Biology subjects

Liao, T.

Publications and source records attributed to Liao, T..

18 recordsLinked to original sources

bioRxiv2026

Early Prenatal Cell-Free DNA Methylation Landscape Informs Epigenetic Purification of the Circulating Fetal Genome

Circulating fetal cfDNA is the analyte of a screening test used by millions of pregnant women annually. However, low fetal fraction limits current testing. Fetal cfDNA can be enriched via hypomethylation, but the informative sites require a first-trimester fetal methylome reference. Here we sequenced fetal cfDNA (median purity 94.7%) derived from discarded media from cultured chorionic villus biopsies (n=30) and assembled a first-trimester methylome across 26M CpG methylation sites at a median depth of 207x. We then built an analytical enrichment model that identified millions of CpG markers and assigned predicted enrichment scores. Guided by this model, we adapted epiSIFT as a genome-wide assay selective for unmethylated DNA molecules. In 28 prenatal plasma cases, epiSIFT raised the median fetal fraction from 5.1% to 28.4% (5.6-fold gain) using the top eighth of markers. These findings establish a first-trimester fetal cfDNA methylome reference and demonstrate epigenetic enrichment of the fetal genome.

genomics↗

bioRxiv2026

Conflicts and coalitions among selfish toxin-antidote elements shape the evolution of hyperdivergent haplotypes

Genetic conflict drives evolutionary innovation, yet most research has focused on arms races between selfish elements and their hosts. A second layer-competition among selfish elements-remains largely unexplored. Here, we uncover such a conflict between two antagonistic toxin-antidote elements (TAs), loki-1/sgyn-1 and thor-1/sif-1, in Caenorhabditis tropicalis. Each toxin, LOKI-1 or THOR-1, selectively kills progeny homozygous for the opposing haplotype, favoring heterozygotes. Their antidotes, SGYN-1 and SIF-1, evolved from F-box proteins, although SIF-1 subsequently lost its F-box domain. We solved the crystal structure of the THOR-1-SIF-1 complex and used in vivo mutagenesis to validate the binding interface, supporting direct toxin neutralization independently of F-box-mediated degradation. A survey of 676 wild isolates revealed two contrasting evolutionary outcomes of antagonizing TAs: independently evolved loki-1/sgyn-1 and thor-1/sif-1 remain confined to alternative hyperdivergent haplotypes, whereas other homologous TAs can recombine to form composite haplotypes. Altogether, our findings establish competition among selfish elements as a distinct form of genetic conflict, and support models in which antagonistic TAs act as barriers that restrict gene flow between neighboring populations.

evolutionary biology↗

bioRxiv2026

Evolution of an Aurora Kinase A Inhibitor from an Essential tRNA Synthetase

Gene duplication is a major driver of evolution, yet how it generates fundamentally new molecular functions remains poorly understood. Here, we show how such novelty arose in KLMT-1, a selfish toxin that causes genetic incompatibilities in Caenorhabditis tropicalis. KLMT-1 evolved via duplication of an essential tRNA synthetase but, strikingly, lost its ancestral role in tRNA biology and translation. Instead, KLMT-1 localizes to centrosomes, where it targets Aurora kinase A (AIR-1). This innovation is mediated by a three-amino acid insertion that extends a {beta}-hairpin loop, enabling electrostatic interaction with a regulatory interface on the kinase. Our results demonstrate how changes in selective pressure, combined with minimal modifications in neutrally evolving regions, allow duplicated proteins to access new functional space and evolve entirely new molecular activities.

evolutionary biology↗

bioRxiv2025

From genomic decay to functional advantage: Trait-based evidence for long-term host residency of a next-generation coral probiotic

A key bottleneck in microbiome engineering is ensuring the long-term host association of introduced microbes. Selecting probiotic candidates based on evolutionary genomic decay signatures of emerging host dependency offers a potential solution. The Ruegeria strain B4 of the population MC10, identified by such signatures, has shown persistent colonization in corals in a companion study. Whether this persistence translates into a measurable host benefit compared to other coral-associated Ruegeria strains, and which mechanisms underlie such benefit, remained unknown. Here we directly compare the probiotic efficacy of MC10-B4 against two sympatric Ruegeria strains isolated from the same coral colony and mucus compartment, controlling for host genotype and microenvironment. MC10-B4 inoculation significantly increased heat stress tolerance in the coral model cnidarian Aiptasia (Exaiptasia diaphana strain H2), outperforming both sympatric control strains. To understand the mechanistic basis of this probiotic efficacy, we characterized the functional profile of MC10 using an integrated multi-omics approach. The genome of MC10 is enriched in genes associated with host-interaction, including siderophore-mediated iron acquisition and exopolysaccharide biosynthesis, which were phenotypically confirmed by detectable iron scavenging and enhanced biofilm formation. Following exposure to coral tissue extract, MC10-B4 underwent a coordinated motility-to-sessility proteomic reprogramming, downregulating flagellar motor components while upregulating flagellin and biofilm regulators. This response was distinct from its sympatric relatives, which instead mounted broad upregulation of nutrient acquisition systems. MC10-B4s functional profile, particularly its sensitivity to oxidative stress, contrasts with the traits typically favored in conventional probiotic screens. Our results move beyond the descriptive identification of a coral probiotic by providing initial mechanistic insight into traits associated with long-term host association and improved thermal performance. These findings validate an evolution-guided approach that prioritizes innate colonization potential over pre-defined laboratory functionalities, informing the rational design of durable probiotics.

microbiology↗

bioRxiv2025

Evolutionary Genomics Guides Scalable Coral Probiotics for Climate Resilience

A universal bottleneck limiting probiotic efficacy in medicine, aquaculture, agriculture, and wildlife conservation is uncertain long-term colonization, necessitating repeated administration. We present an evolution-guided framework for probiotic identification based on genomic hallmarks of emerging host dependency, including widespread pseudogenization and insertion sequence proliferation driving genomic restructuring. Applied to coral reefs, we screened over 1,200 coral-associated bacterial isolates and identified Ruegeria MC10 as exhibiting these signatures. Its presence was associated with increased thermal tolerance of a model cnidarian. Following nursery application, MC10 persisted in reef corals for an 8-month monitoring period through a natural bleaching event, improving color retention and retaining algal photosynthesis performance. This work establishes a predictive, scalable pipeline for selecting persistent probiotics, directly addressing a central constraint on microbiome-based interventions across host systems.

microbiology↗

bioRxiv2024

Dating ammonia-oxidizing bacteria with abundant eukaryotic fossils

Evolution of a complete nitrogen cycle relies on the onset of ammonia oxidation, which aerobically converts ammonia to nitrogen oxides. However, accurate estimation of the antiquity of ammonia-oxidizing bacteria (AOB) remains challenging because AOB-specific fossils are absent and bacterial fossils amenable to calibrate bacterial molecular clocks are rare. Leveraging the ancient endosymbiosis of mitochondria and plastid, as well as using state-of-the-art techniques such as the Bayesian sequential dating approach, we obtained a robust timeline of AOB evolution calibrated by fossil-rich eukaryotic lineages. We show that the first AOB evolved in marine Gammaproteobacteria (Gamma-AOB) and emerged between 2.1 and 1.9 billion years ago (Ga), thus postdating the Great Oxidation Event (GOE; 2.4-2.32 Ga). To reconcile the sedimentary nitrogen isotopic signatures of ammonia oxidation occurring near the GOE, we propose that ammonia oxidation likely occurred at the common ancestor of Gamma-AOB and Gammaproteobacterial methanotrophs, or the actinobacterial/verrucomicrobial methanotrophs, which are known to have ammonia oxidation activities. We also do not rule out another possibility that nitrite was transported from the terrestrial habitats where ammonia oxidation by archaea likely took place. Further, we show that the Gamma-AOB predates the anaerobic ammonia oxidizing (anammox) bacteria which also emerged in marine environments, implying that the origin of ammonia oxidation constrained the origin of anammox as nitrite produced by the former fuels the latter. Our robustly calibrated molecular clocks support a new hypothesis that nitrogen redox cycle involving nitrogen oxides evolved rather late in the ocean.

molecular biology↗

bioRxiv2023

Emergence of Prochlorococcus in the Tonian oceans and the initiation of Neoproterozoic oxygenation

Prochlorococcus are the smallest and most abundant photosynthetic organisms on Earth, contributing up to 50% of the chlorophyll in the oligotrophic oceans. Despite being important in regulating the carbon cycle in todays ocean, the ecological significance of Prochlorococcus in Earths history remains elusive. Our new robustly calibrated molecular clock analysis reveals that Prochlorococcus emerged in the deep photic zone of the Tonian (1,000-720 Mya) oceans. The classical light-harvesting antenna complex in Cyanobacteria, i.e., the phycobilisome, was replaced in Prochlorococcus by the chlorophyll{square}based antenna, enabling more efficient use of blue light that penetrates into deeper water. Importantly, Prochlorococcus colonization of deep water enhanced access to phosphate, which was abundant in upwelled seawater, but likely scarce in the Tonian surface ocean, promoting expansion of Prochlorococcus, displacement of incumbent low-light adapted anoxygenic photoferrotrophs, and associated increases in photosynthetic oxygen production. Colonization of deeper waters would also have improved access to ammonium, leading to the neutral loss of nitrate utilization genes. Our research thus documents the conspicuous emergence of new photosynthetic bacterial lineages in the run-up to the Neoproterozoic oxygenation event, implying an additional layer of eco-evolutionary complexity during this pivotal interval in Earths history.

microbiology↗

bioRxiv2023

Deciphering novel TCF4-driven molecular origins and mechanisms underlying a common triplet repeat expansion-mediated disease

Fuchs endothelial corneal dystrophy (FECD) is an age-related cause of vision loss, and the most common repeat expansion-mediated disease in humans characterised to date. Up to 80% of European FECD cases have been attributed to expansion of a non-coding CTG repeat element (termed CTG18.1) located within the ubiquitously expressed transcription factor encoding gene, TCF4. The non-coding nature of the repeat and the transcriptomic complexity of TCF4 have made it extremely challenging to experimentally decipher the molecular mechanisms underlying this disease. Here we comprehensively describe CTG18.1 expansion-driven molecular components of disease within primary patient-derived corneal endothelial cells (CECs), generated from a large cohort of individuals with CTG18.1-expanded (Exp+) and CTG 18.1-independent (Exp-) FECD. We employ long-read, short-read, and spatial transcriptomic techniques to interrogate expansion-specific transcriptomic biomarkers. Interrogation of long-read sequencing and alternative splicing analysis of short-read transcriptomic data together reveals the global extent of altered splicing occurring within Exp+ FECD, and unique transcripts associated with CTG18.1-expansions. Similarly, differential gene expression analysis highlights the total transcriptomic consequences of Exp+ FECD within CECs. Furthermore, differential exon usage, pathway enrichment and spatial transcriptomics reveal TCF4 isoform ratio skewing solely in Exp+ FECD with potential downstream functional consequences. Lastly, exome data from 134 Exp- FECD cases identified rare (minor allele frequency <0.005) and potentially deleterious (CADD>15) TCF4 variants in 7/134 FECD Exp- cases, suggesting that TCF4 variants independent of CTG18.1 may increase FECD risk. In summary, our study supports the hypothesis that at least two distinct pathogenic mechanisms, RNA toxicity and TCF4 isoform-specific dysregulation, both underpin the pathophysiology of FECD. We anticipate these data will inform and guide the development of translational interventions for this common triplet-repeat mediated disease. Authors summaryFuchs endothelial corneal dystrophy (FECD) leads to vision loss and is the most common repeat expansion-mediated disease characterised to date; most individuals with FECD harbour a non-coding CTG repeat expansion within the gene TCF4. FECD represents an important paradigm for other rare and devastating neurological repeat-mediated diseases, given its relatively mild and tissue-specific nature. Intriguingly, despite TCF4 being ubiquitously expressed, individuals with FECD only experience corneal disease, and the biological reason for this tissue-specificity remains elusive. Here, we use tissue from 31 individuals with FECD to perform complementary long-read, short-read and spatial transcriptomic analyses to enhance our understanding of mechanisms underpinning this disease. These data highlight that at least two mechanisms, RNA toxicity and TCF4 isoform dysregulation, underlie the disease state in affected corneal cells. Furthermore, TCF4 isoform skewing, with evidence of downregulation, suggests this mechanism in part may explain the unique vulnerability of the cornea. In addition, 7/134 FECD expansion negative cases were identified to harbour rare and potentially deleterious TCF4 variants, further supporting the hypothesis that dysregulation of TCF4 may be key to FECD pathophysiology. Biological insights presented here will guide the development of personalised FECD therapies and may inform the development of repeat-expansion mediated therapies more broadly.

molecular biology↗

bioRxiv2022

Multicomponent Pseudomonas aeruginosa vaccines eliciting Th17 cells and functional antibody responses confer enhanced protection against experimental acute pneumonia in mice

The Gram-negative pathogen Pseudomonas aeruginosa is a common cause of pneumonia in hospitalized patients. Its increasing antibiotic resistance and widespread occurrence present a pressing need for vaccines. We previously showed that a P. aeruginosa type III secretion system protein, PopB elicits a strong Th17 response in mice after intranasal (IN) immunization and confers antibody-independent protection against pneumonia in mice. In the current study, we evaluated the immunogenicity and protective efficacy in mice of the combination of PopB (purified with its chaperone protein PcrH) and OprF/I, an outer membrane hybrid fusion protein, compared to immunization with the proteins individually either by the intranasal (IN) or subcutaneous (SC) routes. Our results show that after vaccination, a Th17 recall response from splenocytes was detected only in mice vaccinated with PopB/PcrH, either alone or in combination with OprF/I. Mice that were immunized with the combination of PopB/PcrH and OprF/I had enhanced protection in an acute lethal P. aeruginosa pneumonia model, regardless of vaccine route, compared to the mice vaccinated the with either alone or adjuvant control. Immunization generated IgG titers against the vaccine proteins and whole P. aeruginosa cells. Interestingly, none of these antisera had opsonophagocytic killing activity, but antisera from mice immunized with vaccines containing OprF/I had the ability to block IFN-{gamma} binding to OprF/I, a known virulence mechanism. Hence, vaccines combining PopB/PcrH with OprF/I that elicit functional antibodies lead to a broadly and potently protective vaccine against P. aeruginosa pulmonary infections.

immunology↗

bioRxiv2021

KIF2C regulates synaptic plasticity and cognition by mediating dynamic microtubule invasion of dendritic spines

Dynamic microtubules play a critical role in cell structure and function. In nervous system, microtubules specially extend into and out of synapses to regulate synaptic development and plasticity. However, the detailed polymerization especially the depolymerization mechanism that regulates dynamic microtubules in synapses is still unclear. In this study, we find that KIF2C, a dynamic microtubule depolymerization protein without known function in the nervous system, plays a vital role in the structural and functional plasticity of synapses and regulates cognitive function. Using RNAi knockdown and conditional knockout approaches, we showed that KIF2C regulates spine morphology and synaptic membrane expression of AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors. Moreover, KIF2C deficiency leads to impaired excitatory transmission, long-term potentiation, and altered cognitive behaviors in mice. Mechanistically, KIF2C regulates microtubule dynamics and microtubule invasion of spines in neurons by its microtubule depolymerization capability in a neuronal activity-dependent manner. This study explores a novel function of KIF2C in the nervous system and provides an important regulatory mechanism on how microtubule invasion of spines regulates synaptic plasticity and cognition behaviors.

neuroscience↗

bioRxiv2021

Phylogenomics Suggests the Origin of Obligately Anaerobic Anammox Bacteria Correlates with the Great Oxidation Event

The anaerobic ammonium oxidation (anammox) bacteria could transform ammonium and nitrite to dinitrogen gas, and this obligate anaerobic process accounts for up to half of the global nitrogen loss in surface environments. Yet its origin and evolution, which may give important insights into the biogeochemistry of early Earth, remains enigmatic. Here, we performed comprehensive phylogenomic analysis and showed a single origin of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which includes implementing both a traditional cyanobacteria-based and a recently developed mitochondria-based approach, we estimated that anammox bacteria originated at early Proterozoic and most likely around the so-called Great Oxidation Event (GOE; 2.32 to 2.5 billion years ago [Ga]) which fundamentally changed global biogeochemical cycles. We further showed that during the origin of anammox bacteria, genes involved in oxidative stress, bioenergetics and anammox granules formation were recruited, which might have contributed to their survival on an increasingly oxic Earth. Our findings suggest the rising levels of atmospheric oxygen, which made nitrite increasingly available, was a potential driving force for the emergence of anammox bacteria. This is one of the first studies that link the GOE to the evolution of obligate anaerobic bacteria.

microbiology↗

bioRxiv2021

Horizontal gene transfer of a unique nif island drives convergent evolution of free-living N2-fixing Bradyrhizobium

The alphaproteobacterial genus Bradyrhizobium has been best known as N2-fixing members that nodulate legumes, supported by the nif and nod gene clusters. Recent environmental surveys show that Bradyrhizobium represents one of the most abundant free-living bacterial lineages in the worlds soils. However, our understanding of Bradyrhizobium comes largely from symbiotic members, biasing the current knowledge of their ecology and evolution. Here, we report the genomes of 88 Bradyrhizobium strains derived from diverse soil samples, including both nif-carrying and non-nif-carrying free-living (nod free) members. Phylogenomic analyses of these and 252 publicly available Bradyrhizobium genomes indicate that nif-carrying free-living members independently evolved from symbiotic ancestors (carrying both nif and nod) multiple times. Intriguingly, the nif phylogeny shows that all nif-carrying free-living members comprise a cluster which branches off earlier than most symbiotic lineages. These results indicate that horizontal gene transfer (HGT) promotes nif expansion among the free-living Bradyrhizobium and that the free-living nif cluster represents a more ancestral version compared to that in symbiotic lineages. Further evidence for this rampant HGT is that the nif in free-living members consistently co-locate with several important genes involved in coping with oxygen tension which are missing from symbiotic members, and that while in free-living Bradyrhizobium nif and the co-locating genes show a highly conserved gene order, they each have distinct genomic context. Given the dominance of Bradyrhizobium in worlds soils, our findings have implications for global nitrogen cycles and agricultural research.

microbiology↗

bioRxiv2018

Dietary sulfate-driven and gut dysbiosis-triggered breast cancer-related gene upregulation

By gut microbiota metagenomic analysis, we found that the abundance of sulfatase-secreting bacteria (SSB) in the gut of mice fed chondroitin sulfate (CS) increases with significant individual difference. The fluctuation of lipopolysaccharide (LPS) and pro-inflammatory indicators with significant individual and tissue variations was also observed. After mice were fed mixed with CS or injected separately with LPS, the breast cancer-related transcriptional factor genes, BCL11A and RUNX1, were upregulated, whereas the tumor suppressor gene, TP53BP1, were downregulated. Further, the mammary myopithelium marker CK5/6, the mammary hyperplasia marker Ki-67, and other tumor markers were also upregulated. While the exogenous estradiol does not induce the expression of BCL11A, RUNX1, and TP53BP1, the estrogen receptor (ER) agonist Fulvestrant that mimics estradiol action not only elevates estradiol concentrations, but also upregulates tumor marker expression levels, revealing that ER inflammatory inactivation and hyperestrogenemia induction might be the etiological cues of breast cancer origin. This study has preliminarily established a possible correlation of gut microbiota dysbiosis and chronic low-grade inflammation with the early-phase onset of breast cancer in mice. The statistical insignificance of test data was attributed to the individual difference of gut microbiota compositions, which determining the individual and tissue variations of systemic inflammation.

cancer biology↗

bioRxiv2018

tmap: topological analysis of population-scale microbiome data

Population-scale microbiome study poses specific challenges in data analysis, from enterotype analysis, identification of driver species, to microbiome-wide association of host covariates. Application of advanced data mining techniques to high-dimensional complex dataset is expected to meet the rapid advancement in large scale and integrative microbiome research. Here, we present tmap, a topological data analysis framework for population-scale microbiome study. This framework can capture complex shape of large scale microbiome data into a compressive network representation. We also develop network-based statistical analysis for driver species identification and microbiome-wide association analysis. tmap can be used for exploring variations in a population-scale microbiome landscape to study host-microbiome association.\n\nAvailability and implementationtmap is available at GitHub (https://github.com/GPZ-Bioinfo/tmap), accompanied with online documentation and tutorial (http://tmap.readthedocs.io).\n\nContacthttp://hk.zhou@siat.ac.cn

bioinformatics↗

bioRxiv2017

Insulin Does Not Augment In Vitro Tumor Growth Under A Hyperglycemia-Mimicking Milieu And In A Calorie Restriction-Resembling Manner

BackgroundWhether insulin enhances or represses tumor cell proliferation remains debating and inconclusive although epidemiological data indicated insulin use raises a risk of cancer incidence in patients with diabetes mellitus (DM).\n\nMethodology/Principle FindingsWe cultured rat pituitary adenoma cells in a high-glucose medium to simulate hyperglycemia occurring in DM patients. Upon incubation with or without insulin, repressed tumor cell proliferation and downregulated tumor marker expression occur accompanying with mitigated oxidative stress and compromised apoptosis. Mechanistically, insulin resistance-abrogated glucose uptake was suggested to create an intracellular low-glucose milieu, leading to cellular starvation resembling calorie restriction (CR). While downregulation of insulin-like growth factor 1 (IGF-1) occurring in CR was validated, oncogene downregulation and tumor suppressor gene upregulation seen in CR was also replicated by NOS2 knockdown.\n\nConclusions/SignificanceCellular starvation can exert CR-like anti-tumor effects regardless of insulin presence or absence.

cancer biology↗

bioRxiv2017

Artemisinin mimics nitric oxide to reduce adipose weight by targeting mitochondrial complexes

It remains obscure how to medically manage visceral obesity that predisposes metabolic disorders. Here, we show for the first time that a trace amount of artemisinin (0.25 mg/kg) reduces adipose weight in an inflammatory obese mouse model induced by a high-fat diet with lipopolysaccharide (HFD+LPS). HFD+LPS trigger pro-inflammatory responses, upregulate NOS2 expression, elicit potent nitric oxide (NO) burst, and reinforce adipose mitochondrial dysfunctions that facilitate adipogenesis for visceral weight gain. By targeting mitochondrial complexes, artemisinin resembles the NO donor nitroglycerin to exert anti-inflammatory effects, downregulate NOS2 expression, maintain stable NO release, and augment adipose mitochondrial functions that necessitate adipolysis for visceral weight loss. Taken together, artemisinin plays adipose weight-reducing roles by rectifying inflammation-driven mitochondrial dysfunctions.

pharmacology and toxicology↗

bioRxiv2017

Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice

BackgroundAn interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containing O-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks.\n\nResultsA metagenomic gut microbiota analysis revealed the overgrowth of sulfatase-secreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor (TNF-) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver.\n\nConclusionsCS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.

pathology↗

bioRxiv2017

Chondroitin sulfate elicits systemic pathogenesis in mice by interfering with gut microbiota homeostasis

Whether chondroitin sulfate (CS), a common ingredient naturally occurring in livestock and poultry products, improves osteoarthritis remains debating. Here, we show for the first time that CS induces steatogenesis, atherogenesis, and dementia-like pathogenesis in mice. Gut microbiome analysis revealed the sulfatase-secreting bacteria Rikenella and the sulfate-reducing bacteria Desulfovibrio are enriched. Surprisingly, berberine use boosts CS-induced multi-loci inflammatory manifestations by further increasing the abundance of Rikenella and Desulfovibrio, whereas cephalosporin reinforces the colon mucus barrier via flourishing Akkermansia muciniphila and upregulating mucin expression. Mechanistically, berberine aggravates mucus lining injury by prompting mucin degradation, endotoxin leakage, neutralizing antibody induction, pro-inflammatory cytokine burst, lactic acid accumulation and energy currency depletion in multiple organs and tissues. Taken together, CS evokes the early-phase pathogenesis toward steatohepatitis, atherosclerosis, and dementia upon augmenting gut opportunistic infection, and a sustained antibiotic monotherapy does not deprive the risk of CS-driven systemic inflammatory disorders.

pharmacology and toxicology↗