Lipid-lowering and antioxidant effects of Polygonatum fermented liquor: a study on intestinal microbiota and brain-gut axis in mice.

Introduction: This study aims to investigate the effects of Polygonatum fermented liquor (PFL) on improving lipid metabolism and oxidative stress in mice by regulating the gut microbiota. Methods: Forty SPF-grade male Kunming mice were randomly divided into four groups: normal control group (NC), general liquor group (GC), fresh Polygonatum fermented liquor group (FPC), and nine-steam-nine-bask Polygonatum fermented liquor group (NPC). Each group was administered with sterile water, general liquor, fresh Polygonatum fermented liquor, and nine-steam-nine-bask Polygonatum fermented liquor, respectively, by gavage. The mice's liver, brain tissue, serum, and intestinal contents were collected. The indicators of oxidative stress in the liver, four blood lipid indicators, gamma-aminobutyric acid (GABA), and brain-derived neurotrophic factor (BDNF) levels in the brain tissue were measured, liver hematoxylin and eosin (HE) staining was performed, and the gut microbiota in the small intestine were analyzed using 16S rRNA second-generation sequencing technology. Results: Compared with the NC group, the NPC group showed significantly increased liver glutathione peroxidase (GSH-Px) content in mice (p < 0.05), reduced number of lipid droplets in the liver cells, and increased GABA and BDNF content in the brain tissues. The NPC group regulated lipid metabolism by lowering low-density lipoprotein cholesterol (LDL-C) and increasing high-density lipoprotein cholesterol (HDL-C) content in the mouse serum. Gut microbiota analysis showed significant changes in the gut microbiota of mice in the FPC and NPC groups, with increased richness and species diversity. These two groups increased the abundance of beneficial bacteria such as Lactobacillus, unclassified Muribaculaceae, unclassified Bacilli, and uncultured Bacteroidales bacterium while reducing the abundance of harmful bacteria such as Candidatus Arthromitus, and Staphylococcus, with a particularly significant reduction in Staphylococcus (p < 0.05). It is speculated that the two types of PFL may exert lipid-lowering and antioxidant effects by modulating the abundance of these dominant bacteria. Further studies showed that various environmental factors are closely related to the dominant gut bacteria. Malondialdehyde (MDA) was significantly negatively correlated with Lactobacillus and unclassified Bacilli, superoxide dismutase (SOD) was significantly negatively correlated with Staphylococcus (p < 0.01) and significantly negatively correlated with Candidatus Arthromitus (p < 0.05), and HDL-C was significantly negatively correlated with Staphylococcus and Facklamia (p < 0.05). Discussion: The two types of PFL chosen in this study may exert lipid-lowering and antioxidant effects by modulating the composition and function of the gut microbiota, providing guidance for the industrial application of Polygonatum.

Sishen Pill inhibits intestinal inflammation in diarrhea mice via regulating kidney-intestinal bacteria-metabolic pathway.

Background: Sishen Pill (SSP) has good efficacy in diarrhea with deficiency kidney-yang syndrome (DKYS), but the mechanism of efficacy involving intestinal microecology has not been elucidated. Objective: This study investigated the mechanism of SSP in regulating intestinal microecology in diarrhea with DKYS. Methods: Adenine combined with Folium sennae was used to construct a mouse model of diarrhea with DKYS and administered with SSP. The behavioral changes and characteristics of gut content microbiota and short-chain fatty acids (SCFAs) of mice were analyzed to explore the potential association between the characteristic bacteria, SCFAs, intestinal inflammatory and kidney function-related indicators. Results: After SSP intervention, the body weight and anal temperature of diarrhea with DKYS gradually recovered and approached the normal level. Lactobacillus johnsonii was significantly enriched, and propionic, butyric, isobutyric and isovaleric acids were elevated. Serum creatinine (Cr), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels of the mice were reduced, while serum blood urea nitrogen (BUN) and secretory immunoglobulin A (sIgA) in the colonic tissues were increased. Moreover, there were correlations between L. johnsonii, SCFAs, intestinal inflammatory, and kidney function. Conclusion: SSP might suppress the intestinal inflammation by regulating the "L. johnsonii-propionic acid" pathway, thus achieving the effect of treating diarrhea with DKYS.

Dysfunction of cecal microbiota and CutC activity in mice mediating diarrhea with kidney-yang deficiency syndrome.

Objective: Previous studies have indicated that diarrhea with kidney-yang deficiency syndrome leads to a disorder of small intestine contents and mucosal microbiota. However, the relationship of TMA-lyase (CutC) activity and TMAO with diarrhea with kidney-yang deficiency syndrome remains unexplored. Therefore, this study explores the relationship between cecal microbiota and choline TMA-lyase (CutC) activity, as well as the correlation between trimethylamine oxide (TMAO), inflammatory index, and CutC activity. Method: Twenty SPF-grade male KM mice were randomly divided into the normal group (CN) and the diarrhea model group (CD). Diarrhea mouse models were established by adenine combined with Folium sennae administration. CutC activity, TMAO, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were detected, and the cecal content microbiota was sequenced. Result: After 14 days, diarrhea occurred in the CD group. Compared with the CN group, there was no significant change in the activity of CutC in the small intestine of the CD group, while the activity of CutC in the cecum was significantly increased, and the levels of TMAO, IL-6, and TNF-α showed a significant increase. The Chao1 index, Observed_species index, Shannon index, and Simpson index all exhibited a decreasing trend. The main changes at the bacterial genus level were Alistipes, Enterorhabdus, Desulfovibrio, Bacteroides, Candidatus_Saccharimonas, and [Ruminococcus]_torques_group. The results of LEfSe analysis, random forest analysis and ROC curve analysis revealed Paludicola, Blautia, Negativibacillus, Paraprevotella, Harryflintia, Candidatus_Soleaferrea, Anaerotruncus, Oscillibacter, Colidextribacter, [Ruminococcus]_torques_group, and Bacteroides as characteristic bacteria in the CD group. Correlation analysis showed a significant negative correlation between cecal CutC activity and Ligilactobacillus, and a significant positive correlation with Negativibacillus and Paludicola. The level of TMAO was significantly positively correlated with CutC activity and IL-6. Conclusion: Diarrhea with kidney-yang deficiency syndrome significantly affects the physiological status, digestive enzyme activity, CutC activity, TMAO levels, and inflammatory response in mice. Additionally, there are changes in the composition and function of cecal microbiota, indicating an important impact of diarrhea with kidney-yang deficiency syndrome on the host intestinal microbiota balance. The occurrence of diarrhea with kidney-yang deficiency syndrome may be associated with dysbiosis of intestinal microbiota, increased CutC activity, elevated TMAO levels, and heightened inflammatory factor levels.

Adenine's impact on mice's gut and kidney varies with the dosage administered and relates to intestinal microorganisms and enzyme activities.

This study aimed to investigate the effects of different dosages of adenine on intestinal microorganisms and enzyme activities, laying the experimental groundwork for subsequent exploration of the microbial mechanisms underlying diarrhea with kidney yang deficiency syndrome. Twenty-four mice were assigned to the following four groups: the control (NC) group, low-dosage adenine (NML) group, middle-dosage adenine (NMM) group, and high-dosage adenine (NMH) group. Mice in the NML, NMM, and NMH groups received 25 mg/(kg·d), 50 mg/(kg·d), and 100 mg/(kg·d) of adenine, respectively, 0.4 mL/each, once a day for 14 days. The NC group received 0.4 mL sterile water. Parameters including body weight, rectal temperature, intestinal microorganisms, enzyme activities, and microbial activity were measured. Results indicated that mice in the experimental group displayed signs of a poor mental state, curled up with their backs arched, and felt sleepy and lazy, with sparse fur that was easily shed, and damp bedding. Some mice showed fecal adhesion contamination in the perianal and tail areas. Dosage-dependent effects were observed, with decreased food intake, body weight, rectal temperature, and microbial activity and increased water intake and fecal water content. Enzyme activity analyses revealed significantly higher activities of protease, sucrase, amylase, and cellulase in intestinal contents and lactase, sucrase, amylase, and cellulase in the mucosa of the NMM group compared to those of other groups. Ultimately, the higher adenine dosage was associated with more pronounced symptoms of kidney yang deficiency syndrome, with 50 mg/kg adenine exhibiting the most substantial impact on the number of intestinal microbial colonies and enzyme activities.

Rubus suavissimus S. Lee Extract Alleviates Oxidative Stress and Inflammation in H2O2-Treated Retinal Pigment Epithelial Cells and in High-Fat Diet-Fed Mouse Retinas.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of visual disorders in the aged population and is characterized by the formation of retinal pigment epithelium (RPE) deposits and dysfunction/death of the RPE and photoreceptors. It is supposed that both oxidative stress and inflammation play a critical role in the pathogenesis of AMD. The development of therapeutic strategies against oxidative stress and inflammation in AMD is urgently needed. Rubus suavissimus S. Lee (RS), a medicinal plant growing in the southwest region of China, has been used as an herbal tea and medicine for various diseases. METHODS: In this project, we evaluate the therapeutic potential of RS extract for AMD. We prepared RS extracts from dried leaves, which contained the main functional compounds. RESULTS: RS extract significantly increased cell viability, upregulated the expression of antioxidant genes, lowered the generation of malondialdehyde and reactive oxygen species, and suppressed inflammation in H2O2-treated human RPE cells. In the in vivo study, treatment with RS extract attenuated body weight gain, lowered cholesterol and triglyceride levels in the liver and serum, increased antioxidant capacity, and alleviated inflammation in the retina and RPE/choroid of mice fed a high-fat diet. CONCLUSIONS: Our findings suggest that RS extract offers therapeutic potential for treating AMD patients.

Diarrhea accompanies intestinal inflammation and intestinal mucosal microbiota dysbiosis during fatigue combined with a high-fat diet.

OBJECTIVE: It was reported fatigue or a high-fat diet triggers diarrhea, and intestinal microbiota may play central roles in diarrhea. Therefore, we investigated the association between the intestinal mucosal microbiota and the intestinal mucosal barrier from fatigue combined with a high-fat diet. METHOD: This study divided the Specific pathogen-free (SPF) male mice into the normal group (MCN) and the standing united lard group (MSLD). The MSLD group stood on water environment platform box for 4 h/day for 14 days, and 0.4 mL lard was gavaged from day 8, twice daily for 7 days. RESULT: After 14 days, Mice in the MSLD group showed diarrhea symptoms. The pathological analysis showed structural damage to the small intestine in the MSLD group, with an increasing trend of interleukin-6 (IL-6) and IL-17, and inflammation accompanied by structural damage to the intestine. Fatigue combined with a high-fat diet considerably decreased Limosilactobacillus vaginalis and Limosilactobacillus reuteri, and among them, Limosilactobacillus reuteri positively associated with Muc2 and negatively with IL-6. CONCLUSION: The interactions between Limosilactobacillus reuteri and intestinal inflammation might be involved in the process of intestinal mucosal barrier impairment in fatigue combined with high-fat diet-induced diarrhea.

The diarrheal mechanism of mice with a high-fat diet in a fatigued state is associated with intestinal mucosa microbiota.

Growing evidence has demonstrated that fatigue and a high-fat diet trigger diarrhea, and intestinal microbiota disorder interact with diarrhea. However, the association of intestinal mucosal microbiota with fatigue and high-fat diet trigger diarrhea remains unclear. The specific pathogen-free Kunming male mice were randomly divided into the normal group (MCN), standing group (MSD), lard group (MLD), and standing united lard group (MSLD). Mice in the MSD and MSLD groups stood on the multiple-platform apparatus for four h/d for fourteen consecutive days. From the eighth day, mice in the MLD and MSLD groups were intragastric lard, 0.4 mL/each, twice a day for seven days. Subsequently, we analyzed the characteristics and interaction relationship of intestinal mucosal microbiota, interleukin-6 (IL-6), interleukin-17 (IL-17), malondialdehyde (MDA), superoxide dismutase (SOD), and secretory immunoglobulin A (sIgA). Results showed that mice in the MSLD group had an increased number of bowel movements. Compared with the MCN group, the contents of IL-17, and IL-6 were higher (p > 0.05), and the content of sIgA was lower in the MSLD group (p > 0.05). MDA and SOD increased in MLD and MSLD groups. Thermoactinomyces and Staphyloccus were the characteristic bacteria of the MSLD group. And Staphyloccus were positively correlated with IL-6, IL-17, and SOD. In conclusion, the interactions between Thermoactinomyces, Staphyloccus and intestinal inflammation, and immunity might be involved in fatigue and high-fat diet-induced diarrhea.

Gut-Kidney Impairment Process of Adenine Combined with Folium sennae-Induced Diarrhea: Association with Interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and Acetic Acid, Inflammation, and Kidney Function.

BACKGROUND: Extensive evidence suggests that gut microbiota may interact with the kidneys and play central roles in the pathogenesis of disease. However, the association of gut microbiota-kidneys in diarrhea remains unclear. METHODS: A diarrhea mouse model was constructed by combining adenine with Folium sennae. We analyzed the characteristics of the gut content microbiota and short chain fatty acids (SCFAs); and explored the potential link between gut content microbiota, SCFAs, intestinal inflammatory response and kidney function. RESULTS: Characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens were enriched in the gut contents of mice. The productions of SCFAs were remarkably inhibited. Model mice presented an increased trend of creatinine (Cr), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), a decreased trend of blood urea nitrogen (BUN) and secretory immunoglobulin A (SIgA). The pathological analysis proved obvious damage to the kidney structure. Lactobacillus intestinalis and Bacteroides acidifaciens exisited in the correlations with acetic acid, intestinal inflammatory response and kidney function. CONCLUSIONS: Adenine combined with Folium sennae-induced diarrhea, altered the structure and function of the gut content microbiota in mice, causing the enrichment of the characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens. The interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and acetic acid, intestinal inflammation, and kidney function might be involved in the process of gut-kidney impairment in adenine, combined with Folium sennae-induced diarrhea.

Comparative Analysis of the Gut Microbiota in Mice under Lard or Vegetable Blend Oil Diet.

Diet is the most direct and rapid contributor to the gut microbiome. Oils and fats are important nutrients in the human body. The effects of lard or vegetable blend oil on gut microbiota were investigated. Kunming mice were given lard or vegetable blend oil for six weeks. Changes in microbiota composition and abundance in lard or vegetable blend oil diets were analyzed by 16S rRNA gene amplicon sequencing. Our study shows that the gut microbiota of mice changed significantly after ingestion of lard or vegetable blend oil. Lard may synergize with Coriobacteriaceae_UCG-002. Vegetable blend oil has synergistic effects with Akkermansia, Roseburia, and Enteractinococcus. Coriobacteriaceae_UCG-002 showed a significant negative correlation with Glycolysis/Gluconeogenesis. Roseburia was most strongly associated with Starch and sucrose metabolism. According to bacterial function prediction and correlation analysis, long-term consumption of lard or vegetable oil may affect glycolipid metabolism, but lard has a greater impact on human health and consequently host health.

Bioinformatical and Biochemical Analyses on the Protective Role of Traditional Chinese Medicine against Age-Related Macular Degeneration.

PURPOSE: Age-related macular degeneration (AMD) is the commonest cause of permanent vision loss in the elderly. Traditional Chinese medicine (TCM) has long been used to treat AMD, although the underlying functional mechanisms are not understood. This study aims to predict the active ingredients through screening the chemical ingredients of anti-AMD decoction and to elucidate the underlying mechanisms. METHODS: We collected the prescriptions for effective AMD treatment with traditional Chinese medicine and screened several Chinese medicines that were used most frequently in order to compose "anti-AMD decoction." The pharmacologically active ingredients and corresponding targets in this anti-AMD decoction were mined using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the AMD-related targets were identified through the GeneCards database. Network pharmacology was performed to construct the visual network of anti-AMD decoction-AMD protein-protein interaction (PPI). Further, the Autodock software was adopted for molecular docking on the core active ingredients and core targets. The function of core ingredients against oxidative stress and inflammation in retinal pigment epithelial cells was assessed using biochemical assays. RESULTS: We screened out 268 active ingredients in anti-AMD decoction corresponding to 258 ingredient targets, combined with 2160 disease targets in AMD, and obtained 129 drug-disease common targets. The key core proteins were predominantly involved in inflammation. Furthermore, molecular docking showed that four potential active ingredients (Quercetin, luteolin, naringenin and hederagenin) had good affinity with the core proteins, IL-6, TNF, VEGFA and MAPK3. Quercetin, luteolin and naringenin demonstrated capacities against oxidative stress and inflammation in human retinal pigment epithelial cells. CONCLUSIONS: The data suggests that anti-AMD decoction has multiple functional components and targets in treating AMD, possibly mediated by suppression of oxidative stress and inflammation.

Association of Nutrients, Specific Dietary Patterns, and Probiotics with Age-related Macular Degeneration.

Age-related macular degeneration (AMD) is a complex disease that mainly affects people over 50 years of age. Even though management of the vascularisation associated with the "wet" form of AMD is effective using anti-VEGF drugs, there is currently no treatment for the "dry" form of AMD. Given this, it is imperative to develop methods for disease prevention and treatment. For this review, we searched scientific articles via PubMed and Google Scholar, and considered the impact of nutrients, specific dietary patterns, and probiotics on the incidence and progression of AMD. Many studies revealed that regular consumption of foods that contain ω-3 fatty acids is associated with a lower risk for late AMD. Particular dietary patterns, such as the Mediterranean diet that contains ω-3 FAs-rich foods (nuts, olive oil, and fish), seem to be protective against AMD progression compared to Western diets that are rich in fats and carbohydrates. Furthermore, randomized controlled trials that investigated the role of nutrient supplementation in AMD have shown that treatment with antioxidants, such as lutein/zeaxanthin, zinc, and carotenoids, may be effective against AMD progression. More recent studies have investigated the association of the antioxidant properties of gut bacteria, such as Bacteroides and Eysipelotrichi, with lower AMD risk in individuals whose microbiota is enriched with them. These are promising fields of research that may yield the capacity to improve the quality of life for millions of people, allowing them to live with a clear vision for longer and avoiding the high cost of vision-saving surgery.

Trans-urocanic acid facilitates spatial memory, implications for Alzheimer's disease.

Trans-urocanic acid (trans-UCA) is an isomer of cis-UCA and is widely distributed in the brain, predominantly in the hippocampus and prefrontal cortex. Previous studies have investigated the role of trans-UCA in non-spatial memory; however, its influence on spatial memory remains unclear. In the present study, network pharmacology strategy and behavioral testing were used to evaluate the role of trans-UCA in spatial memory and predict its possible mechanism. The results showed that there are 40 intersecting targets between trans-UCA and spatial memory identified by several databases and Venn diagram, indicating that trans-UCA may be involved in spatial memory. Behavioral results show that trans-UCA facilitates spatial working memory in the Y-maze test as well as spatial recognition memory acquisition, consolidation and retrieval in an object location recognition (OLR) task. Furthermore, PPI (protein-protein interaction) network analysis, GO (gene ontology) and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses show that the molecular mechanisms underlying the enhancing effect of trans-UCA on spatial memory are mainly associated with the regulation of insulin, mitogen-activated protein kinase (MAPK) and nuclear factor Kappa B (NF-κB) signaling pathways, serotonergic synapse and arginine and proline metabolism. The results of this study suggest that trans-UCA facilitates spatial memory in the Y-maze test and OLR task and may offer therapeutic potential for Alzheimer's disease (AD). The underlying mechanisms predicted by network pharmacology should be further verified.

Different Effects of Lard and Vegetable Blend Oil on Intestinal Microorganisms, Enzyme Activity and Blood Routine in Mice.

The intake of moderate oils and fats is necessary to maintain the body's energy balance, and the fatty acid composition of different oils and fats varies in their nutrition and function. The study aimed to investigate the effects of lard and vegetable blend oil on gut microbiota, intestinal enzyme activities, and blood routine. Kunming mice were assigned to the three groups: (1) Control group (CK) was gavage administration with distilled water, (2) Plant oil group (ZWY) was gavage administration with edible vegetable blend oil, (3) Lard group (DWY) was gavage administration with lard. After 42 days, microbiological, digestive enzymes, and blood routine were performed. Compared with the CK group, Escherichia coli, Lactobacilli, and Bifidobacteria were significantly decreased (p < 0.05), the activities of protease, cellulase, amylase, and xylanase were markedly reduced (p < 0.05), the hemoglobin was significantly increased (p < 0.05) in the ZWY group and DWY groups, and the hematocrit was increased in the ZWY group (p < 0.05), while other routine blood indices were increased (p > 0.05). Compared to the ZWY group, the activity of cellulase and amylase were significantly increased (p < 0.05), the intestinal microorganism and the routine blood indexes had no significant difference in the DWY group. Lard and vegetable blend oil diet affected the composition of the intestinal microorganisms, and the functions of digestive enzymes. Meanwhile, the levels of digestive enzymes may be correlated with the intestinal microbiota.

Effect of Gegenqinlian decoction on intestinal mucosal flora in mice with diarrhea induced by high temperature and humidity treatment.

The objective of this study is to investigate the regulation effects of the active ingredients in Gegenqinlian Decoction (GD) on the intestinal mucosal flora of mice with diarrhea induced by high temperature and humidity based on systems pharmacology approach. Fifteen mice were randomly assigned to three equal groups of five mice, namely control (ctcm) group, model (ctmm) group and treatment (cttm) group. Mice in the cttm group were given 20 mL/kg of GD and sterile water was used as a placebo control twice a day for four consecutive days. We used the third-generation molecular high-throughput sequencing technology to measure the intestinal mucosal flora changes in mice. Combined with network pharmacology to predict the medicinal substances and action targets of GD against diarrhea. Results showed that Operational Taxonomic Unit (OTU) number and Alpha diversity in the intestinal mucosal flora of cttm group recovered and higher than that of the ctcm group. There were differences in the community structure between the ctmm and cttm groups in the Principal Coordinates Analysis (PCoA). The relative abundance results indicated dominant bacteria species (such as Lactobacillus crispatus, Muribaculum intestinal, Neisseria mucosa) in the intestinal mucosa of the three groups. Moreover, we screened out 146 active ingredients in GD corresponding to 252 component targets, and 328 disease targets in diarrhea to obtain 31 drug-disease common targets. Protein-protein interaction (PPI) networks mainly involved the core proteins such as Tumor necrosis factor (TNF) and Interleukin-6 (IL-6). Enrichment analyses showed that GD played a role in the treatment of diarrhea by regulating the hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF) and adipocytokine signaling pathways and so on. In brief, the active ingredients of GD could intervene from oxidative stress and inflammatory response through multiple targets and multiple channels to adjust the balance of intestinal mucosa flora, thereby playing a role in the treatment of diarrhea. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-020-02628-0.

Intestinal mucosal bacterial diversity of antibiotic-associated diarrhea (AAD) mice treated with Debaryomyces hansenii and Qiweibaizhu powder.

The aim was to investigate the combined effect of Debaryomyces hansenii and Qiweibaizhu powder (QWBZP) on the bacterial diversity of the intestinal mucosa of antibiotic-associated diarrhea (AAD) mice, for the potential treatment of diarrhea, especially which is induced by administration of antibiotics. Eighteen (18) mice were randomly assigned to three equal groups of six mice, namely Normal (mn group), Placebo control (mm group) and D. hansenii and QWBZP (DQ) treatment (mdq group). Mice were gavaged with a solution (23.33 mL·kg-1·day-1) consisting of gentamicin and cefradine to establish AAD. The DQ treatment group was gavaged with DQ for 4 days, and sterile water was used as a placebo control. The metagenome DNA of the intestinal mucosal microbiota was extracted, and the 16S rRNA gene was sequenced. Analysis showed that there were 288 OTUs for the normal group, 443 for the placebo control group, and 229 for the DQ treatment group. Phylogenetically, the gut microbiota of the DQ treatment group and the normal group were closer to each other than to the placebo control group. Both the DQ and placebo-treated groups included Stenotrophomonas, Robinsoniella, Bacteroidales S24-7 group norank, Citrobacter, and Glutamicibacter, but their abundances were significantly higher in the DQ treatment group than in the placebo control group. This suggested that the combined use of D. hansenii and QWBZP overcame the influence of dysbacteriosis and could lead to the recovery of intestinal mucosal microbiota homeostasis. This positive effect is likely related to short-chain fatty acid (SCFA)-producing bacteria, such as members of Micrococcaceae, Lachnospiraceae, and Bacteroidales S24-7 group, which could play beneficial roles in protecting the mucosal barrier and stimulating the immune response in mice.

Bacterial diversity in intestinal mucosa of antibiotic-associated diarrhea mice.

To probe into the mechanism of antibiotic-associated diarrhea (AAD), the bacterial diversity and composition in the intestinal mucosa of AAD mice were investigated. Twelve specific pathogen-free Kunming mice were divided into control group and model group. The mouse model of AAD was established by gavaging with antibiotics (mixture of gentamycin sulfate and cefradine) at a total dose of 23.33 ml kg-1 day-1 for 5 days continuously, twice a day. The mice in the control group were given with an equal amount of sterile water. Then, the intestinal mucosa DNA was extracted for 16S rRNA gene sequence analysis by high-throughput sequencing. The results showed that the alpha diversity of the two groups did not differ significantly from each other, while the composition of intestinal mucosa bacteria differed dramatically between the two groups. The model group showed a higher abundance of Proteobacteria and Actinobacteria. More importantly, Lactobacillus was significantly less abundant (p = 0.000), while Enterococcus was significantly more abundant (p = 0.019) in the model group than in the control group. Furthermore, antibiotic treatment increased the abundance of Citrobacter, Stenotrophomonas, and Glutamicibacter,whereas antibiotics decreased the abundance of Mycoplasma and Helicobacter. In addition, 6 and 11 unique genera were found in the control group and model group, respectively. The combination of gentamycin sulfate and cefradine changed the intestinal mucosa bacterial composition, reduced colonization resistance and damaged the intestinal mucosal barrier by reducing the abundance of Lactobacillus.

Effects of Debaryomyces hansenii treatment on intestinal microorganisms in mice with antibiotics-induced diarrhea.

To investigate the influence of Debaryomyces hansenii treatment on intestinal microorganisms in mice with antibiotics-induced diarrhea, mouse model of antibiotics-induced diarrhea was created by gavaging mice with mixed antibiotics (23.33 mL/kg/days) composed of gentamycin sulfate and cefradine for 5 days. Mice with the symptom of diarrhea were then treated with D. hansenii by intragastric administration. The control group mice were given with sterile water. After 4 day treatment, total DNA of intestinal microflora of treated and control mice was extracted, and their quantities were measured by sequencing the V4 region of 16S rDNA. The results showed that when compared to the control (sterile water), treatment with D. hansenii increased the operational taxonomic units (OTUs) of intestinal bacteria. The Chao index in diarrhea treated group was higher than diarrhea control group and was similar to healthy control group, while all differences had no significance (P > 0.05). D. hansenii treatment increased the Shannon index but not significantly (P > 0.05). Moreover, there was not significant impact on density and diversity of intestinal bacterial population at phylum and genus levels (P > 0.05). Interestingly, D. hansenii treatment recovered the population density of certain bacterium species, such as Bacteroidaceae (in family level) (P < 0.05). Our results indicate that D. hansenii has potency of adjusting the density and diversity of intestinal bacteria and recovering the population density of Bacteroidaceae in family level.