Abstract
National screening programs use dried blood specimens to detect metabolic disorders or aberrant protein functions that are not clinically evident in the neonatal period. Similarly, gut microbiota metabolites and immunological acute-phase proteins may reveal latent immune aberrations. Microbial metabolites interact with xenobiotic receptors (i.e., aryl hydrocarbon and pregnane-X) to maintain gastrointestinal tissue health, supported by acute-phase proteins, functioning as sensors of microbial immunomodulation and homeostasis. The delivery (vaginal or cesarean section) shapes the microbial colonization, which substantially modulates both the immune system’s response and mucosal homeostasis. This study profiled microbial metabolites of the kynurenine and tryptophan pathway and acute-phase proteins in 134 neonatal dried blood specimens. We newly established neonatal blood levels of microbial xenobiotic receptors ligands (i.e., indole-3-aldehyde, indole-3-butyric acid, and indole-3-acetamide) on the second day of life. Furthermore, we observed diverse microbial metabolic profiles in neonates born vaginally and via cesarean section, potentially due to microbial immunomodulatory influence. In summary, these findings suggest the supportive role of human gut microbiota in developing and maintaining immune system homeostasis.
Highlights
Dried blood specimens (DBS) are used to quantify circulating levels of drugs (Kloosterboer et al, 2018), metabolites (Sain-van der Velden et al, 2017), and proteins
We profiled TRP, ATA, indole-3-acetic acid (IAA), IAM, IAld, indole-3-butyric acid (IBA), indole-3-lactic acid (ILA), indole-3-propionic acid (IPA), KYN, and NAT levels in 134 neonatal DBS collected on the second day of life (Table 1 and Figure 2A)
No significant differences were observed in metabolite (Figure 2B) and Acute-phase protein (APP) levels (Figure 3B) between cesarean delivery (CD) (n = 20) and vaginal delivery (VD) (n = 114) groups and respective to clinical conditions in mothers and neonates (Supplementary Figures S-4, S-5)
Summary
Dried blood specimens (DBS) are used to quantify circulating levels of drugs (Kloosterboer et al, 2018), metabolites (Sain-van der Velden et al, 2017), and proteins. The composition and timing of gut microbiota colonization vary in VD and CD neonates (Bennet and Nord, 1987; Grönlund et al, 1999; Penders et al, 2006; Palmer et al, 2007; Mitsou et al, 2008). Fecal and vaginal microbiota dominate the initial colonization in VD neonates (Mändar and Mikelsaar, 1996; Bezirtzoglou, 1997; Grönlund et al, 1999; Matsumiya et al, 2002; Wall et al, 2009). The initial microbial composition’s nuances can modulate the immune system’s development and affect the infant’s subsequent health (Francino, 2018; Wampach et al, 2018)
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