Biology subjects

Ng, S. C.

Publications and source records attributed to Ng, S. C..

4 recordsLinked to original sources

bioRxiv2025

Maternal IBD-related antibodies are associated with early life gut inflammatory status and microbiota composition: insights from cord blood

PurposeAntibodies in peripheral blood are used to aid in the diagnosis of inflammatory bowel disease (IBD), but their presence in neonatal cord blood and potential effects on early life development remain unknown. MethodsWe measured anti-CBir1, ANCA, anti-OmpC, ASCA IgA, and ASCA IgG levels in the cord blood of babies born to 78 mothers with or without IBD. Their association with fecal calprotectin (FC), and microbiota composition, characterized by 16S rRNA sequencing, was assessed throughout pregnancy and during the first 3 years of life using linear mixed-effects models. ResultsAntibodies were detected in cord blood, with significantly higher levels of anti-CBir1 and ASCA IgG in babies born to mothers with Crohns disease (p = 0.002) and higher abundance of ANCA and anti-OmpC in babies of mothers with ulcerative colitis (p = 0.002), compared to controls. ASCA IgG levels positively correlated with babies FC (p = 0.006), while babies microbiota Shannon diversity was negatively associated with ANCA, anti-OmpC, and ASCA IgA levels (p = 0.003, 0.04, and 0.008, respectively). Romboutsia spp., Citrobacter spp., Pseudomonas spp., Clostridiaceae, Clostridia, and Varibaculum spp. were positively correlated with either or both ANCA and anti-OmpC levels (all multiple testing adjusted q < 0.1). ConclusionOur findings suggest that maternal IBD-associated antibodies cross the placenta barrier and may be associated with intestinal inflammation and imbalanced microbiota colonization. Whether these serological profiles negatively influence the priming of the babys immune system or IBD risk later in life remains to be determined.

immunology↗

bioRxiv2024

Diet outperforms microbial transplant to drive microbiome recovery post-antibiotics

High-fat, low-fiber Western-style diets (WD) induce microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth1,2, which in turn increases risk for a wide array of metabolic3-5, immune6 and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations like antibiotic treatment7,8, although we know little about the mechanism of impairment and the specific host consequences of prolonged post-antibiotic dysbiosis. Here, we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) and WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modeling indicates that RC diet promotes the development of syntrophic cross- feeding interactions, while on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for fecal microbiota transplant (FMT) as a strategy to address dysbiosis and demonstrate that specific dietary interventions are, at minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural, and less invasive alternative to FMT.

microbiology↗

bioRxiv2022

Barrier-properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length

Nup98 FG repeat domains comprise hydrophobic FG motifs linked through uncharged spacers. FG motifs capture nuclear transport receptors (NTRs) during nuclear pore complex (NPC) passage, confer inter-repeat cohesion, and condense the domains into a selective phase with NPC-typical barrier properties. We found that shortening inter-FG spacers enhances cohesion, increases phase density, and tightens such barrier, all consistent with a sieve-like phase. Phase separation tolerated mutating the Nup98-typical GLFG motifs, provided domain-hydrophobicity remained preserved. NTR-entry, however, was sensitive to (certain) deviations from canonical FG motifs, suggesting co-evolutionary adaptation. Unexpectedly, we found arginines to promote FG-phase-entry apparently also by hydrophobic interactions/ H-bonding and not just through cation-{pi} interactions. Although incompatible with NTR{middle dot}cargo complexes, a YG phase displayed remarkable transport selectivity, particularly for engineered GFPNTR-variants. GLFG to FSFG mutations made the FG phase hypercohesive, precluding NTR-entry. Extending spacers relaxed this hypercohesion. Thus, antagonism between cohesion and NTR{middle dot}FG interactions is key to transport selectivity.

biophysics↗

bioRxiv2022

A simple thermodynamic description of phase separation of Nup98 FG domains

The permeability barrier of nuclear pore complexes (NPCs) controls nucleocytoplasmic transport. It retains inert macromolecules but allows facilitated passage of nuclear transport receptors that shuttle cargoes into or out of nuclei. The barrier can be described as a condensed phase assembled from cohesive FG repeat domains, including foremost the charge-depleted FG domain of Nup98. We found that Nup98 FG domains show an LCST-type phase separation, and we provide comprehensive and orthogonal experimental datasets for a quantitative description of this behaviour. A derived thermodynamic model correlates saturation concentration with repeat number, temperature, and ionic strength. It allows estimating the enthalpy, entropy, and{Delta} G ([~]0.2 kJ/mol, 0.1 kB{middle dot}T) contributions per repeat to phase separation and inter-repeat cohesion. While changing the cohesion strength strongly impacts the strictness of barrier, these numbers provide boundary conditions for in-depth modelling not only of barrier assembly but also of NPC passage.

biophysics↗