Haruyuki Nakayama-Imaohji

Aberrant systemic IgG responses to the gut microbiota may be implicated in the pathogenesis of ulcerative colitis (UC). In this study, we investigated IgG-targeted bacteria and their predicted functional characteristics in UC. Using fecal samples and autologous sera from 37 patients with UC and 4 healthy controls, we profiled IgG-targeted bacteria under in vitro conditions using 16S rRNA gene sequencing. To correct for background bacterial abundance, we calculated the IgG+ Probability Score (IPS), which integrates the sample-specific IgG-binding rate to isolate candidate IgG-targeted taxa. Systemic IgG responses were selectively targeted at specific bacterial taxa rather than uniformly directed toward the entire gut microbiota. Active UC and elevated systemic inflammatory markers were associated with increased IPS in oral-associated commensals, including Granulicatella, as well as mucin-degrading taxa. Predictive functional profiling indicated the predicted enrichment of pathways hypothesized to be related to host-derived mucin degradation, capsular polysaccharide biosynthesis, and amino acid biosynthesis. Furthermore, exploratory Random Forest models using IPS features highlighted candidate taxa that differed among clinical parameters (UC exacerbation, Clinical Activity Index, and C-reactive protein), although their classification performance was not independently validated. In conclusion, our in vitro profiling indicates that systemic IgG in UC has the capacity to selectively target specific bacterial taxa associated with disease activity and systemic inflammation. Analyzing the IgG-targeted microbiota via IPS profiling deepens our understanding of host–microbiota interactions in UC and provides a valuable framework for evaluating candidate immune-targeted bacteria associated with disease activity.

Aberrant systemic IgG responses to the gut microbiota may be implicated in the pathogenesis of ulcerative colitis (UC). In this study, we investigated IgG-targeted bacteria and their predicted functional characteristics in UC. Using fecal samples and autologous sera from 37 patients with UC and 4 healthy controls, we profiled IgG-targeted bacteria under in vitro conditions using 16S rRNA gene sequencing. To correct for background bacterial abundance, we calculated the IgG+ Probability Score (IPS), which integrates the sample-specific IgG-binding rate to isolate taxa explicitly targeted by IgG. Systemic IgG responses were selectively targeted at specific bacterial taxa rather than uniformly directed toward the entire gut microbiota. Active UC and elevated systemic inflammatory markers were associated with increased IPS in oral-associated commensals, including Granulicatella, as well as mucin-degrading taxa. Functional profiling indicated the enrichment of pathways related to host-derived mucin degradation, capsular polysaccharide biosynthesis, and amino acid biosynthesis. Furthermore, Random Forest machine learning models utilizing optimized IPS features achieved an area under the curve of 0.817 for predicting UC exacerbation and 0.843 for predicting C-reactive protein elevation. In conclusion, systemic IgG responses in UC were selectively directed toward specific bacterial taxa associated with disease activity and systemic inflammation. Analyzing the IgG-targeted microbiota via IPS profiling deepens our understanding of host-microbiota interactions in UC and provides a valuable framework for evaluating immune-targeted bacteria that fluctuate across different disease phases.

The global prevalence of pulmonary infections caused by non-tuberculous Mycobacteria (NTM), particularly the Mycobacterium avium complex (MAC), is increasing. Since NTM are ubiquitous in moist environments and resistant to standard disinfectants, this study evaluated the efficacy of chlorous acid water (CAW) against them. CAW demonstrated superior sanitizing effects compared to sodium hypochlorite (NaClO), efficiently inactivating NTM at 100 mg/L free available chlorine even in the presence of organic matter, where 1000 mg/L NaClO failed. Instead, subcellular fractionation and protein analysis revealed that CAW penetrates the cell to induce extensive aggregation of internal functional proteins, leading to the rapid collapse of membrane potential and ATP production. Furthermore, CAW exhibited significantly lower cytotoxicity toward human lung-derived A549 cells than NaClO. These results indicate that CAW inactivates NTM effectively by targeting internal protein stability and the respiratory chain, offering a potent and safer disinfection strategy for clinical and domestic environments.

The global prevalence of pulmonary infections caused by non-tuberculous Mycobacteria (NTM), particularly the Mycobacterium avium complex (MAC), is increasing. Since NTM are ubiquitous in moist environments and resistant to standard disinfectants, this study evaluated the efficacy of chlorous acid water (CAW) against them. CAW demonstrated superior sanitizing effects compared to sodium hypochlorite (NaClO). It efficiently inactivated NTM at free available chlorine concentrations of 25 mg/L without organic matter and 100 mg/L with organic matter. In contrast, NaClO at 1000 mg/L failed to inactivate NTM in the presence of organic matter. MAC showed higher resistance to both agents compared to other NTM species. Mechanistically, the bactericidal effect of CAW did not correlate with DNA degradation. While prolonged exposure induced DNA damage, the primary mode of action was identified as a reduction in membrane potential, ATP production, and reactive oxygen species levels without altering cell morphology. These results indicate that CAW inactivates NTM effectively by damaging membrane components and the respiratory chain, rather than targeting DNA.

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease, are chronic disorders relating to gut microbiota dysbiosis. Despite severe pancolitis being more prevalent in pediatric UC than in adults, alterations in the colon mucosa-associated microbiota (MAM) and their association with disease severity remain to be elucidated. The present study aimed to compare the gut microbiota in colon lavage fluids (CLFs) and fecal samples from 19 pediatric UC and 19 non-IBD patients. The community structure of MAM inferred by 16S metagenomic analysis was similar throughout the colon regardless of disease type. Bacterial compositions between MAM and feces were significantly different in non-IBD, while no difference was observed in pediatric UC, indicating a compromised mucous layer that could not sufficiently separate the MAM and luminal microbiota in UC. In pediatric UC, homogenous distribution of MAM was gradually disordered with increases in disease activity or mucosal inflammation, and bacterial groups of upper digestive tract or environmental origin were more abundant in MAM. Monitoring key bacterial markers in MAM, which include Lactobacillus and Enterococcus or Faecalibacterium and Blautia as increased or reduced members in pediatric UC, respectively, might be useful for evaluation of patient prognosis.

Ulcerative colitis (UC) is caused by an excessive immune response to gut microbiota. A recent study reported that the population of IgG-coated gut microbes increases with disease severity in patients with UC, but the role of these IgG-coated microbes in UC pathology is unclear. Serum, feces and colonoscopic lavage fluids (CLFs) were collected from pediatric UC (n = 13) and non-inflammatory bowel disease (IBD) patients (n = 15). Gut microbes were isolated from feces. Serum IgG reactivity to microbial cells and CLF-derived proteins was evaluated by Western blotting. Complement activation by the bacteria–IgG complexes was also assessed. Serum IgG reactivity to gut microbial extracts was highly variable in patients with active UC and increased with mucosal inflammation. IgG reactivity and clinical condition were inversely associated depending on disease activity. Non-IBD patients showed a similar degree of serum IgG response as that seen for patients whose UC was in remission. Lactobacillaceae bound higher amounts of IgG than other gut microbes tested and absorbed IgG to other bacteria. Lacticaseibacillus paracasei suppressed complement activation by Escherichia coli—IgG immune complexes. Appropriate IgG responses to luminal microbes might play a key role in gut microbiota stability by reducing excessive mucosal inflammation.