1.Jujubae Fructus alleviates intestinal injury caused by toxic medicinals in Shizao Decoction based on correlation between intestinal flora and host metabolism.
Xiao-Qin GAO ; Jin-di XU ; Shi-Kang ZHOU ; Yi ZHANG ; Li ZHANG
China Journal of Chinese Materia Medica 2023;48(10):2792-2802
Genkwa Fols, Kansui Radix, and Euphorbiae Pekinensis Radix in Shizao Decoction(SZD) are toxic to intestinal tract. Jujubae Fructus in this prescription can alleviate the toxicity, but the mechanism is still unclear. Therefore, this study aims to explore the mechanism. To be specific, 40 normal Sprague-Dawley(SD) rats were classified into the normal group, high-dose and low-dose SZD groups, and high-dose and low-dose SZD without Jujubae Fructus(SZD-JF) groups. The SZD groups were given(ig) SZD, while SZD-JF groups received the decoction without Jujubae Fructus. The variation of body weight and spleen index were recorded. The patho-logical changes of intestinal tissue were observed based on hematoxylin and eosin(HE) staining. The content of malondialdehyde(MDA) and glutathione(GSH) and activity of superoxide dismutase(SOD) in intestinal tissue were measured to evaluate the intestinal injury. Fresh feces of rats were collected to detect intestinal flora structure by 16S ribosomal RNA gene(16S rDNA) sequencing technology. The content of fecal short chain fatty acids and fecal metabolites was determined by gas chromatography-mass spectrometer(GC-MS) and liquid chromatography-mass spectrometer ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometer(UFLC-Q-TOF-MS), separately. Spearman's correlation analysis was employed to analyze the differential bacteria genera and differential metabolites. RESULTS:: showed that high-dose and low-dose SZD-JF groups had high content of MDA in intestinal tissue, low GSH content and SOD activity, short intestinal villi(P<0.05), low diversity and abundance of intestinal flora, variation in the intestinal flora structure, and low content of short chain fatty acids(P<0.05) compared with the normal group. Compared with high-dose and low-dose SZD-JF groups, high-dose and low-dose SZD groups displayed low content of MDA in intestinal tissue, high GSH content and SOD activity, recovery of the length of intestinal villi, increased abundance and diversity of intestinal flora, alleviation of dysbacteria, and recovery of the content of short chain fatty acids(P<0.05). According to the variation of intestinal flora and fecal metabolites after the addition of Jujubae Fructus, 6 differential bacterial genera(Lactobacillus, Butyricimonas, Clostridia_UCG-014, Prevotella, Escherichia-Shigella, Alistipes),4 differential short chain fatty acids(such as acetic acid, propionic acid, butyric acid, valeric acid) and 18 differential metabolites(such as urolithin A, lithocholic acid, and creatinine) were screened out. Beneficial bacteria such as Lactobacillus were in positive correlation with butyric acid and urolithin A(P<0.05). The pathogenic bacteria such as Escherichia-Shigella were in negative correlation with propionic acid and urolithin A(P<0.05). In summary, SZD-JF caused obvious intestinal injury to normal rats, which could lead to intestinal flora disorder. The addition of Jujubae Fructus can alleviate the disorder and relieve the injury by regulating intestinal flora and the metabolites. This study discusses the effect of Jujubae Fructus in relieving the intestinal injury caused by SZD and the mechanism from the perspective of intestinal flora-host metabolism, which is expected to serve as a reference for clinical application of this prescription.
Rats
;
Animals
;
Rats, Sprague-Dawley
;
Propionates/pharmacology*
;
Gastrointestinal Microbiome
;
Fatty Acids, Volatile/pharmacology*
;
Butyrates/pharmacology*
2.Research progress of Eubacterium and its metabolite short-chain fatty acids in regulating type 2 diabetes mellitus.
Wei Dong LI ; Li Sha LI ; Mei Jun LYU ; Qiong Ying HU ; Da Qian XIONG
Chinese Journal of Preventive Medicine 2023;57(1):120-124
Intestinal flora and its metabolites are closely related to the progression of type 2 diabetes mellitus(T2DM). Eubacterium is one of the dominant intestinal flora, and its metabolites short-chain fatty acids (SCFAs) play a leading role in regulating intestinal metabolic balance. It has been reported that SCFAs can regulate the secretion of glucagon-like peptide-1, improve the function of pancreatic β cells, participate in bile acids metabolism and regulate the production of inflammatory factors in T2DM. Based on the above research background, this article mainly reviews the relationship between Eubacterium and its metabolite SCFAs and T2DM and its regulatory mechanism.
Humans
;
Diabetes Mellitus, Type 2
;
Eubacterium/metabolism*
;
Fatty Acids, Volatile/metabolism*
;
Gastrointestinal Microbiome
3.Effects of electroacupuncture at "Siguan" points on the expression of colonic 5-hydroxytryptamine and fecal short-chain fatty acids in rats with post-stroke depression.
Hui XU ; Lian-Qiu LI ; Zhen KANG ; Zhuang-Zhi CHEN ; Pei-Yi LIN ; Ling-Lang FANG ; Peng ZHANG ; Hai-Min YE
Chinese Acupuncture & Moxibustion 2023;43(5):545-551
OBJECTIVE:
To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD.
METHODS:
Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg-1•d-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg-1•d-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry.
RESULTS:
After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004).
CONCLUSION
Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.
Animals
;
Rats
;
Rats, Sprague-Dawley
;
Propionates
;
Serotonin
;
Depression/therapy*
;
Electroacupuncture
;
Fatty Acids, Volatile
;
Stroke/complications*
;
Acetic Acid
;
Butyric Acid
;
Water
4.Metagenomic and targeted metabolomic analyses reveal distinct phenotypes of the gut microbiota in patients with colorectal cancer and type 2 diabetes mellitus.
Yong YANG ; Zihan HAN ; Zhaoya GAO ; Jiajia CHEN ; Can SONG ; Jingxuan XU ; Hanyang WANG ; An HUANG ; Jingyi SHI ; Jin GU
Chinese Medical Journal 2023;136(23):2847-2856
BACKGROUND:
Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear.
METHODS:
We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups.
RESULTS:
Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga .
CONCLUSIONS
Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.
Humans
;
Gastrointestinal Microbiome/genetics*
;
Diabetes Mellitus, Type 2
;
Microbiota
;
Bacteria/genetics*
;
Fatty Acids, Volatile
;
Colorectal Neoplasms/metabolism*
;
Butyrates
;
Feces/microbiology*
5.Halomonas uses short-chain fatty acids to synthesize polyhydroxyalkanoates.
Wenguang CHEN ; Zihe LIU ; Zhengjun LI
Chinese Journal of Biotechnology 2022;38(4):1527-1536
Halomonas can grow on diverse carbon sources. As it can be used for unsterile fermentation under high-salt conditions, it has been applied as a chassis for next-generation industrial biotechnology. Short-chain volatile fatty acids, including acetate, propionate, and butyrate, can be prepared from biomass and are expected to be novel carbon sources for microbial fermentation. Halomonas sp. TD01 and TD08 were subjected to shaking culture with 10-50 g/L butyrate, and they were found to effectively synthesize poly-3-hydroxybutyrate with butyrate as the carbon source. The highest yield of poly-3-hydroxybutyrate was achieved at butyrate concentration of 20 g/L (9.12 g/L and 7.37 g/L, respectively). Butyrate at the concentration > 20 g/L inhibited cell growth, and the yield of poly-3-hydroxybutyrate decreased to < 4 g/L when butyrate concentration was 50 g/L. Moreover, Halomonas sp. TD08 can accumulate the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate by using propionate and butyrate as carbon sources. However, propionate was toxic to cells. To be specific, when 2 g/L propionate and 20 g/L butyrate were simultaneously provided, cell dry weight and polymer titer were 0.83 g/L and 0.15 g/L, respectively. The addition of glycerol significantly improved cell growth and boosted the copolymer titer to 3.95 g/L, with 3-hydroxyvalerate monomer content of 8.76 mol%. Short-chain volatile fatty acids would be promising carbon sources for the production of polyhydroxyalkanoates by Halomonas.
Butyrates
;
Carbon
;
Fatty Acids, Volatile
;
Halomonas
;
Polyhydroxyalkanoates
;
Propionates
6.Influence of enteral feeding initiation time on intestinal flora and metabolites in very low birth weight infants: a prospective study.
Yu-Jie SHEN ; Lu-Quan LI ; Lu WEI ; Xian-Hong ZHANG ; Wen-Jing ZHAO ; Xiao-Chen LIU ; Li-Ping WU
Chinese Journal of Contemporary Pediatrics 2022;24(4):433-439
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.
Child
;
Enteral Nutrition/methods*
;
Fatty Acids, Volatile
;
Gastrointestinal Microbiome
;
Humans
;
Infant
;
Infant, Newborn
;
Infant, Very Low Birth Weight
;
Propionates
;
Prospective Studies
7.Research Progress of Short Chain Fatty Acids in the Pathogenesis of Immune Thrombocytopenia--Review.
Journal of Experimental Hematology 2022;30(4):1296-1300
The gut microbiota is an important part of the human body, and it's also the largest genome in the human body. Recent studies on the gut microbiota have found that it plays an important role in human immune diseases. In recent years, the methods of sequencing gut microbiota has teen improved, thus dysregulation of the gut microbiota is found in many immune diseases, and the most widely studied mechanism is the short-chain fatty acids (SCFA), which is a metabolite of gut microbiota. The role of short-chain fatty acids in intestinal barrier, IgA immunity, dendritic cells and regulatory T cells has become increasingly clear. The mechanisms of short-chain fatty acids in regulating immunity and its role in the pathogenesis of immune thrombocytopenia were covered in this review, so as to provide a new idea for the treatment of immune thrombocytopenia in the future.
Adolescent
;
Fatty Acids, Volatile/metabolism*
;
Gastrointestinal Microbiome
;
Humans
;
Intestines
;
Purpura, Thrombocytopenic, Idiopathic
8.Short-chain fatty acid butyrate acid attenuates atherosclerotic plaque formation in apolipoprotein E-knockout mice and the underlying mechanism.
Hong-Bo BAI ; Ping YANG ; Han-Bin ZHANG ; Yu-Lin LIU ; Shu-Xiang FANG ; Xiao-Yang XU
Acta Physiologica Sinica 2021;73(1):42-50
This study was designed to evaluate the role of short-chain fatty acid butyrate acid on intestinal morphology and function, and atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE
Animals
;
Apolipoproteins E/genetics*
;
Atherosclerosis/prevention & control*
;
Butyrates/pharmacology*
;
Caco-2 Cells
;
Diet, High-Fat/adverse effects*
;
Fatty Acids, Volatile
;
Humans
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Plaque, Atherosclerotic
9.A review on polyhydroxyalkanoates synthesis in activated sludge system: the effects of dissolved organic compounds by using anaerobic fermentation liquid from waste activated sludge.
Jinyun DONG ; Fang FANG ; Jialing ZHANG ; Runze XU ; Jiayu WENG ; Jiashun CAO
Chinese Journal of Biotechnology 2021;37(1):149-162
Polyhydroxyalkanoates (PHA) synthesis by activated sludge using volatile fatty acids (VFAs) in fermentation liquid of excess sludge as carbon source is a hotspot in the field of environmental biotechnology. However, there is no unified conclusion on the effects of non-VFAs, mainly dissolved organic matter (DOM), on PHA production. Thus, this critical review mainly introduces the main characteristics and common analysis methods of DOM in anaerobic fermentation liquid. The effects of DOM on PHA production are analyzed from the aspects of microbiology, metabolic regulation and sludge properties. The results of different studies showed that high concentration of DOM is bad for PHA production, but an appropriate amount of DOM is conducive to the stability of sludge properties, reducing the final PHA purification cost. Finally, suitable strategies were proposed to regulate the PHA synthesis by activated sludge with DOM for PHA production by anaerobic fermentation liquid.
Anaerobiosis
;
Bioreactors
;
Fatty Acids, Volatile
;
Fermentation
;
Polyhydroxyalkanoates
;
Sewage
10.Co-fermentation of kitchen waste and excess sludge for organic acid production: a review.
Xuwei GUI ; Yifang LUO ; Zhenlun LI ; Ming NIE ; Yuran YANG ; Can ZHANG ; Jing LIU
Chinese Journal of Biotechnology 2021;37(2):448-460
Resource utilization is an effective way to cope with the rapid increase of kitchen waste and excess sludge, and volatile fatty acids produced by anaerobic fermentation is an important way of recycling organic waste. However, the single substrate limits the efficient production of volatile fatty acids. In recent years, volatile fatty acids produced by anaerobic co-fermentation using different substrates has been widely studied and applied. In this paper, we analyze the characteristics of fermentation to produce acid using kitchen waste and excess sludge alone or mixture. Influences of environmental factors and microbial community structure on the type and yield of volatile fatty acids in the anaerobic fermentation system are discussed in detail. Moreover, we propose future research directions, to provide a reference for recycling kitchen waste and excess sludge.
Anaerobiosis
;
Bioreactors
;
Fatty Acids, Volatile
;
Fermentation
;
Hydrogen-Ion Concentration
;
Microbiota
;
Organic Chemicals
;
Sewage

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