory transmitter in the early stages of life and is involved in brain development ( Hasegawa et al, 2018 ). In our study, 4-acetamidobutanoic acid was positively correlated with Rikenellaceae_RC9_gut_group, which belongs to Rikenellaceae and produces short-chain fatty acids (SCFAs) to provide more energy, which has a positive effect on arginine and proline metabolism.…”

Gut microbiota are associated with sex and age of host: Evidence from semi‐provisioned rhesus macaques in southwest Guangxi, China

“…Age is also associated with the gut microbiota of mammals (Byrd et al., 2020; Hasegawa et al., 2018). This has been documented in humans (de la Cuesta‐Zuluaga et al., 2019) and nonhuman primates, such as wild western lowland gorillas ( Gorilla gorilla gorilla ) (Pafčo et al., 2019), black howler monkeys ( Alouatta pigra ) (Amato et al., 2014), and Tibetan macaques ( Macaca thibetana ) (Sun et al., 2018).…”

“…In addition, different age classes are differentially affected by hormones, especially during puberty (Vandenberg et al., 2012). Therefore, studies of the gut microbiota need to consider the effects of age on digestive ecology (Byrd et al., 2020; Hasegawa et al., 2018).…”

“…In addition to diet, factors that influence the gut microbiota of rhesus macaque include interspecific differences in physiology (Chen et al., 2020b; Cui et al., 2019) and environment (Chen et al., 2020a; Zhao et al., 2018). While age and sex are known to influence gut microbiota composition (Byrd et al., 2020; de la Cuesta‐Zuluaga et al., 2019; Hasegawa et al., 2018), more research is needed on this relationship in nonhuman primates. Particularly for species used as animal models, disregarding sex and/or age information may exacerbate the risk of obtaining false positives in gut microbiota studies of human disease (Vujkovic‐Cvijin et al., 2020).…”

Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?

“…For oral rotavirus vaccination, the vaccine does not seem to have any impact on the human infant gut microbiota [175,176]. In a NHP model, two anti-influenza vaccine schedules had little impact on the gut microbiota of infant and juvenile rhesus macaques [177]. On the contrary, in the adult NHP, a mucosal SIV or HIV-1 vaccination protocol has been shown to alter the rectal microbiome.…”