ABSTRACT Baicalin (BA), a bioactive flavonoid, and levofloxacin hydrochloride (LH), a fluoroquinolone antibiotic, both hold potential for ulcerative colitis (UC) treatment, yet the mechanistic differences in their regulation of gut microbiota and metabolome remain elusive. This study aimed to systematically compare their therapeutic efficacy and underlying mechanisms in a dextran sulfate sodium-induced murine colitis model, with a focus on gut microbial and metabolic modulation. Mice were randomized into Control, model, BA-treated, and LH-treated groups. Disease severity was assessed via body weight changes, disease activity index, colon length, and histopathological analysis. Western blot and enzyme-linked immunosorbent assay were employed to detect NF-κB pathway activation and pro-inflammatory cytokine levels, while 16S rRNA sequencing and metabolomics profiled gut microbiota and metabolites. Both agents markedly ameliorated colitis symptoms, suppressed NF-κB activation, and cytokine expression, with BA showing superior cytokine inhibition. BA enriched beneficial Lactobacillus , regulating isoflavone/alkaloid synthesis; LH elevated Akkermansia abundance and modulated amino acid metabolism. These findings reveal distinct therapeutic mechanisms of BA and LH, laying a foundation for personalized UC therapy and validating BA’s traditional medicinal utility. IMPORTANCE Ulcerative colitis remains a prevalent inflammatory bowel disease with limited microbiota-targeted therapies. Baicalin and levofloxacin both alleviate dextran sulfate sodium-induced colitis, yet their gut microbiome and metabolome regulatory mechanisms have not been directly compared. This study demonstrates that baicalin and levofloxacin exert anti-colitis effects via divergent microbiota-metabolite axes: baicalin enriches Lactobacillus and modulates isoflavone/alkaloid metabolism, while levofloxacin increases Akkermansia and reshapes amino acid metabolism. These distinct mechanisms provide new evidence for developing microbiota-based personalized strategies for ulcerative colitis treatment.
ABSTRACT Standard-of-care serological testing for cryptococcosis includes cryptococcal antigen detection from serum and cerebrospinal fluid (FDA clearance). Diagnosis of pulmonary cryptococcosis remains challenging due to nonspecific clinical presentations and limited sensitivity of conventional testing methods. In a recent study by X. Chen, Z. Wang, C. Di, F. Zhang, et al. (Microbiol Spectr 14:e01083-25, 2026, https://doi.org/10.1128/spectrum.01083-25 ), the authors assessed the performance of cryptococcal antigen testing by immunochromatographic lateral flow assay (CrAg-LFA) on bronchoalveolar lavage fluid (BAL) from 514 patients suspected of having pulmonary cryptococcosis (42 confirmed). While BAL CrAg-LFA testing had high sensitivity (88.1%), similar to serum CrAg-LFA sensitivity (90.5%), combined BAL and serum testing increased the sensitivity to 100% with a 100% negative predictive value. The study suggested that BAL CrAg-LFA may provide added diagnostic value when serum CrAg-LFA is negative, but high suspicion for pulmonary cryptococcosis remains.
ABSTRACT Streptococcus equi subsp. zooepidemicus ( S. zooepidemicus ) is a zoonotic pathogen affecting various mammals, yet its genomic epidemiology remains poorly understood. To address this, we analyzed 428 S. zooepidemicus strains from six countries (1993–2024). The whole-genome single-nucleotide polymorphism (SNP) revealed four clades, with genetic diversity driven by lineage rather than host species or geographic origin. The findings support the conclusion that S. zooepidemicus is a host generalist, with horses serving as the primary host. The identified virulence-associated genes (VAGs) showed clade-specific distribution patterns: clade 1 lacked adherence factor genes srtC.2/3/4 , clade 2 was enriched for the IgG-degrading enzyme gene ideZ , and clade 4 was enriched for a specific allele of the virulence-associated coupling protein gene virD4 . Antimicrobial resistance genes (ARGs) were detected in 18.2% of strains, and no multidrug resistance was found. ARG prevalence was associated with clade 4, with tetracycline resistance being the most common. Mobile genetic elements (MGEs) are pivotal in shaping the accessory genome profiles: prophages function as the primary carriers of exotoxin genes, while integrative and conjugative elements (ICEs) serve as the main vehicles for ARGs. Notably, the co-localization of the invasion-associated virD4 allele and ARGs was identified on ICE Sz 1, predominantly in clade 4 isolates. In conclusion, the pathogenic potential and resistance profiles of S. zooepidemicus are shaped by specific evolutionary lineages driven by MGEs. These elements act not only as genetic cargo but also as drivers that provide the conjugative machinery to co-disseminate virulence and resistance traits, accelerating the evolution of zoonotic lineages. IMPORTANCE S. zooepidemicus is an opportunistic pathogen capable of infecting a wide range of hosts, including humans, often causing severe diseases. This study provides a framework for understanding the evolution of S. zooepidemicus , highlighting that its pathogenic potential and antimicrobial resistance (AMR) profiles are shaped by specific MGE-driven evolutionary lineages. The co-localization of the invasion-associated virD4 allele and ARGs on ICEs indicates that these elements provide both the pathogenic advantage and the conjugative machinery required for horizontal spread in S. zooepidemicus . This suggests that antibiotic selection can promote the transmission of virulent S. zooepidemicus lineages. These findings underscore the need for integrated surveillance strategies to monitor both virulence and AMR traits in S. zooepidemicus within equine populations to benefit public health.
W e read with interest the recent study by de Lira and colleagues (1), which provided insights into the evolution of hybrid pathogenic Escherichia coli (HyPEC). This study described the emergence of atypical enteropathogenic E. coli (aEPEC)/enteroag gregative E. coli (EAEC) through horizontal gene transfer among EAEC and aEPEC CC10 (ST10 and ST8087) during a diarrheal outbreak in São Paulo/Brazil. Concomitant with this publication, we were investigating the genome of a uropatho genic E. coli /EAEC (EC54, JBPBLM000000000) recovered from a urinary tract infection in Roraima/Brazilian Amazon, ~4,600 km from São Paulo. Like the strains in de Lira et al., EC54 belonged to ST10 and carried the same EAEC virulence repertoire, prompting us to investigate whether they correspond to a unique lineage and shared the same EAEC-associated genetic element. To address this question
