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Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

Abstract Background The γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the “enteric nervous system–vagus nerve–brain” axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure. Methods Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice. Results The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system. Conclusions These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.

Abstract Background Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction. Methods A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed. Results Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P

Atopic dermatitis (AD) is a chronic, recurrent inflammatory disease characterized by itching. The gut microbiome can help maintain skin immune homeostasis by regulating innate and adaptive immunity. Here, we report a case of AD in a 15-year-old adolescent boy who benefited from washed microbiota transplantation (WMT). WMT was performed for three courses, with each course lasting for three consecutive days and an interval of one month between two courses. Clinical assessments were conducted at each WMT course, and skin, blood, and stool samples were collected for microbial analysis. After three months of WMT treatment, the boy’s itchiness was effectively controlled: his skin showed noticeable improvement, with reduced Staphylococcus aureus in the skin lesions. The scores of SCORAD (SCORing Atopic Dermatitis), EASI (Eczema Area and Severity Index), NRS (Numerical Rating Scale), and DLQI (Dermatology Life Quality Index) significantly decreased compared to the baseline. Serum levels of eosinophil ratio, tumor necrotic factor-α, and interleukin-6 also reduced to the normal levels. There was a significant decrease in S. aureus in the skin lesions. Additionally, the intestinal flora became more diverse, and the abundance of Bifidobacterium species, significantly increased after WMT. No adverse events were reported during the treatment and the 1-year follow-up period. This case report provides direct clinical evidence for WMT as a novel promising treatment strategy for AD, and preliminary experimental data suggests the existence of an intestinal-skin axis in terms of the gut microbiota and the skin immune homeostasis.

Background and objectiveEssential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice.MethodsSpecific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3 weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30 min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively.ResultsCompared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice.ConclusionMice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.

Background: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients. Methods: The changes in body mass index (BMI = weight (kg)/height (m)2), blood glucose, blood lipids and other indicators before and after WMT were compared. At the same time, 16S rRNA gene amplicon sequencing was performed on fecal samples of OW patients before and after transplantation. Finally, serum samples were tested for sphingolipids targeted by lipid metabolomics. Results: A total of 166 patients were included, including 52 in the OW group and 114 in the normal weight (NOW) group. For OW patients, WMT significantly improved the comprehensive efficacy of OW. In the short term (about 1 month) and medium term (about 2 months), a significant reduction in BMI was seen. At the same time, in the short term (about 1 month), liver fat attenuation (LFA), triglyceride (TG) and fasting blood glucose (FBG) were significantly reduced. In the long term (about 5 months), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein (non-HDL-c), etc. were significantly reduced. WMT improved the gut microbiota of OW patients, and also had an improvement effect on OW patients by regulating sphingolipid metabolism. Conclusion: WMT had a significant improvement effect on OW patients. WMT could restore gut microbiota homeostasis and improve OW patients by regulating sphingolipid metabolism.

ObjectiveWhile fecal microbiota transplantation is demonstrated to improve symptoms of autism spectrum disorder (ASD), it remains unclear whether additional treatment courses yield better results. This study sought to evaluate the efficacy of repeated washed microbiota transplantation (WMT) in children with ASD.MethodsRetrospective data from children who were serially treated with WMT, including ASD symptoms, sleep disorders, gastrointestinal (GI) symptoms, and white blood cell (WBC) and globulin levels were obtained. The effect of WMT on children with ASD and whether additional WMT courses led to a further improvement in symptoms were assessed.ResultsAberrant Behavior Checklist (ABC), Childhood Autism Rating Scale, and Sleep Disturbance Scale for Children (SDSC) scores, the proportion of children with constipation and abnormal fecal forms, and WBC and globulin levels were all significantly lower in ASD children after WMT. More WMT treatment courses led to significantly lower scores on the ABC and SDSC.ConclusionWMT significantly improved ASD and GI symptoms and sleep disorders in children with ASD, and reduced systemic inflammation. Additional WMT courses led to more obvious improvements in ASD symptoms within three treatment courses.

Background and AimsAlthough the manual crude fecal microbiota transplantation (FMT) reduces blood lipids in animal models of hyperlipidemia, its clinical effect on blood lipid metabolism in patients with hyperlipidemia and hypolipidemia remains unclear, especially in the Chinese population. It was reported that washed microbiota transplantation (WMT) was safer, more precise, and more quality-controllable than the crude FMT by manual. This study aimed to investigate the feasibility and effectiveness of WMT on lipid metabolism in the Chinese population.MethodsClinical data of patients with various indications who received WMT for 1–3 treatment procedures were collected. Changes in blood lipids before and after WMT, namely, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), liver fat attenuation, and liver stiffness measurement, were compared.ResultsA total of 177 patients (40 cases of hyperlipidemia, 87 cases with normal blood lipids, and 50 cases of hypolipidemia) were enrolled in the First Affiliated Hospital of Guangdong Pharmaceutical University. WMT has a significant therapeutic effect in reducing blood lipid levels (TC and TG) in the short- and medium term in patients with hyperlipidemia (p

Background. Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease that can cause various complications, including systemic inflammatory response syndrome (SIRS), pleural effusion, ascitic fluid, myocardial infarction, and acute kidney injury (AKI). However, there is still a lack of rapid and effective indicators to assess the disease. The aim of this study was to investigate the associations of high serum lactate dehydrogenase (LDH) levels with AP severity and systemic complications. Methods. AP patients treated from July 2014 to December 2020 were retrospectively enrolled. They were divided into elevated (n=93) and normal (n=143) LDH groups. Their demographic data, clinical data, hospital duration, and hospital expenses were analyzed. Linear and binary logistic regression analyses were used to determine whether elevated LDH is a risk factor for AP severity and complications after adjusting for confounders. Results. There were significant differences in AP severity scores (Ranson, MODS, BISAP, APACHE II, and CTSI), hospital duration, hospital expenses, and the incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI) between the elevated and normal LDH groups. After adjusting for confounders, elevated LDH was associated with AP severity scores and hospital duration and expenses (based on linear regression analyses) and was a risk factor for the occurrence of AP complications and interventions, that is, diuretic and vasoactive agent use (based on binary logistic regression analyses). Conclusions. Elevated LDH is associated with high AP severity scores and high incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI).

BackgroundAlthough transplantation of the fecal microbiota from normotensive donors has been shown to have an antihypertensive effect in hypertensive animal models, its effect on blood pressure in patients with hypertension is unclear. This study aimed to assess the effect of washed microbiota transplantation (WMT) from normotensive donors on blood pressure regulation in hypertensive patients.MethodsThe clinical data of consecutive patients treated with washed microbiota transplantation (WMT) were collected retrospectively. The blood pressures of hypertensive patients before and after WMT were compared. The factors influencing the antihypertensive effect of WMT in hypertensive patients and fecal microbial composition of donors and hypertensive patients were also analyzed.ResultsWMT exhibited an antihypertensive effect on blood pressure: the blood pressure at hospital discharge was significantly lower than that at hospital admission (change in systolic blood pressure: −5.09 ± 15.51, P = 0.009; change in diastolic blood pressure: −7.74 ± 10.42, P < 0.001). Hypertensive patients who underwent WMT via the lower gastrointestinal tract (β = −8.308, standard error = 3.856, P = 0.036) and those not taking antihypertensive drugs (β = −8.969, standard error = 4.256, P = 0.040) had a greater decrease in systolic blood pressure, and hypertensive patients not taking antihypertensive drugs also had a greater decrease in diastolic blood pressure (β = −8.637, standard error = 2.861, P = 0.004). After WMT, the Shannon Diversity Index was higher in six of eight hypertensive patients and the microbial composition of post-WMT samples tended to be closer to that of donor samples.ConclusionWMT had a blood pressure-lowering effect in hypertensive patients, especially in those who underwent WMT via the lower gastrointestinal tract and in those not taking antihypertensive drugs. Therefore, modulation of the gut microbiota by WMT may offer a novel approach for hypertension treatment.

Background: Previous studies have indicated an association between hypertension and intestinal barrier dysfunction in mice models. The present study aims to investigate the association between hypertension and intestinal barrier impairment in humans and identify the novel potential risk factors for hypertension.Methods: Medical data from consecutive inpatients were retrospectively pooled from patient records. We compared intestinal barrier serum markers [diamine oxidase (DAO), lipopolysaccharide (LPS), and D-lactate] between those patients with and without hypertension. Moreover, the associations between intestinal barrier markers and cardiovascular risk, hypertension history, blood pressure control, hypertensive complications, and antihypertensive medication history were also analyzed.Results: Overall, 106 hypertensive and 251 normotensive subjects were included. Patients with hypertension had a higher level of DAO (28.30 vs. 18.73%, P = 0.044) and LPS (22.64 vs. 11.16%, P = 0.005). In hypertensive patients, multivariate logistic regression analyses showed that long hypertension history (≥20 years), poor control of diastolic blood pressure, cardiac and renal complications, and use of multiple antihypertensive medications were risk factors for elevated DAO, while the use of multiple antihypertensive medications was a risk factor for elevated D-lactate (P < 0.05).Conclusions: Hypertension is associated with impairment of intestinal barrier, especially in patients with long duration, poor blood pressure control, cardiac and renal complications, and use of multiple antihypertensive medications. The current study indicates that intestinal barrier dysfunction might be a potential predictor of hypertension.

BACKGROUND:The disease burden associated with influenza in developing tropical and subtropical countries is poorly understood owing to the lack of a comprehensive disease surveillance system and information-exchange mechanisms. The impact of influenza on outpatient visits, hospital admissions, and deaths has not been fully demonstrated to date in south China. METHODS:A time series Poisson generalized additive model was used to quantitatively assess influenza-like illness (ILI) and influenza disease burden by using influenza surveillance data in Zhuhai City from 2007 to 2009, combined with the outpatient, inpatient, and respiratory disease mortality data of the same period. RESULTS:The influenza activity in Zhuhai City demonstrated a typical subtropical seasonal pattern; however, each influenza virus subtype showed a specific transmission variation. The weekly ILI case number and virus isolation rate had a very close positive correlation (r = 0.774, P < 0.0001). The impact of ILI and influenza on weekly outpatient visits was statistically significant (P < 0.05). We determined that 10.7% of outpatient visits were associated with ILI and 1.88% were associated with influenza. ILI also had a significant influence on the hospitalization rates (P < 0.05), but mainly in populations 0.05). The impact of ILI on chronic obstructive pulmonary disease (COPD) was most significant (P < 0.05), with 33.1% of COPD-related deaths being attributable to ILI. The impact of influenza on the mortality rate requires further evaluation. CONCLUSIONS:ILI is a feasible indicator of influenza activity. Both ILI and influenza have a large impact on outpatient visits. Although ILI affects the number of hospital admissions and deaths, we found no consistent influence of influenza, which requires further assessment.

Clinical and experimental research has revealed that diabetes mellitus (DM) is characterized by intestinal hypomotility, gut microbial dysbiosis, increased gut permeability, microcirculation disorders, circulatory changes, and dysfunction of intestinal stem cells, which may be linked to inflammation of intestinal mucosa. However, the relationship between type 2 DM (T2DM) and macroscopic small intestinal mucosal injuries is still unclear. Therefore, we retrospectively studied capsule endoscopy data to determine the relationship between T2DM and small intestinal mucosal injuries.We compared the records of 38 T2DM patients with those of 152 non-DM patients for small intestinal mucosal injuries. Different types of mucosal injuries and Lewis scores were compared between T2DM and non-DM patients. The relationships between patients with or without different types of diabetic complications and the Lewis score was assessed. Moreover, the relationships between insulin resistance and Lewis score, between HbA1c and Lewis score, were also both assessed.The prevalence of a villous edema in subjects with T2DM was significantly higher than in those without DM (P < 0.001), but incidence of ulcers was not different (P = 1.000). With T2DM, the Lewis score was also significantly higher (P = 0.002). In addition, subjects with diabetic nephropathy showed significantly higher Lewis scores than patients without diabetic nephropathy (P = 0.033). In Pearson's correlation tests, the homeostasis model assessment of insulin resistance (HOMA-IR) value was correlated positively with the Lewis score (γ = 0.175, P = 0.015), but no statistical correlation was found between HbA1c level and Lewis score (γ = 0.039, P = 0.697).Subjects with T2DM, especially those with diabetic nephropathy, have higher Lewis scores and more serious small intestinal mucosal lesions.

OBJECTIVES: Frequent outbreaks of dengue are considered to be associated with an increased risk for endemicity of the disease. The occurrence of a large number of indigenous dengue cases in consecutive years indicates the possibility of a changing dengue epidemic pattern in Guangdong, China. METHODS: To have a clear understanding of the current dengue epidemic, a retrospective study of epidemiological profile, serological response, and virological features of dengue infections from 2005-2011 was conducted. Case data were collected from the National Notifiable Infectious Diseases Reporting Network. Serum samples were collected and prepared for serological verification and etiological confirmation. Incidence, temporal and spatial distribution, and the clinical manifestation of dengue infections were analyzed. Pearson's Chi-Square test was used to compare incidences between different age groups. A seroprevalence survey was implemented in local healthy inhabitants to obtain the overall positive rate for the specific immunoglobulin (Ig) G antibody against dengue virus (DENV). RESULTS: The overall annual incidence rate was 1.87/100000. A significant difference was found in age-specific incidence (Pearson's Chi-Square value 498.008, P