Atg5 deficiency in macrophages protects against kidney fibrosis via the CCR6-CCL20 axis.

BACKGROUND: Autophagy is a lysosome-dependent degradation pathway that regulates macrophage activation, differentiation, and polarization. Autophagy related 5 (Atg5) is a key protein involved in phagocytic membrane elongation in autophagic vesicles that forms a complex with Atg12 and Atg16L1. Alterations in Atg5 are related to both acute and chronic kidney diseases in experimental models. However, the role of macrophage-expressed Atg5 in acute kidney injury remains unclear. METHODS: Using a myeloid cell-specific Atg5 knockout (MΦ atg5-/-) mouse, we established renal ischemia/reperfusion and unilateral ureteral obstruction models to evaluate the role of macrophage Atg5 in renal macrophage migration and fibrosis. RESULTS: Based on changes in the serum urea nitrogen and creatinine levels, Atg5 deletion had a minimal effect on renal function in the early stages after mild injury; however, MΦ atg5-/- mice had reduced renal fibrosis and reduced macrophage recruitment after 4 weeks of ischemia/reperfusion injury and 2 weeks of unilateral ureteral obstruction injury. Atg5 deficiency impaired the CCL20-CCR6 axis after severe ischemic kidneys. Chemotactic responses of bone marrow-derived monocytes (BMDMs) from MΦ atg5-/- mice to CCL20 were significantly attenuated compared with those of wild-type BMDMs, and this might be caused by the inhibition of PI3K, AKT, and ERK1/2 activation. CONCLUSIONS: Our data indicate that Atg5 deficiency decreased macrophage migration by impairing the CCL20-CCR6 axis and inhibited M2 polarization, thereby improving kidney fibrosis.

Hydrothermal treatment improves xanthine oxidase inhibitory activity and affects the polyphenol profile of Flos Sophorae Immaturus.

BACKGROUND: Flos Sophorae Immaturus (FSI) is rich in polyphenols and a potential uric acid-lowering food. However, the processing of FSI is greatly restricted due to the heat sensitivity and low solubility of polyphenols. In this study, hydrothermal treatment - an effective strategy - was applied to FSI processing. The variation of xanthine oxidase (XO) inhibitory effect and polyphenol composition of FSI during hydrothermal treatment were recorded. RESULTS: The XO inhibition rate of FSI increased from 32.42% to 89.00% after hydrothermal treatment at 220 °C for 30 min, as well as total polyphenols (from 0.66 to 1.11 mg mL-1 ) and flavonoids (from 1.21 to 1.58 mg mL-1 ). However, high thermal temperature (>160 °C) and extended thermal time (>90 min) caused the degradation of polyphenols. Rutin, kaempferol-3-O-rutinoside and narcissoside rapidly degraded and converted to quercetin, kaempferol and isorhamnetin when the temperature exceeded 160 °C. The maximum yields of quercetin, kaempferol and isorhamnetin were at 220 °C for 30 min, 90 min and 90 min, respectively. Meanwhile, the conversion kinetics conformed to the first-order model. Interestingly, these newly formed polyphenols possessed better XO inhibitory effects than their derivatives with 3-O-rutinoside. CONCLUSION: Polyphenol conversion during hydrothermal treatment was the main reason for enhancing XO inhibitory activity. Therefore, hydrothermal treatment is an appropriate method for improving the XO inhibitory effect of FSI. © 2022 Society of Chemical Industry.

Sodium butyrate exerts antioxidant stress effects and attenuates Aß25-35-induced cytotoxicity in PC12 cells.

Alzheimer's disease (AD), a common neurodegenerative disease, is characterised by the deposition of amyloid-ß (Aß) plaques and neurofibrillary tangles. An increasing number of studies have demonstrated that Aß causes neuronal damage and mitochondrial dysfunction. Herein, we evaluated the neuroprotective effect of sodium butyrate (NaB) against Aß induced neurotoxicity in PC12 cells. The results revealed that 3 mM of NaB promoted the expression of angiotensin-converting enzyme and brain-derived neurotrophic factor, which exert a neuroprotective effect by activating G protein-coupled receptors. Moreover, NaB could significantly improve mitochondrial dysfunction caused by Aß. In conclusion, NaB protected PC12 cells from Aß-induced cell damage, highlighting the potential of NaB in AD treatment.

Nutritional Attributes and Phenolic Composition of Flower and Bud of Sophora japonica L. and Robinia pseudoacacia L.

Sophora japonica L. (SJL) and Robinia pseudoacacia L. (RPL) are widely cultivated in China. However, the utilization of their main by-products are limited due to a lack of comprehensive nutritional attributes. Herein, the proximate composition, mineral elements, fatty acids, amino acids, monosaccharides, and phenolics were analyzed to investigate the nutritional attributes of SJL and RPL. Dietary fiber was the main ingredient in SJL and RPL, followed by protein and lipids. The content of Fe in SJL and RPL was highest, especially in flowers of SJL, reaching about 1179.51 mg/kg. The total unsaturated fatty acids accounted for 89.67% of the bud of SJL. Meanwhile, the essential amino acids contents of the flower and bud of SJL and RPL accounted for 35.95-40.59% of total amino acids. The flower of SJL (373.75 mg/g) exhibited the most abundant monosaccharides. Meanwhile, the total phenolics and flavonoid contents in the buds of SJL and RPL were significantly higher than that of the flower, implying the buds possessed better biological activity. Moreover, the bud of SJL possessed the most abundant phenolics. The results provided a reference for the development of functional food derived from SJL and RPL.

BHBA treatment improves cognitive function by targeting pleiotropic mechanisms in transgenic mouse model of Alzheimer's disease.

Accumulation of amyloid ß (Aß) peptide, inflammation, and oxidative stress contribute to Alzheimer's disease (AD) and trigger complex pathogenesis. The ketone body ß-hydroxybutyrate (BHBA) is an endogenous metabolic intermediate that protects against stroke and neurodegenerative diseases, but the underlying mechanisms are unclear. The present study aims to elucidate the protective effects of BHBA in the early stage of AD model and investigate the underlying molecular mechanisms. Three-and-half-month-old double-transgenic mice (5XFAD) overexpressing ß-amyloid precursor protein (APP) and presenilin-1 (PS1) were used as the AD model. The 5XFAD mice received 1.5 mmol/kg/d BHBA subcutaneously for 28 days. Morris water maze test, nest construction, and passive avoidance experiments were performed to assess the therapeutic effects on AD prevention in vivo, and brain pathology of 5XFAD mice including amyloid plaque deposition and microglia activation were assessed. Gene expression profiles in the cortexes of 5XFAD- and BHBA-treated 5XFAD mice were performed with high-throughput sequencing and bioinformatic analysis. Mouse HT22 cells were treated with 2 mM BHBA to explore its in vitro protective effects of BHBA on hippocampal neurons against Aß oligomer toxicity, ATP production, ROS generation, and mitochondrial aerobic respiratory function. APP, BACE1, and neprilysin (NEP) expression levels were evaluated in HT22 cells following treatment with BHBA by measuring the presence or absence of G protein-coupled receptor 109A (GPR109A). BHBA improved cognitive function of 5XFAD mice in Morris water maze test, nesting construction and passive avoidance experiments, and attenuated Aß accumulation and microglia overactivation in the brain. BHBA also enhanced mitochondrial respiratory function of hippocampal neurons and protected it from Aß toxicity. The enzymes, APP and NEP were regulated by BHBA via G-protein-coupled receptor 109A (GPR109A). Furthermore, RNA sequencing revealed that BHBA-regulated genes mainly annotated in aging, immune system, nervous system, and neurodegenerative diseases. Our data suggested that BHBA confers protection against the AD-like pathological events in the AD mouse model by targeting multiple aspects of AD and it may become a promising candidate for the prevention and treatment of AD.

[Genetic analysis of three patients with Kleefstra syndrome].

OBJECTIVE: To analyze the clinical and genetic features of three patient diagnosed with Kleefstra syndrome. METHODS: Whole exome sequencing (WES) was carried out for the probands and their parents. Suspected variants were validated by Sanger sequencing. Copy number variations (CNV) were detected by CNV-seq and validated by real-time PCR. RESULTS: Proband 1 was found to carry a de novo heterogeneous variant (c.823+1G>T) of the EHMT1 gene, which may affect its expression. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS2+PM2). Proband 2 was found to carry a de novo missense variant c.439C>G (p.L147V) of the EHMT1 gene, which was predicted to be likely pathogenic (PS2+PM1+PM2+PP3). Proband 3 was found to carry a heterozygous 520 kb deletion at 9q34.3 by CNV-seq. The deletion has encompassed the whole of the EHMT1 gene. Real-time PCR has detected no CNV of this region in her parents. CONCLUSION: Variants of the EHMT1 gene probably underlay the disease in these patients. Genetic testing has provided a basis for their clinical diagnosis.

Sodium Butyrate Protects N2a Cells against Aß Toxicity In Vitro.

Alzheimer's disease (AD) is a common neurodegenerative disease. Aß plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against Aß toxicity and to uncover the underlying mechanisms. The results showed that 2 mM NaB had a significant improvement effect on Aß-induced N2a cell injury, by increasing cell viability and reducing ROS to reduce injury. In addition, by acting on the GPR109A receptor, NaB regulates the expression of AD-related genes such as APP, NEP, and BDNF. Therefore, NaB protects N2a cells from Aß-induced cell damage through activating GPR109A, which provides an innovative idea for the treatment of AD.

[Clinical and genetic analysis of four patients with congenital neutropenia].

OBJECTIVE: To delineate the clinical feature and genetic basis of four patients with congenital neutropenia. METHODS: All patients were subjected to whole exome sequencing (WES). Suspected variants were verified by Sanger sequencing. RESULTS: The patients (two boys and two girls), aged 7 to 15 months, suffered from neutropenia and recurrent infections. Bone marrow smears showed a significant decrease in the proportion of rod-shaped and lobulated granulocytes, which suggested impaired development and maturation of bone marrow neutrophils. WES has discovered heterozygous variants (c.496G>A, c.58C>G, c.391G>A and IVS1+5T>A) of the ELANE gene in the patients. Among these, c.58C>G and IVS1+5T>A were unreported previously. Follow up revealed patients 1 and 3 had periodic neutropenia, while patients 2 and 4 had severe congenital neutropenia. After attaining the definite diagnosis, the patients were treated symptomatically. CONCLUSION: The main clinical feature of congenital neutropenia is refractory recurrent bacterial infections, for which mutations of the ELANE gene are a common cause. Two novel pathogenic ELANE variants have been discovered in this study.

[Clinical manifestations and genetic diagnosis of paroxysmal kinesigenic dyskinesia].

The clinical manifestations of five children with paroxysmal kinesigenic dyskinesia (PKD) were retrospectively analyzed and their gene mutations were analyzed by high-throughput sequencing and chromosome microarray. The 5 patients consisted of 4 males and 1 female and the age of onset was 6-9 years. Dyskinesia was induced by sudden turn movement, scare, mental stress, or other factors. These patients were conscious and had abnormal posture of unilateral or bilateral extremities, athetosis, facial muscle twitching, and abnormal body posture. The frequency of onset ranged from 3-5 times a month to 2-7 times a day, with a duration of <30 seconds every time. Electroencephalography showed no abnormality in these patients. Three patients had a family history of similar disease. The high-throughput sequencing results showed that a heterozygous mutation in the PRRT2 gene, c.649_650insC (p.R217PfsX8), was found in two patients; the mutation c.436C>T (p.P146S) was found in one patient; a splice site mutation, IVS2-1G>A, was found in one patient. The two mutations c.436C>T and IVS2-1G>A had not been reported previously. The chromosome microarray analysis was performed in one patient with negative results of gene detection, and the chromosome 16p11.2 deletion (0.55 Mb) was observed. Low-dose carbamazepine was effective for treatment of the 5 patients. PKD is a rare neurological disease. The detection of the PRRT2 gene by multiple genetic analysis can help the early diagnosis of PKD.

[Study on ecological suitability of Gardenia jasminoides based on ArcGIS and Maxent model].

The application of ArcGIS and Maxent modelto analyze the ecological suitability of Gardenia jasminoides.Taking 85 batches of Gardenia as the basis of analysis, the selection of ecological factors for the growth of Gardenia. The results showed that the average precipitation in April, the average precipitation in November and the average precipitation in August were the most important factors affecting the growth of Gardenia. The relative concentration of Gardenia suitable growth region,north to the south of Shaanxi province, south of Henan, central Anhui, south to the north of Hainan province, west to central Sichuan province, east of Zhejiang coastal area, northeast of Taiwan.

[Clinical applications of rigid bronchoscopy in central airway obstructions].

OBJECTIVE: Rigid bronchoscopy has expanded for therapeutic purposes lately. It has a large diameter working channel, the ability to maintain proper ventilation during operation, and the capacity to deal with massive bleeding and other complications. Our purpose was to describe the effectiveness and safety of rigid bronchoscopy in central airway stenosis. METHODS: We retrospectively analyzed all patients who had received rigid bronchoscopy for central airway obstruction in our respiratory department of this teaching hospital between December of 2008 and December of 2014. The advantages and limitations of the operations were analyzed through observing the changes of the degree of stenosis, pulmonary function, and Karnofsky performance status scale. Complications were also recorded. RESULTS: Totally 209 rigid bronchoscopic procedures were performed in 132 patients with central airway stenosis (86 men; median age, 59 years; range, 9 to 85 years), of them 68% was malignancy. The rigid bronchoscopy provided immediate relief of central airway obstruction. Tracheal obstruction was (63.3 ± 22.4)% before and (17.8 ± 16.0)% after the procedures; obstruction in the left main bronchus was (71.1 ± 23.9)% before and (27.0 ± 24.0)% after the procedures; and the right main bronchus was (73.0 ± 26.2)% before and (34.9 ± 29.8)% after the procedures, (t=21.85, 12.27, 11.17 separately, P<0.01). Spirometry revealed that FEV1 improved significantly from (1.6 ± 0.8) L before to (2.0 ± 0.8) L after the procedures. Besides, many sophisticated procedures, such as stent implantation, corrupted metal stent removing and lithotripsy were performed under rigid bronchoscopy. There were no fatal complications. CONCLUSIONS: Rigid bronchoscopy provides immediate relief of central airway obstruction and maintains proper ventilation during sophisticated intraluminal operations. It provides better visualization for advanced procedures and is an optimal selection for securing the airway in severe central airway obstruction even with respiratory failure.

[Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in pulmonary sarcoidosis].

OBJECTIVE: The aim of this study was to observe the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in sarcoidosis. METHODS: We retrospectively analyzed the diagnostic efficiency of standard bronchoscopy and EBUS-TBNA in all patients diagnosed as sarcoidosis in Peking University First Hospitals between August 2010 and October 2011. The relationship between biopsy puncture numbers and sensitivity was calculated. RESULTS: There were 17 sarcoidosis patients among a total of 107 patients who had received EBUS-TBNA. Forteen patients had a positive TBNA result and the sensitive of EBUS-TBNA was 82%. The sensitivity of standard brochoscopy was 53% and when combined with EBUS-TBNA, the sensitivity increased to 88%. The sensitivity of EBUS-TBNA was associated with the size of lymph nodes. Lymph nodes with a diameter ≥ 2 cm showed a higher positive rate. Four punctures for 1 lymph node showed a concordance rate of 100% with the final results. CONCLUSIONS: EBUS-TBNA was a safe and effective method in diagnosing pulmonary sarcoidosis. For patients with suspected sarcoidosis EBUS-TBNA should be performed in the largest lymph nodes with at least 4 punctures.

In vitro batch fermentation demonstrates variations in the regulation of gut microbiota and metabolic functions by ß-glucans of differing structures.

The gut microbiota is widely acknowledged as a crucial factor in regulating host health. The structure of dietary fibers determines changes in the gut microbiota and metabolic differences resulting from their fermentation, which in turn affect gut microbe-related health effects. ß-Glucan (BG) is a widely accessible dietary fiber to humans, and its structural characteristics vary depending on the source. However, the interactions between different structural BGs and gut microbiota remain unclear. This study used an in vitro fermentation model to investigate the effects of BG on gut microbiota, and microbiomics and metabolomics techniques to explore the relationship between the structure of BG, bacterial communities, and metabolic profiles. The four sources of BG (barley, yeast, algae, and microbial fermentation) contained different types and proportions of glycosidic bonds, which differentially altered the bacterial community. The BG from algal sources, which contained only ß(1 â†’ 4) glycosidic bonds, was the least metabolized by the gut microbiota and caused limited metabolic changes. The other three BGs contain more diverse glycosidic bonds and can be degraded by bacteria from multiple genera, causing a wider range of metabolic changes. This work also suggested potential synergistic degradation relationships between gut bacteria based on BG. Overall, this study deepens the structural characterization-microbial-functional understanding of BGs and provides theoretical support for the development of gut microbiota-targeted foods.

In Vitro Inhibitory Effects of Polyphenols from Flos sophorae immaturus on α-Glucosidase: Action Mechanism, Isothermal Titration Calorimetry and Molecular Docking Analysis.

Flos sophorae immaturus (FSI) is considered to be a natural hypoglycemic product with the potential for a-glucosidase inhibitory activity. In this work, the polyphenols with α-glucosidase inhibition in FSI were identified, and then their potential mechanisms were investigated by omission assay, interaction, type of inhibition, fluorescence spectroscopy, circular dichroism, isothermal titration calorimetry and molecular docking analysis. The results showed that five polyphenols, namely rutin, quercetin, hyperoside, quercitrin and kaempferol, were identified as a-glucosidase inhibitors with IC50 values of 57, 0.21, 12.77, 25.37 and 0.55 mg/mL, respectively. Quercetin plays a considerable a-glucosidase inhibition role in FSI. Furthermore, the combination of quercetin with kaempferol generated a subadditive effect, and the combination of quercetin with rutin, hyperoside and quercitrin exhibited an interference effect. The results of inhibition kinetics, fluorescence spectroscopy, isothermal titration calorimetry and molecular docking analysis showed that the five polyphenols were mixed inhibitors and significantly burst the fluorescence intensity of α-glucosidase. Moreover, the isothermal titration calorimetry and molecular docking analysis showed that the binding to α-glucosidase was a spontaneous heat-trapping process, with hydrophobic interactions and hydrogen bonding being the key drivers. In general, rutin, quercetin, hyperoside, quercitrin and kaempferol in FSI are potential α-glucosidase inhibitors.

Influence of Ultrasound-Assisted Vacuum Drying on Physicochemical Characteristics, Antioxidant Activity, and α-Glucosidase Inhibition Activity of Flos Sophorae Immaturus.

Flos Sophorae Immaturus (FSI) contains a large number of bioactive substances with antioxidant and hypoglycaemic activity. However, a feasible drying process plays an important role in the retention of its biological activity. The present work investigated the effects of ultrasound-assisted vacuum drying (UAVD) on FSI samples in terms of drying time, colour, microstructure, and total flavonoid content (TFC). Meanwhile, the antioxidant activity and α-glucosidase inhibition activity were also evaluated. The results show that the drying time of UVAD samples was decreased by 40% compared to that of the single vacuum-dried (VD) samples (600 W for 10 min). The cellular porous structures of FSI tissue were formed by UAVD, which promoted the migration of water from the inside to the outside. Furthermore, samples treated by UAVD exhibited better antioxidant activities and α-glucosidase and α-amylase inhibition capacities, with DPPH (81.86%), ABTS (88.61%), FRAP (83.05%), α-glucosidase inhibition capacity (89%), α-amylase (85%), drying time (3 h), and total aberration (ΔE) (1.63) being the highest characteristic traits. In this condition, the highest levels of total flavonoid content (TFC), rutin, quercetin, kaempferol, isorhamnetin, and genistein were obtained with 266.94, 239.46, 35.56, 8.54, 10.37, and 5.64 mg/g DW, respectively. The results confirm that UAVD is a novel method that significantly reduced the VD time and promoted the release of the bioactive substances of FSI.

In vitro inhibitory effects of polyphenols from Tartary buckwheat on xanthine oxidase: Identification, inhibitory activity, and action mechanism.

The xanthine oxidase (XO) inhibitory activity is an important way to evaluate the anti-hyperuricemia effect of natural products. In the present work, the XO inhibitory effect of Tartary buckwheat was elucidated by polyphenols determination, omission experiment, interaction assay, inhibition types, fluorescence spectroscopy, and molecular docking. The results revealed that eight primary polyphenols were identified, including rutin (544 mg/100 g) and quercetin (261 mg/100 g). Quercetin (IC50 = 0.03 mg/mL) was a mixed-type inhibitor and exhibited the strongest inhibitory effect, followed by kaempferol (IC50 = 0.11 mg/mL). Moreover, a sub-additive effect was exhibited in the complex of quercetin-kaempferol, but the combination of quercetin and other polyphenols caused interference or antagonism effects. Furthermore, quercetin and kaempferol showed an obvious fluorescence quenching effect on XO, and the bindings were mainly driven by hydrophobic forces and hydrogen bonds. This study shows that Tartary buckwheat may be a potential functional food to inhibit XO activity.

Impact of Upper Airway Characteristics on Disease Severity and CPAP Therapy in Chinese Patients With OSA: An Observational Retrospective Study.

Objective: The characteristics of the upper airway (UA) are important for the evaluation and treatment of obstructive sleep apnea (OSA). This study aimed to investigate the association of UA characteristics with OSA severity, titration pressure, and initiation of and 3-month compliance with continuous positive airway pressure (CPAP). Methods: This retrospective study included consecutive patients examined using a semi-quantitative UA evaluation system (combination with physical examination and awake endoscopy) during 2008-2018 at the Department of Respiratory and Critical Care Medicine, Peking University First Hospital. First, the differences in UA characteristics were compared between patients with simple snorers and mild OSA and those with moderate-to-severe OSA. Then, the effect of UA characteristics on the initiation to CPAP therapy and 3-month adherence to CPAP was conducted. Results: Overall, 1,002 patients were included, including 276 simple snorers and patients in the mild OSA group [apnea-hypopnea index (AHI) <15] and 726 patients in the moderate-to-severe OSA group (AHI ≥15). Tongue base hypertrophy, tonsillar hypertrophy, mandibular recession, neck circumstance, and body mass index (BMI) were independent risk factors for moderate-to-severe OSA. Among those patients, 119 patients underwent CPAP titration in the sleep lab. The CPAP pressures in patients with thick and long uvulas, tonsillar hypertrophy, lateral pharyngeal wall stenosis, and tongue hypertrophy were higher than those of the control group (P < 0.05, respectively). The logistic regression analysis showed that nasal turbinate hypertrophy, mandibular retrusion, and positive Müller maneuver in the retropalate and retroglottal regions were independent predictors for the initiation of home CPAP treatment. Conclusion: Multisite narrowing and function collapse of the UA are important factors affecting OSA severity, CPAP titration pressure, and the initiation of home CPAP therapy. Clinical evaluation with awake endoscopy is a safe and effective way for the assessment of patients with OSA in internal medicine.

Photodynamic Therapy for Recurrent Early Central Lung Cancer of Great Longitudinal Extent Following Two Surgical Lung Resections: A Case Report.

Photodynamic therapy (PDT) is an endobronchial treatment requiring a photosensitizer activated by a specific wavelength light to kill tumor cells. PDT is effective in treating early central lung cancer (ECLC) ,especially for lesions <1.0 cm in length. We present a patient with history of two lung resections for squamous cell carcinoma, who had unresectable ECLC lesions (4.0 - 5.0 cm in length) treated by PDTs successfully without other modalities, such as radiotherapy or chemotherapy. After sequential PDTs, the patient achieved complete response for 2 months and partial response for 16 months, with greatly improved quality of life, despite mild skin photosensitization and acute exacerbation of chronic obstructive pulmonary disease. There was no evidence of metastasis during standard evaluation. As it was less-invasive and highly targeted, PDT might be a relatively safe and effective alternative therapy for ECLC lesions unsuitable for surgery, even lesions longer than 1.0 cm.

G Protein-Coupled Receptor 109A Maintains the Intestinal Integrity and Protects Against ETEC Mucosal Infection by Promoting IgA Secretion.

Several studies have reported an intricate link between the G protein-coupled receptor 109A (GPR109A) and intestinal health. Upon activation, induced by butyric acid and ß-hydroxybutyric acid, GPR109A regulates the expression of tight junction proteins, exerts anti-inflammatory effects, and maintains the integrity of the intestinal barrier. However, its function and the mechanism of action in combating the infection caused by exogenous pathogenic microorganisms remain unclear. This study established an animal model of infection by oral enterotoxigenic Escherichia coli (ETEC) gavage to examine the underlying mechanism(s) and protective effects of GPR109A on the intestinal tract. Experimental GPR109A-/-and GPR109A+/+ mice were orally administered with 1 × 109 colony-forming units (CFUs) of ETEC, and changes in body weight were then observed. The colonization and translocation of ETEC in the intestine were detected by the plate counting method. The expression of tight junction proteins and the levels of inflammatory factors and secretory IgA (SIgA) in the intestine were detected by quantitative real-time polymerase chain reaction (q-PCR), western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The results demonstrated that GPR109A-/-mice were more susceptible to ETEC infection, showing more severe inflammatory reactions and intestinal damage. Moreover, the secretion of IgA in the intestinal tract of GPR109A+/+ mice was significantly increased after ETEC infection, whereas the IgA levels in GPR109A-/-mice did not change significantly. We added 5 g/L sodium butyrate to the drinking water of all mice. The GPR109A+/+ mice were protected against ETEC infection and no effect was observed in GPR109A-/-mice. Similarly, sodium butyrate increased the SIgA content in the gut of the GPR109A+/+ mice and no effect was observed in GPR109A-/-mice. In conclusion, activated GPR109A is effective against the colonization and translocation of ETEC in the gut and maintains the integrity of the intestinal barrier, possibly by promoting the secretion of intestinal IgA.