Causal links between gut microbiomes, cytokines and risk of different subtypes of epilepsy: a Mendelian randomization study.

Objective: Recent research suggests a potential link between the gut microbiome (GM) and epilepsy. We undertook a Mendelian randomization (MR) study to determine the possible causal influence of GM on epilepsy and its various subtypes, and explore whether cytokines act as mediators. Methods: We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM, cytokines, and four epilepsy subtypes. Furthermore, we assessed whether cytokines mediate the relationship between GM and epilepsy. Significant GMs were further investigated using transcriptomic MR analysis with genes mapped from the FUMA GWAS. Sensitivity analyses and reverse MR were conducted for validation, and false discovery rate (FDR) correction was applied for multiple comparisons. Results: We pinpointed causal relationships between 30 GMs and various epilepsy subtypes. Notably, the Family Veillonellaceae (OR:1.03, 95%CI:1.02-1.05, p = 0.0003) consistently showed a strong positive association with child absence epilepsy, and this causal association endured even after FDR correction (p-FDR < 0.05). Seven cytokines were significantly associated with epilepsy and its subtypes. A mediating role for cytokines has not been demonstrated. Sensitivity tests validated the primary MR analysis outcomes. Additionally, no reverse causality was detected between significant GMs and epilepsy. Of the mapped genes of notable GMs, genes like BLK, FDFT1, DOK2, FAM167A, ZSCAN9, RNGTT, RBM47, DNAJC21, SUMF1, TCF20, GLO1, TMTC1, VAV2, and RNF14 exhibited a profound correlation with the risk factors of epilepsy subtypes. Conclusion: Our research validates the causal role of GMs and cytokines in various epilepsy subtypes, and there has been no evidence that cytokines play a mediating role between GM and epilepsy. This could provide fresh perspectives for the prevention and treatment of epilepsy.

Metabolome-Wide Mendelian Randomization Assessing the Causal Role of Serum and Cerebrospinal Metabolites in Traumatic Brain Injury.

Previous studies have identified metabolites as biomarkers or potential therapeutic targets for traumatic brain injury (TBI). However, the causal association between them remains unknown. Therefore, we investigated the causal effect of serum metabolites and cerebrospinal fluid (CSF) metabolites on TBI susceptibility through Mendelian randomization (MR). Genetic variants related to metabolites and TBI were extracted from a corresponding genome-wide association study (GWAS). Causal effects were estimated through the inverse variance weighted approach, supplemented by a weighted median, weight mode, and the MR-Egger test. In addition, sensitivity analyses were further performed to evaluate the stability of the MR results, including the MR-Egger intercept, leave-one-out analysis, Cochrane's Q-test, and the MR-PRESSO global test. Metabolic pathway analysis was applied to uncover the underlying pathways of the significant metabolites in TBI. In blood metabolites, substances such as 4-acetaminophen sulfate and kynurenine showed positive links, whereas beta-hydroxyisovalerate and creatinine exhibited negative correlations. CSF metabolites such as N-formylanthranilic acid were positively related, while kynurenate showed negative associations. The metabolic pathway analysis highlighted the potential biological pathways involved in TBI. Of these 16 serum metabolites, 11 CSF metabolites and metabolic pathways may serve as useful circulating biomarkers in clinical screening and prevention, and may be candidate molecules for the exploration of mechanisms and drug targets.

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study.

Background: Previous studies suggests that gut microbiomes are associated with the formation and progression of aneurysms. However, the causal association between them remains unclear. Methods: A two-sample Mendelian randomization was conducted to investigate whether gut microbiomes have a causal effect on the risk of intracerebral aneurysm (IA), thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), and aortic aneurysm (AA). Single nucleotide polymorphisms (SNPs) smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. We used inverse-variance weighted (IVW) test as the primary method for the evaluation of causal association. MR-Egger, weighted median, weighted mode, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods were conducted for sensitive analysis. The p-value was adjusted by the false discovery rate (FDR) which adjust the results of multiple comparisons, a p < 0.05 and q < 0.1 was considered a significant causal association. Additionally, a p < 0.05 and q > 0.1 was considered a suggestive causal effect. Additionally, reverse MR was also performed to exclude the possibility of reverse causality. Results: The phylum Firmicutes (OR = 0.62; 95% CI, 0.48-0.81), class Lentisphaeria (OR = 0.75; 95% CI, 0.62-0.89), and order Victivallales (OR = 0.75; 95% CI, 0.62-0.89) have a causal protective effect on the risk of AAA. Additionally, class Verrucomicrobia, class Deltaproteobacteria, order Verrucomicrobiale, family Verrucomicrobiacea, genus Eubacterium rectale group, genus Akkermansia, and genus Clostridium innocuum group were negatively associated with the risk of different types of aneurysms, whereas class Negativicutes, order Selenomonadales, and genus Roseburia had positive causal association with different types of aneurysms (p < 0.05; q > 0.1). Further sensitivity analysis validated the robustness of our MR results, and no reverse causality was found with these gut microbiomes (p > 0.05). Conclusion: Our MR analysis confirmed the causal association of specific gut microbiomes with AAA, and these microbiomes were considered as protective factors. Our result may provide novel insights and theoretical basis for the prevention of aneurysms through regulation of gut microbiomes.

Adjunctive cariprazine as a novel effective strategy for treating major depressive disorder: A systematic review and meta-analysis.

BACKGROUND: Cariprazine has been approved by the Food and Drug Administration for treating bipolar depression and as an adjunctive treatment for Major Depressive Disorder (MDD). However, it remains unclear about its pharmacological efficacy in treating MDD. Therefore, a meta-analysis was conducted to investigate the adjunctive use of cariprazine in MDD. METHODS: Electronic databases were searched for eligible studies evaluating the efficacy and safety of cariprazine in patients with MDD up to November 15, 2023. The changes in Montgomery-Asberg Depression Rating Scale (MADRS) score and incidence of adverse events (AEs), which represents of efficacy and tolerability, are considered as the main outcomes. RESULTS: A total of 3066 patients with MDD included in all across 5 RCTs. With regard to MADRS score, cariprazine group showed better results than control group (SMD = -0.12, 95% CI -0.19 to -0.04, P = 0.002, 5 RCTs, n = 3066). Cariprazine, meanwhile, improved the MADRS response (RR = 1.19, 95% CI 1.08 to 1.31, P = 0.0004, 5 RCTs, n = 3066). For safety outcomes, statistical difference was observed in AEs (RR = 1.26, 95% CI 1.18 to 1.35, P < 0.00001, 5 RCTs, n = 3077). The suicide ideation and SAEs showed no statistical difference between two groups. CONCLUSION: Cariprazine demonstrated antidepressant effect as an augmentation therapy in treating MDD. Meanwhile, the tolerability of it was acceptable as an adjunctive treatment. However, studies with larger sample sizes are still needed to explore the optimal dosage.

Therapeutic inertia in treatment of older adults with type II diabetes at high risk for hypoglycemia.

Patients 80 years or older with HbA1c <7.0% (53 mmol/mol) treated with multiple daily insulin injections had low rates of rapid-acting insulin deprescription and initiation of diabetes medications with lower risk of hypoglycemia. Further investigation is needed to elucidate factors contributing to potentially inappropriately aggressive treatment of these patients.

Causal association of leisure sedentary behavior and cervical spondylosis, sciatica, intervertebral disk disorders, and low back pain: a Mendelian randomization study.

Background: Some studies suggest sedentary behavior is a risk factor for musculoskeletal disorders. This study aimed to investigate the potential causal association between leisure sedentary behavior (LSB) (including television (TV) viewing, computer use, and driving) and the incidence of sciatica, intervertebral disk degeneration (IVDD), low back pain (LBP), and cervical spondylosis (CS). Methods: We obtained the data of LSB, CS, IVDD, LBP, sciatica and proposed mediators from the gene-wide association studies (GWAS). The causal effects were examined by Inverse Variance Weighted (IVW) test, MR-Egger, weighted median, weighted mode and simple mode. And sensitivity analysis was performed using MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and MR-Egger intercept test. Multivariable MR (MVMR) was conducted to investigate the independent factor of other LSB; while two-step MR analysis was used to explore the potential mediators including Body mass index (BMI), smoking initiation, type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), schizophrenia, bipolar disorder between the causal association of LSB and these diseases based on previous studies. Results: Genetically associated TV viewing was positively associated with the risk of CS (OR = 1.61, 95%CI = 1.25 to 2.07, p = 0.002), IVDD (OR = 2.10, 95%CI = 1.77 to 2.48, p = 3.79 × 10-18), LBP (OR = 1.84, 95%CI = 1.53 to 2.21, p = 1.04 × 10-10) and sciatica (OR = 1.82, 95% CI = 1.45 to 2.27, p = 1.42 × 10-7). While computer use was associated with a reduced risk of IVDD (OR = 0.66, 95%CI = 0.55 to 0.79, p = 8.06 × 10-6), LBP (OR = 0.49, 95%CI = 0.40 to 0.59, p = 2.68 × 10-13) and sciatica (OR = 0.58, 95%CI = 0.46 to 0.75, p = 1.98 × 10-5). Sensitivity analysis validated the robustness of MR outcomes. MVMR analysis showed that the causal effect of TV viewing on IVDD (OR = 1.59, 95%CI = 1.13 to 2.25, p = 0.008), LBP (OR = 2.15, 95%CI = 1.50 to 3.08, p = 3.38 × 10-5), and sciatica (OR = 1.61, 95%CI = 1.03 to 2.52, p = 0.037) was independent of other LSB. Furthermore, two-step MR analysis indicated that BMI, smoking initiation, T2DM may mediate the causal effect of TV viewing on these diseases. Conclusion: This study provides empirical evidence supporting a positive causal association between TV viewing and sciatica, IVDD and LBP, which were potentially mediated by BMI, smoking initiation and T2DM.

The efficacy and tolerability of inhaled nitrous oxide in major depressive disorder: a systematic review and meta-analysis.

BACKGROUND: Nitrous oxide (N2O) has been initially confirmed by clinical trials to benefit to patients with major depressive disorder (MDD). However, there needs to be a meta-analysis to compare the efficacy and tolerability of N2O in MDD. METHODS: PubMed, EMBASE, and Cochrane Library were searched for relevant studies up to Jan 1st, 2023. The meta-analysis mainly compared the outcome of the change in depression severity scores, response, remission, and adverse events in patients with MDD receiving 50% N2O and placebo. RESULTS: Four studies with 133 patients were eventually identified. We found that the N2O group and control group showed an overall significant difference in the change in depression severity score for patients at 2 h, 24 h, and 2 weeks or more (2 h, SMD = - 0.64, 95% CI - 0.01 to - 0.28, p < 0.0001) (24 h, SMD = - 0.65, 95% CI - 1.01 to - 0.29, p < 0.0001) (2 weeks, SMD = - 0.76, 95% CI - 1.16 to - 0.36, p < 0.0001). For the response and remission rate, the long-term effect of N2O was also statistically significant (for the response, RR = 2.33, 95% CI 1.23 to 4.44, p = 0.01) (for the remission, RR = 4.68, 95% CI 1.49 to 14.68, p = 0.008). For safety outcomes, patients treated with N2O had higher odds of nausea or vomiting (RR = 10.15, 95% CI 1.96 to 52.59, p = 0.009). CONCLUSION: Our study suggested that N2O has a rapid and long-lasting antidepressant effect in patients with MDD. However, the efficacy of lower or titrated concentration of N2O should be further investigated.

Motor function improvement and acceptability of non-invasive brain stimulation in patients with Parkinson's disease: a Bayesian network analysis.

Background: Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive motor and non-motor symptoms. Currently, the pro-cognitive effects of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are well-supported in previous literatures. However, controversy surrounding the optimal therapeutic target for motor symptom improvement remains. Objective: This network meta-analysis (NMA) was conducted to comprehensively evaluate the optimal strategy to use rTMS and tDCS to improve motor symptoms in PD. Methods: We searched PubMed, Embase, and Cochrane electronic databases for eligible randomized controlled studies (RCTs). The primary outcome was the changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, the secondary outcomes were Time Up and Go Test (TUGT) time, and Freezing of Gait Questionnaire (FOGQ) score. The safety outcome was indicated by device-related adverse events (AEs). Result: We enrolled 28 studies that investigated various strategies, including high-frequency rTMS (HFrTMS), low-frequency rTMS (LFrTMS), anodal tDCS (AtDCS), AtDCS_ cathode tDCS (CtDCS), HFrTMS_LFrTMS, and Sham control groups. Both HFrTMS (short-term: mean difference (MD) -5.21, 95% credible interval (CrI) -9.26 to -1.23, long-term: MD -4.74, 95% CrI -6.45 to -3.05), and LFrTMS (long-term: MD -4.83, 95% CrI -6.42 to -3.26) were effective in improving UPDRS-III score compared with Sham stimulation. For TUGT time, HFrTMS (short-term: MD -2.04, 95% CrI -3.26 to -0.8, long-term: MD -2.66, 95% CrI -3.55 to -1.77), and AtDCS (short-term: MD -0.8, 95% CrI -1.26 to -0.34, long-term: MD -0.69, 95% CrI -1.31 to -0.08) produced a significant difference compared to Sham stimulation. However, no statistical difference was found in FOGQ score among the various groups. According to the surface under curve ranking area, HFrTMS ranked first in short-term UPDRS-III score (0.77), short-term (0.82), and long-term (0.84) TUGT time, and short-term FOGQ score (0.73). With respect to the safety outcomes, all strategies indicated few and self-limiting AEs. Conclusion: HFrTMS may be the optimal non-invasive brain stimulation (NIBS) intervention to improve motor function in patients with PD while NIBS has generally been well tolerated. However, further studies focusing on the clinical outcomes resulting from the different combined schedules of tDCS and rTMS are required. Systematic review registration: https://inplasy.com/inplasy-2023-4-0087/, identifier: 202340087.

Comparison of different surgical techniques for chronic subdural hematoma: a network meta-analysis.

Background: Chronic subdural hematoma (CSDH) is a neurosurgical condition with high prevalence. Many surgical approaches are recommended for treating CSDH, but there needs to be a consensus on the optimal technique. This network meta-analysis (NMA) compared the efficacy and safety of different surgical treatments for CSDH. Methods: Electronic databases, including PubMed, Embase, and the Cochrane Library, were searched for relevant studies up to February 2023. An NMA was performed to compare the outcomes of patients with CSDH treated by single-hole or double-hole craniotomy (SBHC and DBHC, respectively), twist-drill craniotomy (TDC), mini-craniotomy, and craniotomy. The NMA protocol was registered at INPLASY (registration no. 202320114). Results: The NMA included 38 studies with 7,337 patients. For efficacy outcomes, DBHC showed the highest surface under the cumulative ranking area (SUCRA) values for recurrence (96.3%) and reoperation (87.4%) rates. DBHC differed significantly from mini-craniotomy in recurrence rate (odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.35, 0.97) and from SBHC (OR = 0.48, 95% CI: 0.25, 0.91) and TDC (OR = 0.40, 95% CI: 0.20, 0.82) in reoperation rate. For operative time, TDC was superior to SBHC (mean difference [MD] = -2.32, 95% CI: -3.78 to -0.86), DBHC (MD = -3.61, 95% CI: -5.55, -1.67), and mini-craniotomy (MD = -3.39, 95% CI: -5.70, -1.08). Patients treated by TDC had a shorter hospital stay than those treated by SBHC (MD = -0.82, 95% CI: -1.51, -0.12). For safety outcomes, there were no significant differences between groups in mortality and complication rates; however, mini-craniotomy (79.8%) and TDC (78.1%) had the highest SUCRAs. Conclusion: DBHC may be the most effective surgical treatment for CSDH based on the low recurrence and reoperation rates, although all examined techniques were relatively safe. Systematic review registration: https://inplasy.com/inplasy-2023-2-0114/.

Early versus late tracheostomy in stroke-related patients: A systematic review and meta-analysis.

BACKGROUND: Tracheostomy is an operative intervention for patients who require ventilator assistance while in the intensive care unit (ICU). This study aimed to compare efficacy and safety between early tracheostomy (ET) and late tracheostomy (LT) in stroke patients. METHODS: Embase, PubMed, and the Cochrane Library were searched for available studies. Stroke-related patients were categorized into ET and LT groups using seven days as the cutoff timepoint. The primary efficacy outcome was mortality; secondary efficacy outcomes were modified Rankin Scores (mRS) obtained at follow up, as well as durations of hospital stay, ICU stay, and ventilator use. Safety outcomes were total complication and ventilator associated pneumonia (VAP) incidence. RESULTS: Nine studies with 3,789 patients were included in the current analysis. No statistical difference in mortality was observed. ET was associated with shorter hospital stay (MD -5.72, 95% CI -9.76 to -1.67), shorter ICU stay (MD -4.77, 95% CI -6.82 to -2.72), and shorter ventilator duration (MD -4.65, 95% CI -8.39 to -0.90); however, no statistically significant difference was found in follow-up mRS scores. Examination of safety measures found the ET group exhibited a lower rate of VAP compared with LT (OR 0.80, 95 % CI 0.68 to 0.93), while no statistical difference was found in total complications. CONCLUSION: Our meta-analysis concluded that ET was associated with shorter hospital stay, less time on a ventilator, and lower incidence of VAP. Future studies are warranted to investigate the functional outcomes and the occurrence of complications of ET in stroke patients.

Efficacy and tolerability of minocycline in depressive patients with or without treatment-resistant: a meta-analysis of randomized controlled trials.

Background: Minocycline, an antibiotic with anti-inflammatory, antioxidant, and neuroprotective properties, has been used for treating psychiatric disorders in research. This systematic review aimed to evaluate the efficacy and tolerability of minocycline in patients having depression with or without treatment-resistance. Methods: Electronic databases including Embase, PubMed, and the Cochrane library were searched for relevant studies published up to October 17, 2022. The primary efficacy outcome was the change in depression severity scores and the secondary efficacy outcomes included the changes in Clinical Global Impression (CGI) and Beck Depression Inventory (BDI) scores and the incidence of response and partial response. Safety outcomes were evaluated based on the incidence of classified adverse events and all-cause discontinuation. Results: Five studies with 374 patients were selected for analysis. The minocycline group demonstrated a significant reduction in depression severity scale (standardized mean difference [SMD]: -0.59, 95% confidence interval [CI]: -0.98 to -0.20, P = 0.003) and CGI (SMD: -0.28, 95% CI: -0.56 to -0.01, P = 0.042) scores; however, no statistical difference was found in terms of the BDI score, response, and partial response. No significant differences were found between the groups in terms of adverse events (other than dizziness) and discontinuation rates. Subgroup analysis showed that minocycline was also effective in reducing depression severity scores in treatment-resistant depression (SMD: -0.36, 95% CI: -0.64 to -0.09, P = 0.010). Subgroup analysis of Hamilton Depression Rating Scale (17-item) scores showed a statistical difference in response in patients with depression (relative risk: 2.51, 95% CI: 1.13 to 5.57, P = 0.024). Conclusions: Minocycline may improve depressive symptoms and augment response to treatment in patients with depression irrespective of treatment-resistance. However, clinical trials with large sample sizes are warranted for evaluating long-term outcomes with minocycline. Systematic review registration: https://inplasy.com/inplasy-2022-12-0051/.

An Assessment of the Pathological Classification and Postoperative Outcome of Focal Cortical Dysplasia by Simultaneous Hybrid PET/MRI.

OBJECTIVES: The purpose of this research was to investigate whether MRI and Simultaneous Hybrid PET/MRI images were consistent in the histological classification of patients with focal cortical dysplasia. Additionally, this research aimed to evaluate the postoperative outcomes with the MRI and Simultaneous Hybrid PET/MRI images of focal cortical dysplasia. METHODS: A total of 69 cases in this research were evaluated preoperatively for drug-resistant seizures, and then surgical resection procedures of the epileptogenic foci were performed. The postoperative result was histopathologically confirmed as focal cortical dysplasia, and patients then underwent PET and MRI imaging within one month of the seizure. In this study, head MRI was performed using a 3.0 T magnetic resonance scanner (Philips) to obtain 3D T1WI images. The Siemens Biograph 16 scanner was used for a routine scanning of the head to obtain PET images. BrainLAB's iPlan software was used to fuse 3D T1 images with PET images to obtain PET/MRI images. RESULTS: Focal cortical dysplasia was divided into three types according to ILAE: three patients were classified as type I, twenty-five patients as type II, and forty-one patients as type III. Patients age of onset under 18 and age of operation over 18 had a longer duration (p = 0.036, p = 0.021). MRI had a high lesion detection sensitivity of type III focal cortical dysplasia (p = 0.003). Simultaneous Hybrid PET/MRI showed high sensitivity in detecting type II and III focal cortical dysplasia lesions (p = 0.037). The lesions in Simultaneous Hybrid PET/MRI-positive focal cortical dysplasia patients were mostly located in the temporal and multilobar (p = 0.005, 0.040). CONCLUSION: Simultaneous Hybrid PET/MRI has a high accuracy in detecting the classification of focal cortical dysplasia. The results of this study indicate that patients with focal cortical dysplasia with positive Simultaneous Hybrid PET/MRI have better postoperative prognoses.

Efficacy and tolerability of zuranolone in patients with depression: a meta-analysis of randomized controlled trials.

Background: As a novel antidepressant drug, zuranolone has been initially applied in treating depression. This study investigated the efficacy and safety of its administration in patients with depression. Methods: The Embase, PubMed, and Cochrane library databases were searched for available studies up to 1 Nov 2023. The primary outcome was the change on day 15 depression severity scores compared to baseline. Secondary outcomes included remission and response rates on day 15. Safety outcomes included incidence of treatment-emergent adverse events (TEAEs) and individual AEs. Trial sequential analysis (TSA) was used to evaluate the ideal samplesize. Results: Six studies with 1884 patients were included. Zuranolone offered significantly greater changes in day 15 depression severity scores (mean difference = 2.43, 95% confidence interval [CI]: 1.36 to 3.49, p < 0.00001) compared to placebo; this was also observed at other time points. Differences in response (relative risk [RR] = 1.33, 95% CI: 1.15 to 1.54, p < 0.0001) and remission (RR = 1.46, 95% CI: 1.15 to 1.85, p = 0.002) rates were also statistically significant. For safety outcomes, zuranolone group showed more incidence of TEAE than the placebo group (RR: 1.15, 95% CI: 1.06 to 1.25, p = 0.0005, I 2 = 0%). As for individual AEs, significant differences were observed in dizziness (RR = 2.17, 95% CI: 1.22 to 3.86, p = 0.008) and somnolence (RR = 2.43, 95% CI: 1.35 to 4.37, p = 0.003. No significant difference was observed in other AEs. The result of TSA indicated that the cumulative curve crossed the conventional (Z = 1.96) boundary but not reach TSA boundary (RIS = 1910). Conclusion: Our findings suggest that zuranolone has a rapid short-term antidepressant effect during administration. Although more TEAEs were observed in zuranolone, most of them were slight and temporary. However, studies with larger sample sizes and longer follow-up are needed. Systematic Review Registration: https://inplasy.com/inplasy-2023-5-0104/, identifier INPLASY202350104.

Physiological function and regulatory signal of intestinal type 3 innate lymphoid cell(s).

Of the three groups of innate lymphoid cells, the type 3 innate lymphoid cell(s) (ILC3) include the subgroup of enteric ILC3 that participates in many physiological functions of the organism, such as promoting the repair of damaged mucosa, maintaining the homeostasis of gut symbiotic microorganisms, and presenting specific antigens. ILC3 also includes splenic and decidual ILC3. Like other physiological processes in the organism, enteric ILC3 functions are precisely regulated at the endogenous and exogenous levels. However, there has been no review on the physiological functions and regulatory signals of intestinal ILC3. In this paper, based on the current research on the physiological functions of enteric ILC3 in animals and the human, we summarize the signals that regulate cytokine secretion, antigen presentation and the quantity of ILC3 under normal intestinal conditions. We discuss for the first time the classification of the promoting mechanism of secretagogues of ILC3 into direct and indirect types. We also propose that ILC3 can promote intestinal homeostasis, and intestinal homeostasis can ensure the physiological phenotype of ILC3. If homeostasis is disturbed, ILC3 may participate in intestinal pathological changes. Therefore, regulating ILC3 and maintaining intestinal homeostasis are critical to the body.