Biology subjects

Barboza, M.

Publications and source records attributed to Barboza, M..

3 recordsLinked to original sources

bioRxiv2026

Neonatal Enteric Infection Disrupts the Microbiota-Gut-Brain Axis Through Pattern Recognition Receptors and Altered Neuroimmune Signaling

Early-life enteric infection can have long-lasting effects on the microbiota-gut-brain (MGB) axis. Using a neonatal Enteropathogenic Escherichia coli (EPEC) model, we show that intestinal epithelial cell (IEC) NOD1 signaling coordinates mucosal immunity, barrier repair, and neuroimmune outcomes throughout early development and into adulthood. Neonates infected at postnatal day (P) 7 exhibited ileal inflammation, as demonstrated by increased expression of inflammatory cytokines (Il1{beta}, Il6, Il12, Il22), chemokines/chemokine receptors (Ccl2, Cxcl1, Ccr2), and barrier-repair genes (Muc2, Slc26a3), with increased monocyte/macrophage infiltration and reduced epithelial proliferation in WT mice that was blunted in Nod1{Delta}IEC mice. Neonatal infection of WT mice induced persistent defects into adulthood (P56), including increased intestinal permeability, sustained inflammatory/repair signatures, hippocampal inflammation, altered neurogenesis, and impaired recognition memory, which were largely absent in Nod1{Delta}IEC mice, establishing a crucial role for IEC NOD1 as a determinant of long-term MGB remodeling. Microbially derived ligands of NOD2, muropeptides, isolated from probiotic Lactobacillus species attenuated EPEC-induced mucosal inflammation and chemokine induction without altering bacterial burden, demonstrating NOD2 host-directed immunomodulation. Together, these findings identify an important role for NOD-dependent signaling axis in the gastrointestinal tract that links early-life infection to enduring gut-brain dysfunction and reveals probiotic-derived muropeptides as candidate microbial therapeutics.

physiology↗

bioRxiv2020

Neonatal enteropathogenic Escherichia coli infection disrupts microbiota-gut-brain axis signaling

BackgroundDiarrheal diseases are a leading cause of death in children under age five worldwide. Repeated early life exposures to diarrheal pathogens can result in co-morbidities including stunted growth and cognitive deficits suggesting an impairment in the microbiota-gut-brain (MGB) axis. MethodsNeonatal C57BL/6 mice were infected with EPEC (strain e2348/69; {Delta}escV [T3SS mutant]), or vehicle (LB broth) via orogastric gavage (105 CFU) at post-natal day (P7). Behavior (novel object recognition [NOR] task, light/dark [L/D] box, and open field test [OFT]), intestinal physiology (Ussing chambers), and the microbiota (16S Illumina sequencing) were assessed in adulthood (6-8 weeks). ResultsNeonatal infection of mice with EPEC impaired recognition memory (NOR task), coupled with increased neurogenesis (Ki67 and doublecortin immunostaining) and neuroinflammation (increased microglia activation [Iba1]) in adulthood. Intestinal pathophysiology was characterized by increased secretory state (short circuit current; Isc) and permeability (conductance; FITC-dextran flux) in the ileum and colon of neonatally EPEC-infected mice, along with increased expression of pro-inflammatory cytokines (Tnf, Il12, Il6) and pattern recognition receptors (Nlr, Tlr). Finally, neonatal EPEC infection caused significant dysbiosis of the gut microbiota, including decreased Firmicutes, in adulthood. ConclusionsTogether these findings demonstrate that infection in early life can significantly impair the MGB axis in adulthood.

microbiology↗

bioRxiv2019

Nod-like receptors are critical for gut-brain axis signaling

Gut-brain axis signaling is critical for maintaining health and homeostasis. Stressful life events can impact gut-brain signaling, leading to altered mood, cognition and intestinal dysfunction. Here we identify nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signaling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, important in the regulation of gastrointestinal (GI) physiology. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal neurogenesis, and reduced neural activation. In addition, NodDKO mice had increased GI permeability and altered serotonin signaling in the gut following exposure to acute stress. Administration of the selective serotonin reuptake inhibitor, fluoxetine, abrogated behavioral impairments and restored serotonin signaling. We also identified that intestinal epithelial cell-specific deletion of Nod1 (VilCre+Nod1f/f), but not Nod2, increased susceptibility to stress-induced anxiety-like behavior and cognitive impairment following exposure to stress. Together these data suggest that intestinal epithelial NLR are novel modulators of gut-brain communication and may serve as potential novel therapeutic targets for the treatment of gut-brain disorders.

physiology↗