Short chain fatty acid: a messenger of gut-organ axis for disease regulation / 药学学报

Gut microbiota is a complex and dynamic system, and is essential for the health of the body. As the "second genome" of the body, it can establish communication with the important organs by regulating intestinal nerves, gastrointestinal hormones, intestinal barrier, immunity and metabolism, thus affecting host′s physiological functions. Short chain fatty acid (SCFA), known as one important metabolite of intestinal microbiota, is regarded as a significant messenger of the gut-organ communication, due to its extensive regulation in the body′s immunity, metabolism, endocrine and signal transduction. In this review, we summarize the interaction between gut-liver/brain/kidney/lung axis and diseases, and focus on the role and mechanism of SCFA in the gut-organ communication, hoping to provide new ideas for the treatment of the related diseases.

Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice / 中西医结合学报

OBJECTIVE@#Abnormalities in the gut microbiota and intestinal short-chain fatty acid (SCFA) levels are implicated in the pathogenesis of functional constipation (FC). Electro-acupuncture (EA) has been shown to improve constipation-related symptoms and rebalance the gut microbiota. However, it is currently unknown whether the gut microbiota is a key mechanistic target for EA or how EA promotes gut motility by regulating the gut microbiota and SCFAs. Therefore, we assessed the effects of EA in FC mice and pseudo-germfree (PGF) mice to address these questions.@*METHODS@#Forty female Kunming mice were randomly separated into a normal control group (n = 8), an FC group (n = 8), an FC + EA group (n = 8), a PGF group (n = 8) and a PGF + EA group (n = 8). The FC group and FC + EA group were treated with diphenoxylate to establish the FC model; the PGF group and PGF + EA group were given an antibiotic cocktail to initiate the PGF model. After maintaining the model for 14 d, mice in the FC + EA and PGF + EA groups received EA stimulation at the ST25 and ST37 acupoints, once a day, 5 times per week, for 2 weeks. Fecal parameters and intestinal transit rate were calculated to assess the efficacy of EA on constipation and gastrointestinal motility. Colonic contents were used to quantify gut microbial diversity using 16S rRNA sequencing, and measure SCFA concentrations using gas chromatography-mass spectrometry.@*RESULTS@#EA significantly shortened the first black stool defecation time (P < 0.05) and increased the intestinal transit rate (P < 0.01), and fecal pellet number (P < 0.05), wet weight (P < 0.05) and water content (P < 0.01) over 8 h, compared with the FC group, showing that EA promoted gut motility and alleviated constipation. However, EA treatment did not reverse slow-transit colonic motility in PGF mice (P > 0.05), demonstrating that the gut microbiota may play a mechanistic role in the EA treatment of constipation. In addition, EA treatment restored the Firmicutes to Bacteroidetes ratio and significantly increased butyric acid generation in FC mice (P < 0.05), most likely due to the upregulation of Staphylococcaceae microorganisms (P < 0.01).@*CONCLUSION@#EA-mediated resolution of constipation occurs through rebalancing the gut microbiota and promoting butyric acid generation. Please cite this article as: Xu MM, Guo Y, Chen Y, Zhang W, Wang L, Li Y. Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice. J Integr Med. 2023; Epub ahead of print.

Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. Radix Astragali, used as both medicine and food, exerts the effects of tonifying spleen and qi. Astragalus polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of Radix Astragali, which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1β (IL-1β), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-‍κB (TLR4/NF-‍κB) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella, and increasing that of Parasutterella, Parabacteroides, Clostridium XIVb, Oscillibacter, Butyricicoccus, and Dorea. APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.

Research progress on the role of short-chain fatty acids in the treatment of ulcerative colitis / 中华临床营养杂志

Short-chain fatty acids (SCFAs), as the main energy source for colonic epithelial cells, are becoming one of the important nutritional agents in the treatment of E1 (proctitis) and E2 (left-sided) subtypes of ulcerative colitis. To date, the therapeutic effects of topical SCFAs as primary or adjuvant induction therapy have been studied. However, the specific mechanism of action for SCFAs in the pathogenesis and progression of ulcerative colitis needs further investigation. High-quality prospective studies are required to verify current opinions on the selection of SCFA mixtures and the choice of topical or systemic routes of administration. In addition, SCFA is considered as a promising agent to prevent the occurrence and progression of ulcerative colitis-related colorectal cancer. Therefore, the optimal timing to integrate SCFAs into the treatment of ulcerative colitis represents another future research direction.

Dengzhan Shengmai inhibits nonalcoholic fatty liver disease via regulating intestinal microenvironment / 药学学报

The aim of this study was to investigate the efficacy and mechanism of Dengzhan Shengmai (DZSM) against nonalcoholic fatty liver diseases (NAFLD). The animal experiment program was reviewed and approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The NAFLD model of Syrian golden hamsters was established by high fat diets. After 6 weeks of DZSM treatment, the serum lipid, hepatic lipid accumulation, liver function and inflammatory response were determined. The regulations of gut microbiota and short-chain fatty acids were detected by 16S rRNA gene sequencing and gas chromatography-mass spectrometry method, respectively. The gut barrier function was evaluated by enzyme linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot and histopathological methods and further verified in HepG2 cells. The results showed that the efficacy of DZSM against NAFLD was remarkably reduced after removal of the gut microbiota. The study of mechanism showed that DZSM significantly regulated the composition of gut microbiota, promoted the production and absorption of intestinal short-chain fatty acids, then leading to the reduction of hepatic lipid accumulation. Moreover, after DZSM treatment, the decreased lipopolysaccharide (LPS) level by improving the intestinal barrier function significantly inhibited the hepatic inflammation through down-regulating Toll like receptor 4 (TLR4)-nuclear factor kappa B (NFKB) signaling pathway. These results indicate that DZSM inhibits NAFLD via regulating intestinal microenvironment.

Diagnosis and treatment strategy of intestinal flora imbalance after liver transplantation / 器官移植

Multiple short-term and long-term complications might occur after liver transplantation. In the early stage after liver transplantation, the incidence of multidrug-resistant bacteria is likely to cause different types of infection, one of which is intestinal flora imbalance. In the recent decade, a series of studies have demonstrated that intestinal flora plays an important role in maintaining intestinal homeostasis. Intestinal flora may interact with other organs via multiple patterns. Among which, gut-liver axis is one of the most critical channels for regulating microenvironment of the host. Changes in the quantity and composition of intestinal flora could lead to intestinal flora imbalance. In both local and systemic systems, extensive interaction exists between intestinal flora and immune system. In this article, the risk factors of intestinal flora imbalance after liver transplantation, influence of intestinal flora imbalance on liver transplant recipients and relevant treatment strategies were reviewed.

Effects of compound fermented milk on improving constipation in mice and underlying mechanism / 中华微生物学和免疫学杂志

Objective:To investigate the effects of compound fermented milk on intestinal microbiota, short chain fatty acid (SCFA), intestinal motility and mucosal barrier in mice with constipation.Methods:Twenty-seven C57BL/6JNifdc mice were randomly divided into three groups: control group, model group and intervention group. The model group and the intervention group were given loperamide intragastrically for two weeks. Starting from the second week, the intervention group was treated with compound fermented milk for 7 d. The control group was given normal saline. Food intake, water intake, weight change, fecal moisture content, time of first-time black stool and small intestine propulsion rate were detected. Expression of serotonin C receptor (5-HTR2C), zona occludins-1 (ZO-1) and mucin-2 (MUC-2) at mRNA level in colon was analyzed. Western blot was used to measure the expression of Raf/ERK/MAPK-related proteins. SCFA level in intestinal tract was detected by gas chromatography. Intestinal microbiota diversity was analyzed by high-throughput sequencing.Results:Compared with the control group, the first black stool excretion time was significantly prolonged in the model group ( P<0.01). Moreover, fecal moisture content, small intestine propulsion rate and the expression of 5-HTR2C and ZO-1 at mRNA level in colon were significantly decreased ( P<0.01). Compared with the model group, the first black stool excretion time was significantly shortened ( P<0.05); fecal moisture content, small intestine propelling rate ( P<0.05), the expression of colon 5-HTR2C and ZO-1 at mRNA level ( P<0.05), phosphorylation of Raf/ERK/MAPK pathway in the colon, intestinal SCFA-producing bacteria and intestinal SCFA content were increased in the intervention group. Conclusions:Compound fermented milk had a therapeutic effect on constipation in a mouse model by increasing the abundance of SCFA-producing bacteria and SCFA content, enhancing the phosphorylation of the Raf/ERK/MAPK pathway to up-regulate the expression of 5-HTR2C at mRNA level in the colon, and increasing the expression of ZO-1 at mRNA level in the colon. Intestinal peristalsis and intestinal mucosal barrier function were enhanced, thus improving the symptom of constipation.

Influence of enteral feeding initiation time on intestinal flora and metabolites in very low birth weight infants: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the influence of enteral feeding initiation time on intestinal flora and metabolites in very low birth weight (VLBW) infants.@*METHODS@#A total of 29 VLBW infants who were admitted to the Department of Neonatology, Children's Hospital of Chongqing Medical University, from June to December, 2020, were enrolled as subjects. According to the enteral feeding initiation time after birth, the infants were divided into two groups: <24 hours (n=15) and 24-72 hours (n=14). Fecal samples were collected at weeks 2 and 4 of hospitalization, and 16S rDNA high-throughput sequencing and gas chromatography-mass spectrometry were used to analyze the microflora and short-chain fatty acids (SCFAs) respectively in fecal samples.@*RESULTS@#The analysis of microflora showed that there was no significant difference between the two groups in Chao index (reflecting the abundance of microflora) and Shannon index (reflecting the diversity of microflora) at weeks 2 and 4 after birth (P>0.05). The analysis of flora composition showed that there was no significant difference in the main microflora at the phylum and genus levels between the two groups at weeks 2 and 4 after birth (P>0.05). The comparison of SCFAs between the two groups showed that the <24 hours group had a significantly higher level of propionic acid than the 24-72 hours group at week 4 (P<0.05), while there was no significant difference in the total amount of SCFAs and the content of the other SCFAs between the two groups (P>0.05).@*CONCLUSIONS@#Early enteral feeding has no influence on the diversity and abundance of intestinal flora in VLBW infants, but enteral feeding within 24 hours can increase the level of propionic acid, a metabolite of intestinal flora.

Gynostemma pentaphyllum saponins alleviate non-alcoholic fatty liver disease in rats by regulating intestinal flora and short-chain fatty acid metabolism / 中国中药杂志

This study aimed to explore the effects of Gynostemma pentaphyllum saponins(GPs) on non-alcoholic fatty liver disease(NAFLD) induced by high-fat diet in rats and reveal the underlying mechanism. The NAFLD model rats were prepared with high-fat diet. Forty male Sprague Dawley(SD) rats were randomly assigned into the control group, model group, and low-, moderate-, and high-dose GPs(50, 100, and 150 mg·kg~(-1), respectively) groups. After intragastric administration for 8 continuous weeks, we determined the body weight, liver weight, the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-c), high-density lipoprotein cholesterol(HDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum, and the levels of TC, TG, malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), and interleukin 6(IL-6) in the liver. Furthermore, we observed the pathological changes of liver tissue by oil red O staining and hematoxylin-eosin(HE) staining, sequenced the 16 S rRNA of the intestinal flora in rat feces, and determined the content of short-chain fatty acids in rat feces. The results showed that GPs inhibited the excessive weight gain of high-fat diet-induced NAFLD in rats, reduced the liver weight, lowered the TC, TG, LDL-c, AST, and ALT levels in serum(P<0.05), and rose the HDL-c level in serum(P<0.01). GPs relieved the liver damage caused by high-fat diet, mainly manifested by the lowered levels of TC, TG, MDA, and IL-6 in the liver(P<0.01) and elevated levels of CAT and SOD in the liver. Furthermore, GPs reversed the intestinal flora disorder caused by high-fat diet, restored the diversity of intestinal flora, increased the relative abundance of Bacteroides, and reduced the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroides. Moreover, GPs promoted the proliferation of beneficial bacteria such as Akkermansia, Bacteroides, and Parabacteroides, and inhibited the growth of harmful bacteria such as Desulfovibrio, Escherichia-Shigella, and Helicobacter. GPs increased the content of short-chain fatty acids(acetic acid, propionic acid, and butyric acid)(P<0.01). These findings indicate that GPs can alleviate the high-fat diet-induced NAFLD in rats via regulating the intestinal flora and short-chain fatty acid metabolism.

Research progress of intestinal microorganisms and pathogenesis of diabetes mellitus / 预防医学

Abstract@#As the largest human microecosystem, intestinal microorganisms participate in human material and energy metabolisms and pose a significant impact on human health. Diabetes mellitus is likely to cause imbalance of abundance and component alterations in intestinal microorganisms, and reduce the diversity and balance, leading to intestinal microflora dysregulation. It has been shown that intestinal microflora dysregulation may promote diabetes development and progression through the reduction of intestinal microbial metabolites, inflammatory reaction and insulin resistance. This review summarizes the involvement of intestinal microorganisms in the pathogenesis of diabetes through metabolites including short-chain fatty acid, bile acid and lipopolysaccharide, and describes the current status of intestinal microorganisms-mediated treatments for diabetes, so as to provide the theoretical basis for the researches on diabetes and intestinal microorganisms.

Regulatory effect of total phenolic acid from the stems and leaves of Salvia miltiorrhiza Bge. on intestinal microflora and short-chain fatty acids in type 2 diabetic nephropathy mice / 药学学报

To study the regulating effect of total phenolic acids from the stems and leaves of Salvia miltiorrhiza Bge. on the intestinal flora and short-chain fatty acids in spontaneous type 2 diabetic nephropathy mice, db/db mice were taken as the research object, and were treated with the total phenolic acid of Salvia miltiorrhiza Bge. Animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine Drug Safety Evaluation Research Center. Fresh feces and cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. Gas chromatography was used to detect short-chain fatty acids in fresh feces and cecal content. Then the correlation analysis of the two results was made. Compared with the normal group, the most significant decreased differential flora in the model group were g_Rikenellaceae_ RC9_gut_group and g_Bacteroidales_S24-7_group, while the most significant increased were g_unclassified_f__ Coriobacteriaceae and g_unclassified_p__Firmicutes. Compared with the blank group, the contents of isovaleric acid and valeric acid in fresh feces and the contents of 6 short-chain fatty acids in the cecal contents of the model group were significantly reduced (P < 0.01). After drug intervention, the intestinal flora disorder and the reduction of short-chain fatty acids were improved to varying degrees, and the effect of the total phenolic acids from the stems and leaves of Salvia miltiorrhiza Bge. was slightly better than that from the roots in regulating some flora and short-chain fatty acids. The results of correlation analysis showed that g_Rikenellaceae_RC9_gut_group was moderately positively correlated with acetic acid and isobutyric acid in the cecal contents (r > 0.4). It is suggested that the total phenolic acid from the stems and leaves of Salvia miltiorrhiza Bge. can improve the intestinal flora disorder of mice with type 2 diabetic nephropathy, and can regulate the content of short-chain fatty acids in the intestine via adjusting the content of some short-chain fatty acid-producing bacteria, thereby helping to restore normal.

Effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids in feces of very low birth weight infants: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids (SCFAs) in feces of very low birth weight (VLBW) infants.@*METHODS@#A total of 29 VLBW infants who were admitted to the Neonatal Diagnosis and Treatment Center of Children's Hospital Affiliated to Chongqing Medical University from June to December 2020 were enrolled as subjects for this prospective study. According to the course of treatment with broad-spectrum antibiotics, they were divided into two groups: ≤7 days (@*RESULTS@#There was a significant reduction in Chao index of the intestinal flora in the ≤7 days group and the >7 days group from week 2 to week 4 (@*CONCLUSIONS@#The course of treatment with broad-spectrum antibiotics can affect the abundance, colonization, and evolution of intestinal flora and the content of their metabolites SCFAs in VLBW infants. The indication and treatment course for broad-spectrum antibiotics should be strictly controlled in clinical practice.

Determination of medium- and short-chain fatty acids in feces by UHPLC-QTOF-MS/MS with pre-column derivatization / 药学学报

A pre-column derivatization and ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) method was developed for qualitative and quantitative determination of medium- and short-chain fatty acids in mice feces, and was further applied to evaluate variations in the feces of mice before and after antibiotic treatment. This animal experiment had been approved by Animal Experimental Ethics Committee of Jiangsu Province Academy of Traditional Chinese Medicine. By optimizing the derivatization conditions and UHPLC-QTOF-MS/MS parameters a new UHPLC-QTOF-MS/MS method with 3-nitrophenylhydrazine as the derivatization reagent was developed for simultaneous determination of 16 medium- and short-chain fatty acids. Validation studies showed that the linearity of the calibration curves was good (R2>0.99), the RSD of intra-day and inter-day precision was less than 10%, the repeatability RSD was less than 6%, the recovery rate was between 80% - 120% at three spiked levels, and the stability RSD was less than 7% within 36 h. The types and amounts of the detected medium- and short-chain fatty acids in feces significantly changed after the mice were treated with antibiotics. The content of formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and lactic acid decreased, whereas that of heptanoic acid and succinic acid increased significantly. All these results suggest that the newly established method is accurate and reliable, and can be used for determination of medium- and short-chain fatty acids in feces.

Short-chain Fatty Acids Inhibit Staphylococcal Lipoprotein-induced Nitric Oxide Production in Murine Macrophages

Staphylococcus aureus, a Gram-positive pathogen, can cause severe inflammation in humans, leading to various life-threatening diseases. The lipoprotein is a major virulence factor in S. aureus-induced infectious diseases and is responsible for excessive inflammatory mediators such as nitric oxide (NO). Short-chain fatty acids (SCFAs) including butyrate, propionate, and acetate are microbial metabolites in the gut that are known to have anti-inflammatory effects in the host. In this study, we investigated the effects of SCFAs on S. aureus lipoprotein (Sa.LPP)-induced NO production in mouse macrophages. Butyrate and propionate, but not acetate, inhibited Sa.LPP-induced production of NO in RAW 264.7 cells and bone marrow-derived macrophages. Butyrate and propionate inhibited Sa.LPP-induced expression of inducible NO synthase (iNOS). However, acetate did not show such effects under the same conditions. Furthermore, butyrate and propionate, but not acetate, inhibited Sa.LPP-induced activation of NF-κB, expression of IFN-β, and phosphorylation of STAT1, which are essential for inducing transcription of iNOS in macrophages. In addition, butyrate and propionate induced histone acetylation at lysine residues in the presence of Sa.LPP in RAW 264.7 cells. Moreover, Sa.LPP-induced NO production was decreased by histone deacetylase (HDAC) inhibitors. Collectively, these results suggest that butyrate and propionate ameliorate the inflammatory responses caused by S. aureus through the inhibition of NF-κB, IFN-β/STAT1, and HDAC, resulting in attenuated NO production in macrophages.

Effect of high fiber diet on activation and function of microglia in mouse brain / 解放军医学杂志

Objective To compare the levels of short-chain fatty acids produced by high-fiber diet and low-fiber diet in the intestinal metabolism of mice for exploring the effects of different fiber diets on the activation and function of microglia in mouse brain. Methods Mice fed with low-fiber and high-fiber diets were detected for the levels of three major short-chain fatty acids (acetic acid, propionic acid, butyrate) in the cecum. The distributions of microglia in the brain of different diet mice were compared by immunofluorescence. Real-time fluorescence quantitative PCR was used to detect expressions of genes associated with microglia activation in mouse brain between the above two groups of mice. Results The acetate level in the cecum of mice in high fiber diet group was higher than that of mice in low fiber diet group. There were no significant differences between the two groups in the levels of propionic acid and butyrate and the number and distribution of microglia. However, the levels of microglial activation-associated inflammatory cytokines such as IL-1β, IL-6, TNF-α, IL-12, CCL2, CCL5 and CCL7 mRNA were higher in high fiber diet group than in low fiber diet group after the intracranial stimulation by LPS. Conclusion The quantity of fiber in the diet after weaning can affect the maturation and activation of microglia in the brain, which may because of different levels of acetic acid after metabolism of different dietary structures by the intestinal flora.

Roles of short-chain fatty acids in kidney diseases / 中华医学杂志(英文版)

Objective:@#In kidney diseases, uncontrolled blood pressure, inflammation, oxidative stress, imbalanced immunity response, and metabolic dysfunction were associated with the progressive deterioration of renal function. Short-chain fatty acids (SCFAs), as a group of metabolites fermented by gut microbiota exerted regulatory effects on kidney diseases through their activation of transmembrane G protein-coupled receptors and their inhibition of histone acetylation. In this review article, we updated recent research advances that provided an opportunity to explore our understanding in physiology and function of SCFAs in kidney disease.@*Data sources:@#We performed a comprehensive search in both PubMed and Embase using "short-chain fatty acids" and "kidney" with no restrictions on publication date.@*Study selection:@#After reading through the title and abstract for early screening, the full text of relevant studies was identified and reviewed to summarize the roles of SCFAs in kidney diseases.@*Results:@#Though controversial, growing evidence suggested SCFAs appeared to have a complex but yet poorly understood communications with cellular and molecular processes that affected kidney function and responses to injury. From recent studies, SCFAs influenced multiple aspects of renal physiology including inflammation and immunity, fibrosis, blood pressure, and energy metabolism.@*Conclusions:@#The roles of intestinal SCFAs in kidney diseases were exciting regions in recent years; however, clinical trials and animal experiments in kidney diseases were still lacked. Thus, more research would be needed to obtain better understanding of SCFAs’ potential effects in kidney diseases.

Effects of Hericium erinaceus Polysaccharide on the Content of Short-chain Fatty Acids in the Intestine of Ulcerative Colitis Model Rats / 中国药房

OBJECTIVE： To investigate the effects of Hericium erinaceus polysaccharide on the content of short-chain fatty acids （SCFAs） in the intestine of ulcerative colitis model rats. METHODS： A total of 40 SD rats were randomly divided into blank group， model group and H. erinaceus polysaccharide low-dose and high-dose groups （0.5， 1.0 g/kg）， with 10 rats in each group. Except for blank group， other groups were given acetic acid enema to induce ulcerative colitis model. The next day after modeling， H. erinaceus polysaccharide groups were given relevant medicine solution intragastrically； blank group and model group were given relevant volume of water intragastrically， for 10 consecutive days. Colon tissue was collected， and pathological changes of colon tissue were observed by HE staining. The pathological changes of colon in rats were observed with naked eyes and scored so as to evaluate the therapeutic efficacy. The contents of 6 kinds of SCFAs （acetic acid，propionic acid，butyric acid，isobutyric acid，pentanoic acid and isovaleric acid） in intestine of rats were determined by GC-MS. RESULTS： Compared with blank group， inflammatory lesions of colonic mucosal epithelium in model group rats were obvious； colonic mucosal ulcer score increased significantly （P＜0.01）； the contents of 5 kinds of SCFAs and the total amount of SCFAs in colon except for propionic acid were decreased significantly （P＜0.01）. Compared with model group， the degree of colonic histopathological damage in H. erinaceus polysaccharide groups was significantly reduced； colonic mucosal ulcer scores were significantly reduced （P＜0.05 or P＜0.01）； the contents of 5 kinds of SCFAs and the total amount of SCFAs in colon except for propionic acid were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： H. erinaceus polysaccharide can effectively improve the pathological condition of ulcerative colitis model rats； its regulation of intestinal SCFAs （especially acetic acid and butyric acid） may be an important mechanism of its anti-ulcerative colitis.

Scientific research of laxative action of Cannabis Fructus based on intestinal environment adjustment / 中草药

Objective: To investigate the effects of the water extract of Cannabis Fructus on intestinal flora structure, short chain fatty acids (SCFAs) levels, and pathological changes of colonic inflammation, and explore its scientific connotation of laxative action. Methods: A total of 48 Wistar rats (SPF grade), sex in half, were randomly divided into control group, model group, Cannabis Fructus water extract group, and positive control group. The rats of model group were caused constipation and enteric flora disturbance by diphenoxylate. The bacterial counts in the fresh stool were tested by plate count method 28 days after administration, and the changes of intestinal flora structure in cecum was detected by PCR-DGGE method, the contents of SCFAs in cecum were determinated by GC method, and the coton pathological score of the rats were studied by HE staining method. Results: Compared with the blank group, the number of Escherichia coli and Bifidobacterium was increased but Bacillus acidi lactici was decreased significantly (P < 0.05, 0.01) in fresh stool of the model group. The ratio of Firmicutes bacteria to Bacteroides bacteria was increased, the number of Butyricicoccus and Cillobacterium was decreased, the concentration of acetic acid and butyric acid was increased significantly (P < 0.05, 0.01), and the pathology score of colon was increased significantly (P < 0.01). Compared with the model group, Cannabis Fructus water extract can adjust the ratio of Firmicutes bacteria to Bacteroides bacteria, increase the number of Cillobacterium, Butyricicoccus, Blautia, and Oscillibacter in cecum, decrease the number of Clostridium IV, etc., decrease the concentration of acetic acid and butyric acid (P < 0.05), reduce the pathology score, and improve the damage of intestinal structure (P < 0.05). Conclusion: Cannabis Fructus water extract can alleviate constipation and accelerate the recovery of colitis injury in model rats. The functional route of Cannabis Fructus water extract may relate to the disorder of intestinal flora balance adjustment and effect of the concentration of SCFAs so as to change the acidic environment in the intestinal tract.

Research progress of gut microbiota and microbiota-targeted therapy in critical ill patients / 中华危重病急救医学

In physiological conditions, a diverse microbiota might enhance host defense. However, the gut microbiota of critically ill patients is characterized by lower diversity, lower abundances of key commensal genera, and overgrowth by one bacterial generation, a state known as dysbiosis. Increasing evidences indicate that microbiota-derived components can reach the systemic circulation from the gut and modulate immune homeostasis. Dysbiosis could have greater consequences for the critically ill patients and might contribute to poor outcome. In this review, we highlighted the crucial role of intestinal microbiota in systemic homeostasis in the critically ill patients and summarized emerging evidence in the field of microbiota-targeted therapies. This would provide new perspective for further establishing the causes and consequences of dysbiosis found in the critically ill patients as well as developing new strategies of intervention.

An overview of biotechnological production of propionic acid: from upstream to downstream processes

The increasing demand for propionic acid (PA) production and its wide applications in several industries, especially the food industry (as a preservative and satiety inducer), have led to studies on the low-cost biosynthesis of this acid. This paper gives an overview of the biotechnological aspects of PA production and introduces Propionibacterium as the most popular organism for PA production. Moreover, all process variables influencing the production yield, different simple and complex carbon sources, the metabolic pathway of production, engineered mutants with increased productivity, and modified tolerance against high concentrations of acid have been described. Furthermore, possible methods of extraction and analysis of this organic acid, several applied bioreactors, and different culture systems and substrates are introduced. It can be concluded that maximum biomass and PA production may be achieved using metabolically engineered microorganisms and analyzing the most significant factors influencing yield. To date, the maximum reported yield for PA production is 0.973 g·g-1, obtained from Propionibacterium acidipropionici in a three-electrode amperometric culture system in medium containing 0.4 mM cobalt sepulchrate. In addition, the best promising substrate for PA bioproduction may be achieved using glycerol as a carbon source in an extractive continuous fermentation. Simultaneous production of PA and vitamin B12 is suggested, and finally, the limitations of and strategies for competitive microbial production with respect to chemical process from an economical point of view are proposed and presented. Finally, some future trends for bioproduction of PA are suggested.