Serine synthesis sustains macrophage IL-1ß production via NAD+-dependent protein acetylation.

Serine metabolism is involved in the fate decisions of immune cells; however, whether and how de novo serine synthesis shapes innate immune cell function remain unknown. Here, we first demonstrated that inflammatory macrophages have high expression of phosphoglycerate dehydrogenase (PHGDH, the rate-limiting enzyme of de novo serine synthesis) via nuclear factor κB signaling. Notably, the pharmacological inhibition or genetic modulation of PHGDH limits macrophage interleukin (IL)-1ß production through NAD+ accumulation and subsequent NAD+-dependent SIRT1 and SIRT3 expression and activity. Mechanistically, PHGDH not only sustains IL-1ß expression through H3K9/27 acetylation-mediated transcriptional activation of Toll-like receptor 4 but also supports IL-1ß maturation via NLRP3-K21/22/24/ASC-K21/22/24 acetylation-mediated activation of the NLRP3 inflammasome. Moreover, mice with myeloid-specific depletion of Phgdh show alleviated inflammatory responses in lipopolysaccharide-induced systemic inflammation. This study reveals a network by which a metabolic enzyme, involved in de novo serine synthesis, mediates post-translational modifications and epigenetic regulation to orchestrate IL-1ß production, providing a potential inflammatory disease target.

GABA signaling enforces intestinal germinal center B cell differentiation.

Recent compelling results indicate possible links between neurotransmitters, intestinal mucosal IgA+ B cell responses, and immunoglobulin A nephropathy (IgAN) pathogenesis. Here, we demonstrated that γ-amino butyric acid (GABA) transporter-2 (GAT-2) deficiency induces intestinal germinal center (GC) B cell differentiation and worsens the symptoms of IgAN in a mouse model. Mechanistically, GAT-2 deficiency enhances GC B cell differentiation through activation of GABA-mammalian target of rapamycin complex 1 (mTORC1) signaling. In addition, IgAN patients have lower GAT-2 expression but higher activation of mTORC1 in blood B cells, and both are correlated with kidney function in IgAN patients. Collectively, this study describes GABA signaling-mediated intestinal mucosal immunity as a previously unstudied pathogenesis mechanism of IgAN and challenges the current paradigms of IgAN.

Melatonin in food allergy: Mechanism and potential therapy.

Food allergy affects more than 500 million people in the world, and its prevalence is increasing at an alarming rate causing serious public health concerns; however, prevention and treatment methods are still under investigation and are relatively scarce so far. Insights on pathophysiology reveal a complex interplay of the immune cells (e.g., DCs, T cells, and B cells) resulting in allergy or tolerance. Studies have shown that melatonin metabolisms are altered in patients with allergic diseases, suggesting that melatonin might impact allergic diseases. Notably, melatonin can orchestrate the differentiation and function of immune cells. Additionally, the disease severities of many allergic diseases and the function of the immune system exhibit circadian rhythmicity. Therefore, melatonin, a rhythm regulator, may also act indirectly on the immune system through the circadian clock to regulate food allergies. Herein, we reviewed the impacts of melatonin on food allergy and its underlying regulatory mechanisms, providing a theoretical reference for melatonin as effective means of prevention and treatment for food allergy in the future.

Parathyroidectomy Is Associated With Reversed Nondipping Heart Rate That Impacts Mortality in Chronic Kidney Disease Patients.

OBJECTIVE: Nondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown. METHODS: This case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months). RESULTS: The HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL). CONCLUSION: CKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.

A risk prediction model for contrast-induced nephropathy associated with gadolinium-based contrast agents.

OBJECTIVE: This is the first study to explore the risk factors for nephropathy caused by gadolinium-based contrast agents and establish a prediction model to identify high-risk patients. METHODS: A total of 1404 patients who received gadolinium-based contrast agents in our hospital were included. The participants were randomly assigned in a 7:3 ratio to the modeling and validation groups. The modeling group was divided into a contrast-induced nephropathy group and a non-contrast-induced nephropathy group. The clinical characteristics before the use of contrast agents were compared between the two groups. The risk factors for contrast-induced nephropathy were analyzed by logistic regression. A nomogram that could predict the incidence of contrast-induced nephropathy was plotted. The validation group was used to verify the predictive model. RESULTS: The incidence of contrast-induced nephropathy caused by gadolinium-based contrast agents was 3.92% (55/1404). The logistic stepwise regression analysis showed that sex, systolic pressure (SBP), absolute neutrophil count, albumin, fasting blood glucose level, and furosemide use were significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. The above predictors were then included in the nomogram construction. The area under the receiver operating characteristic (ROC) curve was 0.82 (p < 0.001). The specificity and sensitivity corresponding to the optimal cutoff point (0.039) based on the area under the ROC curve were 71.9% and 80.5%, respectively. CONCLUSION: Sex, SBP, absolute neutrophil count, albumin, fasting blood glucose levels, and furosemide use are significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. Therefore, the incidence of contrast-induced nephropathy may be estimated by the prediction model established in this study before the use of contrast agents.

Protein restriction and cancer.

Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers.

Melatonin and other indoles show antiviral activities against swine coronaviruses in vitro at pharmacological concentrations.

The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights major gaps in our knowledge on the prevention control and cross-species transmission mechanisms of animal coronaviruses. Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine delta coronavirus (PDCoV) are three common swine coronaviruses and have similar clinical features. In the absence of effective treatments, they have led to significant economic losses in the swine industry worldwide. We reported that indoles exerted potent activity against swine coronaviruses, the molecules used included melatonin, indole, tryptamine, and L-tryptophan. Herein, we did further systematic studies with melatonin, a ubiquitous and versatile molecule, and found it inhibited TGEV, PEDV, and PDCoV infection in PK-15, Vero, or LLC-PK1 cells by reducing viral entry and replication, respectively. Collectively, we provide the molecular basis for the development of new treatments based on the ability of indoles to control TGEV, PEDV, and PDCoV infection and spread.

Diagnostic Values of Intraoperative (1-84) Parathyroid Hormone Levels are Superior to Intact Parathyroid Hormone for Successful Parathyroidectomy in Patients With Chronic Kidney Disease.

OBJECTIVE: Persistent secondary hyperparathyroidism (SHPT) may occur because of residual cervicothoracic parathyroids in parathyroidectomy (PTX) patients with chronic kidney disease. We prospectively compared the predictive values of intraoperative plasma (1-84) parathyroid hormone (PTH) and intact PTH (iPTH) levels to improve the safety and efficacy of PTX. METHODS: We included 100 healthy controls, 162 stage 5 chronic kidney disease patients without SHPT, and 214 patients who underwent PTX because of SHPT. Plasma iPTH and (1-84) PTH levels were measured before incision (io-iPTH0 and io-[1-84]PTH0, respectively) and 10 minutes (io-iPTH10 and io-[1-84]PTH10, respectively) and 20 minutes (io-iPTH20 and io-[1-84]PTH20, respectively) after removing all parathyroids. The percentage reduction of iPTH and (1-84) PTH at 10 minutes (io-iPTH10% and io-[1-84]PTH10%, respectively) and 20 minutes (io-iPTH20%, and io-[1-84]PTH20%, respectively) was calculated. iPTH and (1-84) PTH were measured using second- and third-generation PTH assays, respectively. RESULTS: Compared with the controls and non-PTX patients, the PTX group had more obvious mineral metabolism disorders. There were 187 successful PTXs, 19 patients with persistent SHPT, and 8 patients lost to follow-up. The receiver operating characteristic curves revealed that io-(1-84)PTH10% >86.6% and io-(1-84)PTH20% >87.5% suggested successful PTX. The sensitivity of io-iPTH20% and io-(1-84)PTH20% were higher than those at the timepoint of 10 minutes. Moreover, the specificity and sensitivity of the (1-84) PTH reduction percentage were superior to that of iPTH. CONCLUSION: Intraoperative reduction percentages of plasma (1-84) PTH levels are superior to iPTH for accurately predicting successful PTX, especially at 20 minutes after all cervicothoracic parathyroids had been resected.

Effects of parathyroidectomy on plasma PTH fragments and heart rate variability in stage 5 chronic kidney disease patients.

INTRODUCTION: Circulating intact parathyroid hormone (iPTH) levels include full-length (1-84) PTH and long C-PTH fragments, but primarily (7-84) PTH, which have been reported to have antagonistic effects on the bones and kidneys. However, their effects on the cardiovascular system remain unclear. In this study, the relationships between the plasma PTH fragments levels and heart rate variability (HRV) in stage 5 chronic kidney disease (CKD5) patients are explored. Furthermore, the effects of parathyroidectomy (PTX) on the above indices are investigated. METHODS: In this cross-sectional study, 164 healthy controls and 354 CKD5 patients, including 208 secondary hyperparathyroidism (SHPT) subgroup with PTX, were enrolled. Circulating (7-84) PTH levels were calculated by subtracting plasma (1-84) PTH levels from iPTH levels. The HRV parameters were measured using a 24-hour Holter. RESULTS: The baseline levels of plasma iPTH, (1-84) PTH, and (7-84) PTH in the CKD5 patients were 930.40 (160.65, 1792.50) pg/mL, 448.60 (99.62, 850.45) pg/mL, and 468.20 (54.22, 922.55) pg/mL, respectively. In the CKD5 patients, plasma (1-84) PTH levels were independently correlated with the standard deviation of the normal-to-normal R-R intervals (SDNN) and the standard deviation of the five-minute average of the normal R-R intervals (SDANN). With a median follow up time of 6.50 months after PTX in the SHPT patients (n = 30), improved SDNN and SDANN markers were related with decreased (1-84) PTH levels. Furthermore, an improved SDNN was related with decreased (7-84) PTH levels. CONCLUSIONS: The CKD5 patients' baseline (1-84) PTH levels were correlated with the SDNN and SDANN. After PTX, an improved SDNN was related with decreased (1-84) PTH and (7-84) PTH levels, while improved SDANN was related with decreased (1-84) PTH levels. No antagonistic effects of (1-84) PTH and (7-84) PTH on HRV were found in the CKD5 patients.

The relationship between urinary kidney injury molecule-1 and blood bone metabolism markers in patients with chronic kidney disease
.

OBJECTIVE: The aim of this study was to evaluate the changes of urinary kidney injury molecule-1(uKIM-1) in chronic kidney disease (CKD) at different stages, and to determine the relationships between uKIM-1 and circulating bone metabolism markers. MATERIALS AND METHODS: This cross-sectional study included CKD patients (n = 121) and controls (n = 65). CKD stages were assigned to each individual according to their estimated glomerular filtration rate (eGFR), which was calculated with the modification of diet in renal disease (MDRD) equation. We evaluated the relationships of bone metabolism markers (including calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D (25(OH)D), alkaline phosphatase (ALP), fibroblast growth factor 23 (FGF23), and α-Klotho), uKIM-1, and eGFR. We also compared the levels of bone metabolism markers and uKIM-1 at different CKD stages. The uKIM-1 level was standardized with urine creatinine (uCr). RESULTS: Compared with healthy controls, CKD patients had higher levels of uKIM-1/uCr, serum creatinine, urea, phosphorus, iPTH, and plasma FGF23, whereas they had lower levels of serum calcium, α-Klotho, and plasma 25(OH)D. In CKD patients, eGFR was positively correlated with levels of serum calcium, α-Klotho, and plasma 25(OH)D, whereas it was negatively correlated with serum phosphorus, iPTH, plasma FGF23, and uKIM-1/uCr. Serum calcium and α-Klotho were significantly decreased in patients with stage 5 CKD compared to those with stage 1 CKD. Serum phosphorus, iPTH, and plasma FGF23 were significantly elevated in patients with stage 4 CKD when compared to those with stage 1 CKD. UKIM-1/uCr was significantly elevated in patients with stage 5 CKD when compared to those with stage 1 CKD. In CKD patients, uKIM-1/uCr levels were positively correlated with levels of serum phosphorus and plasma FGF23, whereas they were negatively correlated with serum calcium and plasma 25(OH)D. CONCLUSION: UKIM-1/uCr levels are increased with the deterioration of CKD stage and are correlated with the development of CKD-mineral and bone disorder (CKD-MBD).

The role of bacterial cell envelope structures in acid stress resistance in E. coli.

Acid resistance (AR) is an indispensable mechanism for the survival of neutralophilic bacteria, such as Escherichia coli (E. coli) strains that survive in the gastrointestinal tract. E. coli acid tolerance has been extensively studied during past decades, with most studies focused on gene regulation and mechanisms. However, the role of cell membrane structure in the context of acid stress resistance has not been discussed in depth. Here, we provide a comprehensive review of the roles and mechanisms of the E. coli cell envelope from different membrane components, such as membrane proteins, fatty acids, chaperones, and proton-consuming systems, and particularly focus on the innovative effects revealed by recent studies. We hope that the information guides us to understand the bacterial survival strategies under acid stress and to further explore the AR regulatory mechanisms to prevent or treat E. coli and other related Gram-negative bacteria infection, or to enhance the AR of engineering E. coli.

Serum Alkaline Phosphatase Level Predicts Cardiac Valve Calcification in Maintenance Hemodialysis Patients.

PURPOSE: Cardiac valve calcification (CVC) is frequently occurred in maintenance hemodialysis (MHD) patients and is associated with cardiovascular and all-cause mortality. This study aimed to evaluate the relationships between risk factors and extent of CVC and further provide the treatment target in MHD patients. METHODS: One hundred and forty-five patients who received MHD ≥3 months were enrolled. CVC was assessed by an echocardiographic, semi-quantitative manner called global cardiac calcium scoring system (GCCS), and demographic, clinical, and laboratory parameters including mineral metabolism markers were collected. RESULTS: The average age of the patients was 50 ± 12 years, and 54.5% were men. The mean GCCS was 1.8 ± 2.4; 57.2% of patients had GCCS ≥1. Age, dialysis vintage, serum alkaline phosphatase (ALP), and intact parathyroid hormone levels were positively correlated with CVC, whereas serum albumin levels were negatively related to CVC, based on univariate analysis. With multivariate linear regression analysis, serum ALP was the only bone-derived biomarker that showed significant correlation with CVC. Serum ALP ≥232 U/L was a robust predictor of CVC and was associated with the likelihood of GCCS ≥1 (OR 3.92, 95% CI 1.37-11.2, p = 0.011). The decision tree model was used to identify ALP ≥232 U/L and age ≥60 years as important determinative variables in the prediction of CVC in MHD patients. CONCLUSION: Serum ALP level is significantly associated with CVC in MHD patients. ALP is suggested to be a promising interventional target for cardiovascular calcification in MHD patients.

Impacts of Amino Acids on the Intestinal Defensive System.

The intestine interacts with a diverse community of antigens and bacteria. To keep its homeostasis, the gut has evolved with a complex defense system, including intestinal microbiota, epithelial layer and lamina propria. Various factors (e.g., nutrients) affect the intestinal defensive system and progression of intestinal diseases. This review highlights the current understanding about the role of amino acids (AAs) in protecting the intestine from harm. Amino acids (e.g., arginine, glutamine and tryptophan) are essential for the function of intestinal microbiota, epithelial cells, tight junction, goblet cells, Paneth cells and immune cells (e.g., macrophages, B cells and T cells). Through the modulation of the intestinal defensive system, AAs maintain the integrity and function of the intestinal mucosa and inhibit the progression of various intestinal diseases (e.g., intestinal infection and intestinal colitis). Thus, adequate intake of functional AAs is crucial for intestinal and whole-body health in humans and other animals.

Comparison of microwave ablation treatments in patients with renal secondary and primary hyperparathyroidism.

Purpose: Microwave ablation (MWA) is feasible for severe renal secondary hyperparathyroidism (SHPT) and primary hyperparathyroidism (PHPT) patients ineligible for parathyroidectomy (PTX). Here we compared the clinical manifestations and characteristics of parathyroid glands in these two groups, and summarized the techniques, safety and efficacy of MWA.Methods: Baseline clinical characteristics, ablation-related techniques, adverse events/complications, and efficacy were recorded.Results: In SHPT group, malnutrition, cardiovascular/pulmonary complications, and abnormal bone metabolism were severe. SHPT patients had more hyperplastic parathyroid glands. The volume of each gland was smaller, and the time of ablation for a single parathyroid was shorter in the SHPT group, although there were no significant differences compared with patients in the PHPT group. Three patients in both groups had recurrent laryngeal nerve injuries and all recovered, except for one SHPT patient. By the end of follow-up, serum iPTH levels had decreased from 2400.26 ± 844.26 pg/mL to 429.39 ± 407.93 pg/mL (p < .01) in SHPT and from 297.73 ± 295.32 pg/mL to 72.22 ± 36.51 pg/mL in PHPT group (p < .01). Hypocalcemia was more common (p < .001) and serum iPTH levels were prone to rebound in SHPT patients after MWA.Conclusion: MWA can be reserved for those who had high surgical risks because of less invasiveness. Injuries of recurrent laryngeal nerves should be noticed. The health status, perioperative, and intraoperative procedures were more complicated and all parathyroids found by ultrasound should be ablated completely in SHPT patients.

l-Serine Lowers the Inflammatory Responses during Pasteurella multocida Infection.

Pasteurella multocida causes a variety of infectious diseases in various species of mammals and birds, resulting in enormous economic loss to the modern livestock and poultry industry. However, the mechanism of host-pathogen interaction is unclear. Here, we found that l-serine levels were significantly decreased in murine lungs infected with P. multocida Exogenous l-serine supplementation significantly increased the survival rate of mice and decreased the colonization of P. multocida in the lungs of mice. Notably, l-serine decreased the macrophage- and neutrophil-mediated inflammatory responses in mice during P. multocida infection.

Melatonin in macrophage biology: Current understanding and future perspectives.

Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage-associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF-κB, STATs, and NLRP3/caspase-1. Notably, miRNAs (eg, miR-155/-34a/-23a), cellular metabolic pathways (eg, α-KG, HIF-1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage-associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage-associated diseases.

Enterotoxigenic Escherichia coli infection promotes apoptosis in piglets.

Enterotoxigenic Escherichia coli (ETEC), as a universal pathogen, often causes diarrhea in animals and humans. However, whether ETEC infection induces apoptosis in host remains controversial. Herein, we use ETEC-infected piglet to investigate apoptosis in the jejunum. Apoptosis and the activation of capase-3 are observed in piglet jejunum after ETEC infection. Additionally, ETEC infection induces the activation of caspase-8 pathway, but inhibits the activation of caspase-9 pathway in piglet jejunum. These findings demonstrate that ETEC infection may inhibit the intrinsic pathway and activate the extrinsic pathway of apoptosis in piglets.

Hyperhomocysteinemia and cardiovascular disease in animal model.

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease and is associated with primary causes of mortality and morbidity throughout the world. Several studies have been carried out to evaluate the effects of a diet inducing cystathionine-ß-synthase, methyltetrafolate, folic acid, and vitamin B supplemented with methionine on the homocysteine metabolism and in lowering the plasma total homocysteine levels. A large number of molecular and biomedical studies in numerous animals, such as mice, rabbits, and pigs, have sought to elevate the plasma total homocysteine levels and to identify a disease model for human hyperhomocysteinemia. However, a specific animal model is not suitable for hyperhomocysteinemia in terms of all aspects of cardiovascular disease. In this review article, the experimental progress of animal models with plasma total homocysteine levels is examined to identify a feasible animal model of hyperhomocysteinemia for different aspects.

Melatonin alleviates weanling stress in mice: Involvement of intestinal microbiota.

Melatonin influences intestinal microbiota and the pathogenesis of various diseases. This study was conducted to explore whether melatonin alleviates weanling stress through intestinal microbiota in a weanling mouse model. Melatonin supplementation in weanling mice (provided in the drinking water at a dosage of 0.2 mg/mL for 2 weeks) significantly improved body weight gain (1.4 ± 0.03 g/day in melatonin group vs 1.2 ± 0.06 g/day in control group) and intestinal morphology (ie, villus length, crypt depth, and villus to crypt ratio), but had little effect on the proliferation or apoptosis of intestinal cells, the numbers of Paneth cells and goblet cells, as well as the expression of makers related to enterocytes (sucrase) and endocrine cells (chromogranin A and peptide YY) in the ileum. Melatonin supplementation had little effect on serum levels of amino acids or stress-related parameters (eg, SOD, TNF-α, and angiotensin I). 16S rRNA sequencing suggested that melatonin supplementation increased the richness indices of intestinal microbiota (observed species, Chao 1, and ACE) and shaped the composition of intestinal microbiota (eg, increase in the abundance of Lactobacillus [19 ± 3% in melatonin group vs 6 ± 2% in control group]), which was demonstrated using an ex vivo proliferation assay and colonic loop proliferation assay. Melatonin supplementation also significantly influenced the metabolism of intestinal microbiota, such as amino acid metabolism and drug metabolism. More importantly, in antibiotic-treated weanling mice and germ-free weanling mice, melatonin failed to affect body weight gain or intestinal morphology. Melatonin significantly reduced (by about 60%) the bacterial load in enterotoxigenic Escherichia coli (ETEC)-infected weanling mice, but had little effect on ETEC load in antibiotic-pretreated animals. In conclusion, melatonin affects body weight gain, intestinal morphology, and intestinal ETEC infection through intestinal microbiota in weanling mice. The findings highlight the importance of intestinal microbiota in mediating the various physiological functions of melatonin in the host.

Melatonin reprogramming of gut microbiota improves lipid dysmetabolism in high-fat diet-fed mice.

Melatonin has been shown to improve lipid metabolism and gut microbiota communities in animals and humans; however, it remains to know whether melatonin prevents obesity through gut microbiota. Here, we found that high-fat diet promoted the lipid accumulation and intestinal microbiota dysbiosis in mice, while oral melatonin supplementation alleviated the lipid accumulation and reversed gut microbiota dysbiosis, including the diversity of intestinal microbiota, relative abundances of Bacteroides and Alistipes, and functional profiling of microbial communities, such as energy metabolism, lipid metabolism, and carbohydrate metabolism. Interestingly, melatonin failed to alleviate the high-fat-induced lipid accumulation in antibiotic-treated mice; however, microbiota transplantation from melatonin-treated mice alleviated high-fat diet-induced lipid metabolic disorders. Notably, short-chain fatty acids were decreased in high-fat diet-fed mice, while melatonin treatment improved the production of acetic acid. Correlation analysis found a marked correlation between production of acetic acid and relative abundances of Bacteroides and Alistipes. Importantly, sodium acetate treatment also alleviated high-fat diet-induced lipid metabolic disorders. Taken together, our results suggest that melatonin improves lipid metabolism in high-fat diet-fed mice, and the potential mechanisms may be associated with reprogramming gut microbiota, especially, Bacteroides and Alistipes-mediated acetic acid production. Future studies are needed for patients with metabolic syndrome to fully understand melatonin's effects on body weight and lipid profiles and the potential mechanism of gut microbiota.