Ubiquitin-specific protease 11 structure in complex with an engineered substrate mimetic reveals a molecular feature for deubiquitination selectivity.

Ubiquitin-specific proteases (USPs) are crucial for controlling cellular proteostasis and signaling pathways but how deubiquitination is selective remains poorly understood, in particular between paralogues. Here, we developed a fusion tag method by mining the Protein Data Bank and trapped USP11, a key regulator of DNA double-strand break repair, in complex with a novel engineered substrate mimetic. Together, this enabled structure determination of USP11 as a Michaelis-like complex that revealed key S1 and S1' binding site interactions with a substrate. Combined mutational, enzymatic, and binding experiments identified Met77 in linear diubiquitin as a significant residue that leads to substrate discrimination. We identified an aspartate "gatekeeper" residue in the S1' site of USP11 as a contributing feature for discriminating against linear diubiquitin. When mutated to a glycine, the corresponding residue in paralog USP15, USP11 acquired elevated activity toward linear diubiquitin in-gel shift assays, but not controls. The reverse mutation in USP15 confirmed that this position confers paralog-specific differences impacting diubiquitin cleavage rates. The results advance our understanding of the molecular basis for the higher selectivity of USP11 compared to USP15 and may aid targeted inhibitor development. Moreover, the reported carrier-based crystallization strategy may be applicable to other challenging targets.

Does the local government multi-objective competition intensify the transfer of polluting industries in the Yangtze River Economic Belt?

Exploring the effect of local government multi-objective competition on the transfer of polluting industries is of great practical significance for promoting the high-quality development in the Yangtze River Economic Belt. This paper adopted the extended shift-share analysis method to measure the scale of inter-provincial transfer of polluting industries in the Yangtze River Economic Belt from 2008 to 2020. Considering local governments' economic, innovation, talent and environmental protection competition, the paper examined the effects of local government multi-objective competition on the transfer of polluting industries in the region, and tested its spatial spillover effects. The results showed that: 1. Different competitions had different effects on the transfer of polluting industries. Economic competition intensified the transfer of polluting industries, while talent, innovation, and environmental protection competition all restrained it, among which environmental protection competition had the strongest restraining effect. 2. Compared with the transfer of polluting industries, the direction of economic competition and environmental protection competition on the transfer of industries did not change, but the degree of influence was reduced, talent competition instead promoted industrial transfer of the research region to some extent. 3. From the basin level, government competition in the upstream region more obviously intensified the transfer of polluting industries; while from the economic scale level, the restraining effect of government competition in the developed region on the transfer of polluting industries was much stronger. 4. Both innovation and environmental protection competition had positive spatial spillover effects. Therefore, it is necessary to optimize the promotion and assessment mechanism of local officials, adopt differentiated competitive constraint mechanisms in accordance with local conditions, guide local governments to transform their development concepts, promote the sharing and common use of technological innovations, and promote the orderly transfer of industries in the Yangtze River Economic Belt.

Hydrogen inhalation therapy regulates lactic acid metabolism following subarachnoid hemorrhage through the HIF-1α pathway.

The neuroprotective effects of hydrogen have been demonstrated, but the mechanism is still poorly understood. In a clinical trial of inhaled hydrogen in patients with subarachnoid hemorrhage (SAH), we found that hydrogen reduced the accumulation of lactic acid in the nervous system. There are no studies demonstrating the regulatory effect of hydrogen on lactate and in this study we hope to further clarify the mechanism by which hydrogen regulates lactate metabolism. In cell experiments, PCR and Western Blot showed that HIF-1α was the target related to lactic acid metabolism that changed the most before and after hydrogen intervention. HIF-1α levels were suppressed by hydrogen intervention treatment. Activation of HIF-1α inhibited the lactic acid-lowering effect of hydrogen. We have also demonstrated the lactic acid-lowering effect of hydrogen in animal studies. Our work clarifies that hydrogen can regulate lactate metabolism via the HIF-1αpathway, providing new insights into the neuroprotective mechanisms of hydrogen.

Comparative efficacy and safety of combination therapy with infliximab for Crohn's disease: a systematic review and network meta-analysis.

PURPOSE: There is not enough information to position medications for the treatment of Crohn's disease (CD). Therefore, using a network meta-analysis and systematic review, we evaluated the efficacy and safety of combination therapy and infliximab (IFX) monotherapy in CD patients. METHODS: We identified randomized controlled trials (RCTs) in CD patients who were given IFX-containing combination therapy versus IFX monotherapy. Induction and maintenance of clinical remission were the efficacy outcomes, while adverse events were the safety outcomes. The surface under cumulative ranking (SUCRA) probabilities was used to assess ranking in the network meta-analysis. RESULTS: In total, 15 RCTs with 1586 CD patients were included in this study. There was no statistical difference between different combination therapies in induction and maintenance of remission. In terms of inducing clinical remission, IFX + EN (SUCRA: 0.91) ranked highest; in terms of maintaining clinical remission, IFX + AZA (SUCRA: 0.85) ranked highest. There was no treatment that was significantly safer than the others. In terms of any adverse events, serious adverse events, serious infections, and infusion/injection-site reactions, IFX + AZA (SUCRA: 0.36, 0.12, 0.19, and 0.24) was ranked lowest for all risks; while IFX + MTX (SUCRA: 0.34, 0.06, 0.13, 0.08, 0.34, and 0.08) was rated lowest for risk of abdominal pain, arthralgia, headache, nausea, pyrexia, and upper respiratory tract infection. CONCLUSION: Indirect comparisons suggested that efficacy and safety of different combination treatments are comparable in CD patients. For maintenance therapies, IFX + AZA was ranked highest for clinical remission and lowest for adverse events. Further head-to-head trials are required.

Temperature effects on axial dispersion in a photopolymer-based holographic lens.

This study aims to discover whether temperature has an effect on axial dispersion in a photopolymer-based holographic lens. A typical coaxial holographic lens is recorded in the acrylamide polymer system. The axial dispersion spectrum is read and collected by using a supercontinuum source and spectrometer. The temperature effects on axial dispersion in a photopolymer-based holographic lens are investigated experimentally. With increasing temperature from 23°C to 70°C, the diffraction spectrum shifts, and the axial dispersion is shortened evidently. The peak wavelength of the dispersion spectrum shifts from 629.05 to 612.50 nm with an obvious blueshift of 16.55 nm. The spatial position of the peak wavelength also decreases from around 40 to 22 mm from the material surface. Simultaneously, the position sensitivity of the device reduces from 2.53 to 1.50 nm/mm. The shortening of the effective focal length and reduction of the diffraction intensity indicate that the high temperature above 40°C is a disadvantageous factor for actual use of a holographic lens-based spectral confocal measuring device. In practical application, a constant temperature is a significant means to ensure the measurement accuracy and range.

Endoplasmic reticulum stress regulates pyroptosis in BPDE-induced BEAS-2B cells.

Benzo(a)pyrene(B(a)P), as the main representative of polycyclic aromatic hydrocarbons, can promote inflammation and many chronic pulmonary diseases. However, the underlying mechanism of Benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE)-induced human bronchial epithelial cell pyroptosis related to endoplasmic reticulum stress (ERS) has not been elucidated. This study focused on the effects of BPDE on ERS and pyroptosis in human bronchial epithelial cells (BEAS-2B), and explored the relationship between ERS and pyroptosis. BEAS-2B cells were stimulated with 0.50, 0.75, and 1.00 µmol/L BPDE for 24 h to detect ERS and pyroptosis. After inhibition of ERS with 4-phenylbutyrate (4-PBA), pyroptosis of BEAS-2B cells was tested. The results showed that BPDE decreased the cell viability, changed the morphological structure of endoplasmic reticulum and increased the expression levels of GRP78 and p-PERK. After BPDE treatment, the cell membrane was damaged and incomplete under transmission electron microscope; Hoechst 33342/PI fluorescence staining showed that the number of PI-positive cells was enhanced. The expression levels of GSDMD-N, cleaved-caspase 1, and cleaved-IL-1ß were elevated, and the expression levels of IL-1ß, IL-18, and NLRP3 protein were improved. In BPDE combined with 4-PBA intervention group, the rate of PI-positive cells was reduced, the expression levels of GRP78, GSDMD-N, and cleaved-caspase 1 were decreased, and the expression levels of IL-1ß, IL-18, and NLRP3 were decreased. In conclusion, BPDE could induce ERS and pyroptosis in BEAS-2B cells, and ERS may promote the occurrence of BPDE-induced pyroptosis.

Accumulation and translocation of food chain in soil-mulberry (Morus alba L.)-silkworm (Bombyx mori) under single and combined stress of lead and cadmium.

In recent years, heavy metal pollution has caused immeasurable harm to the environment. As an emerging technology, phytoremediation technology has gained a place in the treatment of heavy metal pollution with its unique advantages. This study analyzes the toxic effects of mulberry (Morus alba) seeds, seedling growth and silkworm under heavy metal stress of lead (Pb) and cadmium (Cd), and explore the accumulation and migration of Pb and Cd in the soil-mulberry tree-silkworm system. The main results were as follows: (1) Seed germination and potted seedling experiments were conducted under heavy metal Pb and Cd stresses, and it was found that Pb and Cd had inhibitory effects on mulberry seed germination, growth and photosynthesis of mulberry seedlings, and as the concentration of heavy metals increased, the stronger the inhibitory effect. Moreover, Pb and Cd have a synergistic effect under compound stress. (2) The accumulation and transfer rules of Pb and Cd ions in mulberry were different. The content of Pb in mulberry was root > leaf > stem and the content of Cd was root > stem > leaf. The combined stress promoted the transfer of Pb and Cd from the underground part to the aerial portion of mulberry. (3) The silkworm feeds on mulberry leaves contaminated with heavy metals in this experiment and found that: with the increase of silkworm feeding, the heavy metal content in the silkworm body increased significantly, but the content remained in the silkworm body was less, most of it was excreted with silkworm excrement. Combined stress has no significant effect on the detoxification mechanism of silkworm. It is indispensable to think of the synergistic effect of heavy metals on plants germination when seeds are used for phytoremediation.

An iridium(III) complex/G-quadruplex ensemble for detection of ochratoxin A based on long-lifetime luminescent.

A G-quadruplex-based platform has been developed for the time-resolved monitoring of ochratoxin A (OTA). The simple platform displays good sensitivity for OTA with a detection limit of 40 nM via steady-state emission spectroscopy. Notably, the platform showed a detection limit of 10.8 nM via time-resolved emission spectroscopy (TRES), which is about 4 times more sensitive than steady-state mode. Moreover, the probe showed excellent selectivity for OTA over other mycotoxins. Furthermore, OTA was successfully detected in actual herbal plant extracts samples. Our platform is the first to detect OTA using TRES to distinguish between the target signals versus the auto-fluorescence of real samples. This platform shows improved detection speed, accuracy and sensitivity with simple operation, low cost, and no requirement for complicated pre-processing.

LncRNA-ENST00000501520 promotes the proliferation of malignant-transformed BEAS-2B cells induced with coal tar pitch mediated by target genes.

As a human carcinogen, coal tar pitch (CTP) can significantly increase the risk of lung cancer. However, the mechanism underlying CTP-induced lung carcinogenesis has not been well understood. This study aims to explore the role of the LncRNA-ENST00000501520 in the proliferation of malignant-transformed human bronchial epithelial cells (BAES-2B) induced by CTP extract for the first time. BEAS-2B cells were stimulated with 2.4 µg/mL CTP extract, and then passaged for three times, which were named passage 1 and then passaged until passage 30 (named as CTP group). The ENST000001520 of cells in CTP group was interfered using siRNA. The results showed that ENST000001520 located in cell nucleus (>80%) had no or weak ability of protein encoding. After interference of ENST000001520, the migration and proliferation of cells in CTP group were inhibited, and the cell cycle was arrested in the G0/G1 phase; however, the apoptosis of cells in CTP group was promoted. The target genes (SKB1, CLTB, TAP2, PIPK2, and SOCS3) of ENST000001520 were screened out, and the mRNA and protein expression of SBK1 and SOCS3 was significantly decreased after ENST000001520 interference. SBK1 and SOCS3 may play a promoting role in occurrence and development of cancers. The study suggests that LncRNA-ENST00000501520 could promote the proliferation in malignant-transformed BEAS-2B cells induced with CTP extract which may be mediated by target genes. This study may provide a new target for prevention and treatment of lung cancer.

Emerging Screening Approaches in the Development of Nrf2-Keap1 Protein-Protein Interaction Inhibitors.

Due to role of the Keap1-Nrf2 protein-protein interaction (PPI) in protecting cells from oxidative stress, the development of small molecule inhibitors that inhibit this interaction has arisen as a viable approach to combat maladies caused by oxidative stress, such as cancers, neurodegenerative disease and diabetes. To obtain specific and genuine Keap1-Nrf2 inhibitors, many efforts have been made towards developing new screening approaches. However, there is no inhibitor for this target entering the clinic for the treatment of human diseases. New strategies to identify novel bioactive compounds from large molecular databases and accelerate the developmental process of the clinical application of Keap1-Nrf2 protein-protein interaction inhibitors are greatly needed. In this review, we have summarized virtual screening and other methods for discovering new lead compounds against the Keap1-Nrf2 protein-protein interaction. We also discuss the advantages and limitations of different strategies, and the potential of this PPI as a drug target in disease therapy.

Rhodium(III)-Based Inhibitor of the JMJD3-H3K27me3 Interaction and Modulator of the Inflammatory Response.

We describe in this study a rhodium(III) complex 1 as a new JMJD3 inhibitor and proinflammatory mediator. Complex 1 selectively inhibited the demethylation of H3K27me3 over other similar substrates, indicating its selectivity for JMJD3 over other histone demethylases, including JMJD2D and KDM5A. In terms of mechanism, complex 1 inhibited the JMJD3-H3K27me3 interaction in mouse macrophage cells and down-regulated the expression of TNF-α. To our knowledge, complex 1 is the first metal-based inhibitor of JMJD3 activity and only the second class of JMJD3 inhibitor reported overall.

Adaptive evolution of mitochondrial genomes in Triplophysa cavefishes.

Extreme conditions in caves pose survival challenges for cave dwellers, who gradually develop adaptive survival features. Cavefishes are one of the most successful animals among cave dwellers. Triplophysa cavefishes are an important group of cavefishes, and they show remarkable adaptability to the extreme environments of caves. However, there is a limited understanding of their adaptation mechanisms. In this study, eight complete mitochondrial genomes of Triplophysa cavefishes were newly obtained, and their genomic characteristics, including the base composition, base bias, and codon usage, were analyzed. Phylogenetic analysis was carried out based on 13 mitochondrial protein-coding genes from 44 Nemacheilidae species. This showed that Triplophysa cavefishes and non-cavefishes separate into two reciprocally monophyletic clades, suggesting a single origin of the cave phenotype. Positive selection analysis strongly suggested that the selection pressure in cavefishes is higher than that in non-cavefishes. Furthermore, the ND5 gene in cavefishes showed evidence of positive selection, which suggests that the gene may play an important role in the adaptation of cavefishes to the cave environment. Protein structure analysis of the ND5 subunit implied that the sites of positive selection in cavefishes might allow them to acquire lower ND5 protein stability, compared to that in non-cavefishes, which might help the accumulation of nonsynonymous (mildly deleterious) mutations. Together, our study revealed the genetic signatures of cave adaptation in Triplophysa cavefishes from the perspective of energy metabolism.

All-Natural Plant-Derived Polyurethane as a Substitute of a Petroleum-Based Polymer Coating Material.

The development of efficient, biobased polyurethane controlled-release fertilizers from sustainable and eco-friendly biomaterials has received increased research attention, owing to concerns regarding global food security and environmental sustainability. Most previous studies focused on replacing petroleum-based polyols with biopolyols; however, the other main raw material, isocyanate, remained a petrochemical product. Herein, all-natural, plant-derived polyurethane-coated urea was successfully developed using castor oil and biobased isocyanate, and the performance of the coating shell before and after modification was compared. The results showed that the incorporation of a low dose of lauric acid copper into the coating material simultaneously enhanced the hydrophobicity and elasticity of the all-biobased polyurethane membrane, which prolonged the nitrogen release longevity from 3 to 112 days. In addition, the modified membrane showed excellent biodegradability in a soil environment. The novel all-biobased polyurethane coating material and modification technique provide insight for developing sustainable and eco-friendly controlled-release fertilizers.

Covered Stent Treatment for Direct Carotid-Cavernous Fistulas: A Meta-Analysis of Efficacy and Safety Outcomes.

BACKGROUND: Direct carotid-cavernous fistulas (dCCFs) involve the abnormal shunting of blood between the internal carotid artery and the cavernous sinus. The use of covered stents (CSs) has been reported for the treatment of complex carotid artery lesions. However, the efficacy and safety of CS treatment for dCCFs remain controversial. Thus, we performed a systematic review and meta-analysis to evaluate these efficacy and safety endpoints. METHODS: A systematic literature review was performed by comprehensively searching the Medline, Embase, and Web of Science databases to identify studies that were related to CS treatment for dCCFs. Then, a meta-analysis was conducted to pool the efficacy and safety outcomes from these studies based on perioperative and follow-up data. RESULTS: Fourteen noncomparative studies enrolling 156 patients with 160 dCCFs met the inclusion criteria. When analyzing perioperative outcomes, the technical success rate was 98.5% [95% confidence interval (CI), 0.948; 1.000], and the immediate complete occlusion rate was 90.9% (95% CI, 0.862; 0.959). Vasospasm and dissection occurred in 32.2% (95% CI, 0.238; 0.463) and 0.1% (95% CI, 0.000; 0.012) of patients, respectively. The in-stent acute thrombus formation rate was 0.1% (95% CI, 0.000; 0.013). Postoperatively, the mortality rate was 0.1% (95% CI, 0.000; 0.013). Based on available follow-up data, the final complete occlusion and parent artery stenosis rates were 99.3% (95% CI, 0.959; 1.000) and 18.6% (95% CI, 0.125; 0.277), respectively. CONCLUSIONS: CS placement can be used to safely and effectively treat dCCFs. These results provide a reference for future clinical trials.

Hollow cubic CuSe@CdS with tunable size for plasmon-induced Vis-NIR driven photocatalytic properties.

The rational design of the dimension and geometry of a plasmonic semiconductor cocatalyst is vitally important for efficient utilization of near-infrared (NIR) light and superior photocatalytic hydrogen generation. Herein, hollow cubic CuSe@CdS composites with different sizes and strong localized surface plasmon resonance (LSPR) were prepared by selenizing size-tunable Cu2O templates and loading CdS nanoparticles. The size of hollow cubic CuSe can affect the surface area and the conduction band potential through the size effect, regulating the carrier behavior of the CuSe@CdS heterojunction. The CuSe@CdS composites show enhanced and wide absorption in the full spectrum due to the LSPR effect of CuSe. Meanwhile, the composites show excellent photocatalytic hydrogen capacity in the full spectrum in a 0.35 M Na2S/0.25 M Na2SO3 sacrificial reagent solution. The best hydrogen production rate of CSCE2 is 1.518 mmol g-1 h-1 (5.54 times higher than that of CdS) under Vis light (780 > λ > 420 nm) irradiation and 0.28 mmol g-1 h-1 under NIR light (λ > 780 nm) illumination. Interestingly, the photocatalytic activity for H2 under Vis-NIR light (λ > 420 nm) is about 3 times (up to 4.45 mmol g-1 h-1) higher than that without NIR light assistance, due to the photothermal effect. Various analyses and DFT calculations demonstrate that the p-n heterojunction formed in the composites consists of p-type CuSe and n-type CdS, which achieves efficient carrier transfer and separation under the synergistic effect of the size effect and the photothermal effect. In addition, the expansion of the photocatalytic performance to the NIR range is mainly due to the "hot-electron" injection mechanism induced by the LSPR effect of CuSe. The reasonable design coupled with the plasmonic materials offers a new path to achieving the highly efficient conversion of solar energy to hydrogen energy.

Hydrogen exerts neuroprotective effects after subarachnoid hemorrhage by attenuating neuronal ferroptosis and inhibiting neuroinflammation.

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH), the third most common stroke subtype, is associated with high mortality and disability rates. Therefore, finding effective therapies to improve neurological function after SAH is critical. The objective of this study was to investigate the potential neuroprotective effects of hydrogen in the context of SAH, specifically, by examining its role in attenuating neuronal ferroptosis and inhibiting neuroinflammation, which are exacerbated by excess iron ions after SAH. METHODS: Mice were exposed to chambers containing 3% hydrogen, and cells were cultured in incubators containing 60% hydrogen. Neurological function in mice was assessed using behavioral scores. Protein changes were detected using western blotting. Inflammatory factors were detected using enzyme linked immunosorbent assay. Probes, electron microscopy, and related kits were employed to detect oxidative stress and ferroptosis. RESULTS: Hydrogen improved the motor function, sensory function, and cognitive ability of mice after SAH. Additionally, hydrogen facilitated Nuclear factor erythroid 2 -related factor 2 activation, upregulated Glutathione peroxidase 4, and inhibited Toll-like receptor 4, resulting in downregulation of inflammatory responses, attenuation of oxidative stress after SAH, and inhibition of neuronal ferroptosis. CONCLUSION: Hydrogen exerts neuroprotective effects by inhibiting neuronal ferroptosis and attenuating neuroinflammation after SAH.

Menaquinone-4 attenuates ferroptosis by upregulating DHODH through activation of SIRT1 after subarachnoid hemorrhage.

BACKGROUND: Menaquinone-4(MK-4), the isoform of vitamin K2 in the brain, exerts neuroprotective effects against a variety of central nervous system disorders. This study aimed to demonstrate the anti-ferroptosis effects of MK-4 in neurons after SAH. METHODS: A subarachnoid hemorrhage (SAH) model was prepared by endovascular perforation in mice. In vitro hemoglobin stimulation of primary cortical neurons mimicked SAH. MK-4, Brequinar (BQR, DHODH inhibitor), and Selisistat (SEL, SIRT1 inhibitor) were administered, respectively. Subsequently, WB, immunofluorescence was used to determine protein expression and localization, and transmission electron microscopy was used to observe neuronal mitochondrial structure while other indicators of ferroptosis were measured. RESULTS: MK-4 treatment significantly upregulated the protein levels of DHODH; decreased GSH, PTGS2, NOX1, ROS, and restored mitochondrial membrane potential. Meanwhile, MK-4 upregulated the expression of SIRT1 and promoted its entry into the nucleus. BQR or SEL partially abolished the protective effect of MK-4 on, neurologic function, and ferroptosis. CONCLUSIONS: Taken together, our results suggest that MK-4 attenuates ferroptosis after SAH by upregulating DHODH through the activation of SIRT1.

Paeoniflorin suppresses ferroptosis after traumatic brain injury by antagonizing P53 acetylation.

BACKGROUND: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown. PURPOSE: To investigate the mechanism by which Pae regulates ferroptosis after TBI. METHODS: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI. RESULTS: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53. CONCLUSION: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.

Integrated multi-omics reveal gut microbiota-mediated bile acid metabolism alteration regulating immunotherapy responses to anti-α4ß7-integrin in Crohn's disease.

Gut microbiota and related metabolites are both crucial factors that significantly influence how individuals with Crohn's disease respond to immunotherapy. However, little is known about the interplay among gut microbiota, metabolites, Crohn's disease, and the response to anti-α4ß7-integrin in current studies. Our research utilized 2,4,6-trinitrobenzene sulfonic acid to induce colitis based on the humanized immune system mouse model and employed a combination of whole-genome shotgun metagenomics and non-targeted metabolomics to investigate immunotherapy responses. Additionally, clinical cases with Crohn's disease initiating anti-α4ß7-integrin therapy were evaluated comprehensively. Particularly, 16S-rDNA gene high-throughput sequencing and targeted bile acid metabolomics were conducted at weeks 0, 14, and 54. We found that anti-α4ß7-integrin therapy has shown significant potential for mitigating disease phenotypes in remission-achieving colitis mice. Microbial profiles demonstrated that not only microbial composition but also microbially encoded metabolic pathways could predict immunotherapy responses. Metabonomic signatures revealed that bile acid metabolism alteration, especially elevated secondary bile acids, was a determinant of immunotherapy responses. Especially, the remission mice significantly enriched the proportion of the beneficial Lactobacillus and Clostridium genera, which were correlated with increased gastrointestinal levels of BAs involving lithocholic acid and deoxycholic acid. Moreover, most of the omics features observed in colitis mice were replicated in clinical cases. Notably, anti-α4ß7 integrin provided sustained therapeutic benefits in clinical remitters during follow-up, and long-lasting remission was linked to persistent changes in the microbial-related bile acids. In conclusion, gut microbiota-mediated bile acid metabolism alteration could play a crucial role in regulating immunotherapy responses to anti-α4ß7-integrin in Crohn's disease. Therefore, the identification of prognostic microbial signals facilitates the advancement of targeted probiotics that activate anti-inflammatory bile acid metabolic pathways, thereby improving immunotherapy responses. The integrated multi-omics established in our research provide valuable insights into potential mechanisms that impact treatment responses in complex diseases.