Biology subjects

Tian, X.

Publications and source records attributed to Tian, X..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Hepatitis E ORF2 blocks trophoblast autophagy to induce miscarriage via LC3B binding rather than PI3K/Akt/mTOR pathway suppression

Hepatitis E virus (HEV) is a zoonotic pathogen that can infect pregnant women and cause adverse pregnancy outcomes, including miscarriage and preterm delivery. The previous study demonstrated that HEV genotype 3 (HEV-3) inhibits complete autophagic flux in both mouse placental tissue and human trophoblast cells (JEG-3), evidenced by reduced expression of ATG proteins (including LC3, Beclin1, ATG4B, ATG5, and ATG9A) and accumulation of p62. However, the specific regulatory pathway involved remains unclear. Thus, eukaryotic expression vectors for HEV open reading frames (ORFs) were constructed, and ORF2 and ORF3 proteins were transiently overexpressed in JEG-3 cells via liposome transfection.. While both ORF2 and ORF3 significantly reduced LC3B protein levels (p < 0.01), only ORF2 induced p62 accumulation (p < 0.01), indicative of autophagic inhibition, which indicates that ORF2 was the key viral protein mediating autophagy suppression in JEG-3. The results of WB and RT-qPCR show that ORF2 suppressed the PI3K/Akt/mTOR pathway while enhancing nuclear translocation of TFEB (p < 0.01) and AMPK phosphorylation (p < 0.01), suggesting paradoxical activation of upstream autophagy regulators. Through co-transfection of mCherry-LC3 with ORF2, co-localization studies, and AlphaFold 3-based intermolecular interaction predictions, we proposed that ORF2 directly binds LC3B to block autophagosome formation. Finally, co-immunoprecipitation confirmed physical interaction between HEV ORF2 and LC3B, elucidating the molecular mechanism of HEV-induced autophagy suppression in trophoblasts. These findings reveal the molecular mechanism by which HEV inhibits autophagy leading to miscarriage in mice, providing new insights into HEV-induced reproductive damage.

pathology↗

bioRxiv2025

PI-FC: Pre-training Individual-specific Functional Connectome through State-invariant Contrastive Learning

Functional MRI enables non-invasive mapping of brain connectivity, yet its clinical translation remains hindered by uncontrolled state-dependent variability that obscures individual-specific signatures during routine scanning. Here we introduce PI-FC -- a deep learning framework leveraging state-invariant contrastive learning to extract stable individual brain signatures across diverse arousal levels, cognitive states, and temporal scales spanning tens of seconds to hours. PI-FC achieves equivalent phenotypic prediction accuracy using substantially reduced scanning time, and eliminates state-dependent effects varying task demands and brain states. Trained on 36,119 subjects across 8 independent datasets, our model demonstrates superior cross-site generalization and outperforms traditional functional connectome (FC) in predicting neuropsychiatric conditions including schizophrenia, autism, depression, and anxiety. Furthermore, PI-FC enables zero-shot inference of brain age, biological sex, and cognitive ability without site-specific retraining. Overall, PI-FC represents a robust, clinically scalable framework that overcomes fundamental barriers to real-world deployment of precision functional neuroimaging.

neuroscience↗

bioRxiv2025

Discovery of A Small Molecule non-IMiD Degrader of ZBTB7A for the Treatment of β-hemoglobinopathies

Sickle cell disease and {beta}-thalassemia, two major {beta}-hemoglobinopathies, pose significant clinical challenges globally. Current treatments often face limitations in efficacy and tolerability. The transcription factor ZBTB7A has emerged as a promising therapeutic target for reactivating fetal hemoglobin expression. Here, we report the discovery and characterization of SH6, a small molecule non-IMiD degrader of ZBTB7A. SH6 induces fetal hemoglobin in erythroid cell lines in a CRBN and ZBTB7A-dependent manner, and it is capable of inducing fetal hemoglobin expression in healthy donor, SCD and {beta}-thalassemia patient CD34+ cell derived erythroid cells. The efficacy of SH6 is confirmed in a xenotransplantation humanized mouse model. SH6 outperforms currently available therapeutic agents in vitro, and shows synergy with hypomethylating agents. SH6 exhibits a favorable in vivo toxicity profile. Our findings establish SH6 as a promising therapeutic lead candidate for further optimization towards clinical development for treatment of sickle cell disease and {beta}-thalassemia.

cell biology↗

bioRxiv2025

Reprogramming Factors Activate a Non-Canonical Oxidative Resilience Pathway That Can Rejuvenate RPEs and Restore Vision

Oct4, Sox2, and Klf4 (OSK) Yamanaka factors induce pluripotency and reverse age-related epigenetic changes, yet the mechanisms by which they promote rejuvenation remain poorly explored. Oxidative stress contributes to CNS aging and retinal pigmented epithelium (RPE) degeneration in age-related macular degeneration. We find that OSK expression in RPE restores retinal structure and visual function in aged mice and promotes oxidative resilience through a non-canonical, Tet2-independent pathway. Integrative functional genomics identifies GSTA4, a detoxifying enzyme that clears the lipid peroxidation byproduct 4-HNE, as a necessary and sufficient OSK effector. Dynamic GSTA4 regulation by OSK recapitulates a stem cell derived stress resilience program. GSTA4 overexpression alone enhances mitochondrial resilience, rejuvenates the aged RPE transcriptome, and reverses visual decline. GSTA4 is consistently upregulated across diverse lifespan-extending interventions suggesting a broader pro-longevity role. These findings uncover a previously unrecognized protective axis driven by Yamanaka factors that circumvents reprogramming, providing therapeutic insights for age-related diseases. HIGHLIGHTSO_LIOSK-GSTA4 provides a dynamic, Tet2-independent stress-resilience axis. C_LIO_LIFunctional genomics pinpoints GSTA4 as a direct downstream effector activated by OSK. C_LIO_LIRPE aging involves progressive accumulation of 4-HNE that can be detoxified by GSTA4. C_LIO_LIEnhancing GSTA4 rejuvenates RPE cells, restores vision and is associated with lifespan-extending interventions. C_LI

genetics↗

bioRxiv2025

Evaluating nongenetic maternal transmission and post-weaning persistence of gut microbiota in cross-fostering rabbits

Gut microbiota is widely recognized as an important source contributing to phenotypic variation of diverse host traits in livestock. In this regarding, it is promising to improve offspring production traits through direct selection on parental individuals with the desirable gut microbiota, and this is termed microbiome breeding. However, the extent of nongenetic maternal transmission of gut microbiota and its post-weaning persistence remains poorly understood. To fill this gap, we cross-fostered 120 newborn rabbits that are offspring of 20 does in this study, and compared gut microbiota of all kits at the weaning (35 days of age) and two weeks post-weaning, respectively. Based on variance component analysis, we found that the large proportions of phenotypic variation of four alpha diversity metrics for kits at weaning can be explained by the nursing does, ranging from 0.218 {+/-} 0.106 for Evenness index to 0.464 {+/-} 0.125 for the number of observed features. The significant effect of nursing does was supported further by comparing three beta diversity metrics among different relationships, using Kruskal-Wallis test and Dunns post-hoc comparisons. In contrast, the biological does showed no significant effect on gut microbiota composition of pre-weaning kits. In post-weaning kits, the influence of nursing does on gut microbiota was not obviously decreased, despite there was increasing contributions of additive genetic effects. In conclusion, this study provides direct evidence in rabbits that offspring gut microbiota is predominantly shaped by the nongenetic maternal transmission, with these maternal influences persisting post-weaning. These results indicate the possibility that the direct selection on parental gut microbiota will alter offspring gut microbiota.

microbiology↗

bioRxiv2025

Learning the native-like codons with a 5'UTR and secondary RNA structure aided species-informed transformer model

Efficient protein expression across heterologous hosts remains a major challenge in synthetic biology, largely due to species-specific differences in codon usage and regulatory sequence context. A key difficulty lies in reconstructing the codon landscape of the target expression system within a foreign host with a native-like codon preference. To address this, we present TransCodon, a Transformer-based deep learning model that leverages both 5 untranslated regions (5UTRs) and coding sequences (CDS), along with explicit species identifiers and RNA secondary structure information, to learn nuanced codon usage patterns across diverse organisms. By incorporating multisource genomic data and modeling sequence dependencies in a masked language modeling paradigm, TransCodon effectively captures both local and global determinants of codon preference. Our experiments demonstrate that integrating species-level information during training significantly improves the models ability to predict optimal synonymous codons when considering different evaluation metrics. More importantly it identifies native-like codons with less divergence from natural sequences compared to other methods. Besides, TransCodon could capture more low-frequency codons which are often omitted by other deep learning-based methods. The results thus indicate that TransCodon as a robust codon language model has the potential for generating native-like CDS with high translational efficiency in target hosts.

bioinformatics↗

bioRxiv2025

A T-cell Intrinsic Role for APOL1 Risk Alleles in Allograft Rejection

African Americans have an increased risk of kidney disease due to exonic variants in Apolipoprotein-L1 (G1 and G2). These prevalent variants have also been linked with kidney rejection, but outside of association with African ancestry, underpinning causal mechanisms are unknown. We investigated T-cell function using transgenic mice with physiologic expression of wild type (G0-), G1-, or G2-APOL1. Mice with variant APOL1 showed greater CD8+T-cell activation with expansion of a central memory (TCM) subset. Stimulated G1-CD8+T-cells showed enhanced proliferation and cytokine production, which reversed with APOL1 inhibition. In MHC-mismatched cardiac transplants, G1-mice demonstrated greater CD8+T-cell infiltration and reduced survival. Bulk transcriptome of G1-CD8+T-cells, and single-cell transcriptome of graft infiltrating TCMs, showed enrichment of canonical T-cell receptor (TCR) pathways including Ca2+-signaling. G1-CD8+T-cells demonstrated baseline ER-Ca2+ depletion followed by sustained increases in cytosolic-Ca2+ upon TCR stimulation. G1-CD8+T-cells were more sensitive to Ca2+ chelation, or store-operated Ca2+ entry inhibition, and relatively resistant to calcineurin antagonism vs. G0-CD8+T-cells. Analogously, in a kidney transplant cohort, APOL1-variant recipients developed rejection when they had elevated peripheral TCMs before transplantation and despite significantly higher tacrolimus levels vs G0/G0-AAs with rejection. In summary, we unravel an excitatory T-cell intrinsic mechanism for APOL1 exonic variants, causally linking them with kidney rejection.

immunology↗

bioRxiv2025

A computational analysis of the glycoprotein LRP1 structure and the role of glycans as quaternary glue

The low-density lipoprotein receptor-related protein 1 (LRP1) plays a critical role in development and transport across the blood-brain barrier (BBB), yet until now, its molecular architecture remained unresolved due to the absence of an experimentally determined structure. Using homology modeling and neural network-based structure prediction algorithms, complemented with molecular dynamics (MD) simulations, we propose a comprehensive model of LRP1 structures. We observe a natural dimerization mechanism and provide insight into the dynamic behavior of its flexible domains under physiological conditions. We investigated the stability of non-covalent interactions keeping LRP1s and {beta} chains linked together, and found the energy required to break the link is 180{+/-}2 kT. The MD characterization highlights the fundamental role of glycans in the creation of LRP1s quaternary structure, increasing the number of intra-dimeric contacts. This study opens new avenues for targeted drug design strategies, enhancing our molecular understanding of LRP1s receptor-mediated transport in the brain and the key mediation of glycosylation in protein-protein interactions.

biophysics↗

bioRxiv2025

Glis3 is a modifier of cyst progression in autosomal dominant polycystic kidney disease

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is caused by mutations affecting polycystin-1 (PC1) or -2 (PC2). The existence of a cilia-dependent cyst activation (CDCA) pathway has been identified by demonstrating that structurally intact primary cilia are crucial for cyst growth following loss of polycystins. We previously used translating ribosome affinity purification (TRAP) RNA-Seq on pre- cystic mouse kidneys to determine the translatome that meet the criteria for CDCA and identified Glis2 as an early effector of polycystin signaling. Here, we investigate the potential role of Glis3 in ADPKD, which, while not transcriptionally altered, encodes a cilia-localized transcription factor belonging to the same family of genes as Glis2. MethodsWe used live cell confocal imaging to study the subcellular localization of Glis3 in the presence or absence of Pkd1. We used Glis3 conditional knockout mice to investigate the genetic interaction between Glis3 and Pkd1. Changes in gene expression and chromatin accessibility were assessed by RNA-Seq and ATAC-Seq on an allelic series of Glis3 and Pkd1 kidney selective inactivation models at 7-weeks age to evaluate the function of Glis3. ResultsThe ciliary localization of Glis3 is not affected by Pkd1 mutation status. Kidney selective Glis3 by itself does not affect kidney structure or function, but dual inactivation of Glis3 and Pkd1 significantly worsen polycystic kidney disease. Integration of transcriptomic profiling and chromatin accessibility assays suggested that kidney tubule specific Glis3 inactivation results in dysregulated fatty acid metabolism and circadian. ConclusionsGlis3 is a primary cilium localized transcription factor that genetically interacts with Pkd1 and modifies kidney epithelial cell metabolism and circadian function.

genetics↗

bioRxiv2025

A Single-cell and Spatially Resolved Cell Atlas of Human Esophageal Squamous Cell Carcinoma

Tumor heterogeneity and the suppressive microenvironment are key challenges that limit the effectiveness of cancer treatment. In this study, we systematically elucidated the molecular characteristics and mechanisms underlying the suppressive immune microenvironment via a combination of single-cell RNA sequencing, spatial transcriptomics, and metabolomics for a series of human esophageal squamous cell carcinoma (ESCC) and matched nontumor tissues. We found that COL17A1+ epithelial cells presented greater malignancy, characterized by triglyceride (TG) and phosphocholine (PC) accumulation. We also identified a tumor-specific POSTN+ fibroblast subgroup. We found a unique epithelial-fibroblast niche with low infiltration of effector immune cells and substantial enrichment of lipids, composed of POSTN+ fibroblasts and COL17A1+ epithelial cells, where their crosstalk contributed to tumor progression. We confirmed that the INHBA/TP63 axis plays a key role in mediating the regulation of COL17A1+ tumor cells by POSTN+ fibroblasts. Our findings provided new insights into the characteristics of the tumor microenvironment and the crosstalk between tumor and fibroblasts, offering valuable multiomics data resources for elucidating tumor progression mechanisms.

genomics↗

bioRxiv2025

Neural hierarchy for coding articulatory dynamics in speech imagery and production

Mental imagery is a hallmark of human cognition, yet the neural mechanisms underlying these internal states remain poorly understood. Speech imagery--the internal simulation of speech without overt articulation--has been proposed to partially share neural substrates with actual speech articulation. However, the precise feature encoding and spatiotemporal dynamics of this neural architecture remain controversial, constraining the understanding of mental states and the development of reliable speech imagery decoders. Here, we leveraged high-resolution electrocorticography recordings to investigate the shared and modality-specific cortical coding of articulatory kinematic trajectories (AKTs) during speech imagery and articulation. Applying a linear model, we identified robust neural dynamics in frontoparietal cortex that encoded AKTs across both modalities. Shared neural populations across the middle premotor cortex, subcentral gyrus, and postcentral-supramarginal junction exhibited consistent spatiotemporal stability during the integrative articulatory planning. In contrast, modality-specific populations for speech imagery and articulation were somatotopically interleaved along the primary sensorimotor cortex, revealing a hierarchical spatiotemporal organization distinct from shared encoding regions. We further developed a generalized neural network to decode multi-population neural dynamics. The model achieved high syllable prediction accuracy for speech imagery (79% median accuracy), closely matching the performance of speech articulation (81%). This model robustly extrapolated AKT decoding to untrained syllables within each modality while demonstrating cross-modal generalization across shared populations. These findings uncover a somato-cognitive hierarchy linking high-level supramodal planning with modality-specific neural manifestation, revolutionizing an imagery-based brain-computer interface that directly decodes thoughts for synthetic telepathy.

neuroscience↗

bioRxiv2025

How Good is AlphaFold3 at Ranking Drug Binding Affinities?

Accurate affinity ranking of small molecules is pivotal for drug discovery. We investigate whether structure prediction models like AlphaFold3, pretrained on protein-ligand interactions, can address this task. Zero-shot evaluation of Protenix (an AlphaFold3-like model) demonstrates superior prioritization of active compounds over conventional scoring functions and state-of-the-art deep learning models. By further fine-tuning Protenix on structure-agnostic protein-ligand bioactivity data from ChEMBL and BindingDB, we develop AlphaRank that predicts pairwise affinity relationships. AlphaRank achieves prediction accuracy comparable to computationally intensive free energy perturbation (FEP+) workflows on standard benchmarks, while requiring substantially less computational resources. Our findings highlight the emergent potential of AlphaFold3-derived models in affinity ranking tasks and emphasize the necessity for targeted methodological exploration to fully harness their capabilities in drug discovery applications.

bioinformatics↗

bioRxiv2025

CRISPRi-Linked Multi-Module Negative Feedback Loops to Address Winner-Take-All Resource Competition

Cellular resource limitations create unintended interactions among synthetic gene circuit modules, compromising circuit modularity. This challenge is particularly pronounced in circuits with positive feedback, where uneven resource allocation can lead to Winner-Takes-All (WTA) behavior, favoring one module at the expense of others. In this study, we experimentally implemented a Negatively Competitive Regulatory (NCR) controller using CRISPR interference (CRISPRi) and evaluated its effectiveness in mitigating WTA behavior in two gene circuits: dual self-activation and cascading bistable switch. We chromosomally integrated a tunable dCas9 gene and designed module-specific gRNAs, with each module encoding its own gRNA to self-repress via competition for limited dCas9. This configuration introduces strong negative feedback to the more active module while reallocating resources to the less active one, promoting balanced module activation. Compared to the control group lacking dCas9-mediated repression, the NCR controller significantly increased module coactivation and suppressed WTA behavior. Our quantitative results demonstrate that NCR provides an effective strategy for regulating resource competition and improving the modularity of synthetic gene circuits.

synthetic biology↗

bioRxiv2025

Neural signature underlying the effect of intranasal vasopressin on emotional responses to spontaneous social comparison

Vasopressin, a key molecular regulator of social behavior, is implicated in promoting self-protective responses to threats against physical safety and resources. However, its role in defending against self-view threats--common in social interactions and critical to well-being--remains unclear. This study investigates the neural mechanisms through which vasopressin modulates self-protective responses to spontaneous social comparison. In a double-blind, placebo-controlled neuroimaging experiment, participants rated their satisfaction with social evaluations and monetary outcomes assigned to a stranger, friend, or themselves. Compared to placebo, vasopressin selectively intensified contrastive emotional responses to social evaluations of the stranger, decreasing satisfaction with positive evaluations and increasing satisfaction with negative evaluations, relative to those of the self or friend. At the neural level, vasopressin reduced the distinctions between the stranger and the self/friend in the medial prefrontal cortex activity, multivariate response patterns, and functional connectivity with the temporoparietal junction and precuneus, with this effect being especially pronounced among socially dominant individuals. These converging neuroimaging findings support the hypothesis that vasopressin alters the neural representation of the stranger, shifting it from a socially irrelevant figure under placebo to a psychologically salient competitor, thereby triggering self-protective emotional processes. These findings elucidate novel neuropsychological mechanisms through which vasopressin amplifies emotional defense against social threats and offer insights into potential clinical applications for psychiatric conditions characterized by impaired self-protection.

neuroscience↗

bioRxiv2025

Non-visually-derived mental objects tax "visual" pointers

In daily life, we can construct mental objects from various modalities: we can create a cat in the mind from visual experience, or from what someone says or signs linguistically. Do mental objects derived from different input sources share the same set of "slots" (or pointers, indexicals)? Employing a novel imagine-one-then-more paradigm in a large EEG sample (N = 52) across two recording sites, we found that increasing the number of imagined objects derived from a non-visual source--auditory speech during eye closure--led to greater suppression of left posterior alpha power. This observation closely mirrors effects previously observed for visually-derived representations. Our results support the existence of a domain-general pointer system that functions as a modality-independent object register in moment-to-moment cognition.

neuroscience↗

bioRxiv2025

Anks3 mediates cilia dependent polycystin signaling and is essential for adult kidney homeostasis

The existence of a cilia-dependent cyst activation (CDCA) pathway underlying autosomal dominant polycystic kidney disease was identified by showing that cyst progression following loss of polycystins is significantly suppressed by removal of structurally intact cilia. We applied translating ribosome affinity purification RNASeq on pre-cystic mouse kidneys to determine a cell-autonomous in vivo translatome associated with CDCA and identified Glis2 as an early effector of polycystin signaling. Here, to discover additional components of CDCA, we used polycystin-dependent Glis2 expression as a functional readout and identified Anks3, from the CDCA pattern translatome, as a candidate cytosolic regulator of polycystin signaling. Anks3 regulates polycystin-dependent Glis2 expression both in vitro and in vivo. Anks3 also undergoes polycystin-dependent changes in phosphorylation state. Inactivation of Anks3 in Pkd1 mouse models suppresses cyst progression, but also results in rapidly progressive kidney injury independent of polycystins. Anks3 inactivation also normalizes a broader spectrum of polycystin-dependent CDCA translatome changes. These findings define Anks3 as a central regulator of cilia dependent polycystin signaling, functioning downstream of cilia and polycystins and upstream of Glis2, and show that Anks3 has broader functions in maintaining renal structural and functional homeostasis.

genetics↗

bioRxiv2025

Unique Gluing Effect of ASXL1 K351 Monoubiquitination Stimulates PR-DUB-Mediated Nucleosomal H2AK119Ub Deubiquitination

Protein ubiquitination plays a critical role in regulating fundamental biological processes through both proteolytic and nonproteolytic mechanisms. While classically known for its role in targeting proteins for degradation, ubiquitination can also modulate enzymatic activity. However, all of the known mechanisms of such modulation involve spatially constrained mechanisms that take place near the enzyme-substrate interfaces. Here, we report an unprecedented regulatory paradigm mediated by ubiquitination that is located distal to the enzyme-substrate interface but can still activate the polycomb repressive deubiquitinase (PR-DUB) complex. Using cryo-electron microscopy, molecular dynamics (MD) simulations, hydrogen-deuterium exchange mass spectrometry (HDX-MS), and kinetics assays, we determined that the ASXL1 K351 monoubiquitination promotes PR-DUB-mediated nucleosomal H2AK119Ub deubiquitination by stabilizing the catalytic pocket of PR-DUB, causing significant increase in maximal catalytic velocity (Vmax) but almost no change in the substrate binding affinity (Km). Structural analysis revealed that the ubiquitin moiety at ASXL1 K351 bridges the BAP1 and ASXL1 subunits, acting as an intramolecular "glue" that constrains the conformational dynamics of these subunits without altering the nucleosome binding interface. Further MD and HDX-MS results demonstrated the monoubiquitination of ASXL1 K351 enables PR-DUB to effectively maintain a spatial arrangement of the catalytic conformation that closely aligns with substrate cleavage. This study expands our understanding of the mechanisms of ubiquitin function to include intramolecular fastening with a molecular gluing effect and provides a deeper mechanistic understanding of PR-DUB activation in nucleosomal H2AK119Ub removal.

biochemistry↗

bioRxiv2025

Gut Microbiome-derived Propionate Reprograms Alveolar MacrophagesMetabolically and Regulates Lung Injury Responses

Responses to lung injury can vary between individuals and the diet and gut microbiome represent two underappreciated sources of inter-individual variability. The gut microbiome can influence lung injury outcomes through the gut-lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that a dietary fiber intervention would enrich for the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria in the gut microbiome, thereby influencing resting lung immunometabolic tone and influence downstream immune responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets and observed changes in the steady-state transcriptional programming of alveolar macrophages (AMs) in the absence of injury. Next, we examined the effects of FR and FF diets on the responses to sterile and infectious lung injury in vivo while simultaneously profiling gut microbiota and SCFA levels transmitted along the gut-lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AMs ex vivo and in vitro. Overall, a FR diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut-lung axis can regulate the resting metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses through the activity of gut metabolites. These results provide further evidence to support the development of therapeutic dietary interventions or the use of specific gut metabolites to preserve or enhance specific aspects of host pulmonary immunity.

immunology↗