Composition Of Intestinal Bacteria Research Articles

Effects of bile acids on the growth, composition and metabolism of gut bacteria

Bile acids (BAs) exert a profound influence on the body’s pathophysiology by intricately shaping the composition of gut bacteria. However, the complex interplay between BAs and gut microbiota has impeded a systematic exploration of their impact on intestinal bacteria. Initially, we investigated the effects of 21 BAs on the growth of 65 gut bacterial strains in vitro. Subsequently, we examined the impact of BAs on the overall composition of intestinal bacteria, both in vivo and in vitro. The results unveiled distinct effects of various BAs on different intestinal strains and their diverse impacts on the composition of gut bacteria. Mechanistically, the inhibition of intestinal strains by BAs occurs through the accumulation of these acids within the strains. The intracellular accumulation of deoxycholic acid (DCA) significantly influenced the growth of intestinal bacteria by impacting ribosome transcription and amino-acid metabolism. The metabolomic analysis underscores the pronounced impact of DCA on amino-acid profiles in both in vivo and in vitro settings. This study not only elucidates the effects of BAs on a diverse range of bacterial strains and their role in shaping the gut microbiota but also reveals underlying mechanisms essential for understanding and maintaining a healthy gut microbiota.

Effect of Cotesia ruficrus Parasitization on Diversity and Community Composition of Intestinal Bacteria in Spodoptera frugiperda.

Parasitoids have the potential to alter the gut microbiota of their host insects post-parasitization, thereby influencing the host's physiological functions and creating a more favorable environment for the survival of the parasitoid's progeny. Cotesia ruficrus is a native enemy of the important invasive fall armyworm (FAW) pest, Spodoptera frugiperda, in China, exhibiting significant pest control capabilities. To investigate the impact of C. ruficrus on the gut bacteria of FAW caterpillars following parasitism, we used 16S rRNA sequencing technology to analyze the diversity and richness of gut bacteria in both long-term laboratory and short-term laboratory FAW caterpillars. The results revealed Enterococcus as the predominant bacteria across all treatments, while no significant differences were observed in the diversity and richness of gut bacteria between non-parasitized and parasitized long-term laboratory FAW caterpillars. Similarly, while the diversity of gut bacteria in non-parasitized and parasitized short-term laboratory FAWs showed no significant variance, a marked discrepancy in richness was noted. Moreover, the richness of gut bacteria in short-term laboratory FAW caterpillars surpassed that of their long-term laboratory counterparts. In addition, it was found that Corynebacterium existed only in the intestinal tract of FAW caterpillars that were parasitized by C. ruficrus. These results substantiate that C. ruficrus parasitization can alter the gut microbiota of FAW caterpillars, providing valuable insights into the interplay between gut microbiota and the dynamics of parasitoid-host interactions.

Exploring Scopoletin's Therapeutic Efficacy in DSS-Induced Ulcerative Colitis: Insights into Inflammatory Pathways, Immune Modulation, and Microbial Dynamics.

This study aimed to investigate the therapeutic potential of scopoletin in ulcerative colitis, with a primary focus on its impact on crucial inflammatory pathways and immune responses. A male mouse model of DSS-induced colitis was employed with six distinct groups: a control group, a group subjected to DSS only, three groups treated with varying scopoletin doses, and the final group treated with dexamethasone. The investigation included an assessment of the effects of scopoletin on colitis symptoms, including alterations in body weight, Disease Activity Index (DAI), and histopathological changes in colonic tissue. Furthermore, this study scrutinized the influence of scopoletin on cytokine production, PPARγ and NF-κB expression, NLRP3 inflammasome, and the composition of intestinal bacteria. Scopoletin treatment yielded noteworthy improvements in DSS-induced colitis in mice, as evidenced by reduced weight loss and colonic shortening (p < 0.05, < 0.01, respectively). It effectively diminished TNF-α, IL-1β, and IL-12 cytokine levels (p < 0.01, p < 0.05), attenuated NLRP3 inflammasome activation and the associated cytokine release (p < 0.05, p < 0.01), and modulated the immune response by elevating PPARγ expression while suppressing NF-κB pathway activation (p < 0.05, p < 0.01). Additionally, scopoletin induced alterations in the gut microbiota composition, augmenting beneficial Lactobacillus and Bifidobacteria while reducing E. coli (p < 0.05). It also enhanced tight junction proteins, signifying an improvement in the intestinal barrier integrity (p < 0.05, < 0.01). Scopoletin is a promising therapeutic agent for managing ulcerative colitis, showing benefits that extend beyond mere anti-inflammatory actions to encompass regulatory effects on gut microbiota and restoration of intestinal integrity.

Analysis of Alterations in Intestinal Flora in Chinese Elderly with Cardiovascular Disease and Its Association with Trimethylamine.

To investigate the changes in the intestinal flora in the Chinese elderly with cardiovascular disease (CVD) and its correlation with the metabolism of trimethylamine (TMA), the intestinal flora composition of elderly individuals with CVD and healthy elderly individuals was analyzed using 16S rRNA sequencing, the TMA levels in the feces of elderly were detected using headspace-gas chromatography (HS-GC), and four kinds of characterized TMA-producing intestinal bacteria in the elderly were quantified using real-time fluorescence quantitative polymerase chain reaction (qPCR). The results showed that Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and Verrucomicrobia are the dominant microorganisms of the intestinal flora in the Chinese elderly. And there were significant differences in the intestinal bacteria composition between healthy elderly individuals and those with CVD, accompanied by a notable difference in the TMA content. The richness and diversity of the intestinal flora in the elderly with CVD were higher than those in the healthy elderly. Correlation analysis indicated that certain significantly different intestinal flora were associated with the TMA levels. Our findings showed a significant difference in TMA-producing intestinal flora between healthy elderly individuals and those with CVD. The TMA levels were found to be positively and significantly correlated with Klebsiella pneumoniae, suggesting that this bacterium is closely linked to the production of TMA in the elderly gut. This may have implications for the development and progression of CVD in the elderly population.

#695 Modulation of probiotics on intestinal flora and related short-chain fatty acids in patients with peritoneal dialysis

Abstract Background and Aims Probiotics may play a role in inflammation, nutritional status, kidney function and quality of life. However, few studies were performed to study the effects of probiotics on metabolites of intestinal flora in patients. Method We investigated the effects of Lactobacillus paracasei N1115 on intestinal flora and related short-chain fatty acids in end stage kidney disease patients on peritoneal dialysis (PD) in a single-center, prospective, randomized, double-blind, placebo-controlled study (ChiCTR-TRC2016254). Fifty one patients on peritoneal dialysis underwent an intervention with the probiotic supplement (n = 36, PR group) or placebo (n = 15, PL group) for twelve weeks. In addition to collecting fecal samples for 16S rRNA gene high-throughput sequencing and short-chain fatty acids (SCFAs) analysis, gastrointestinal symptom was also assessed at baseline and after the intervention. Moreover, PR group was divided into gastrointestinal symptom remission group (n = 30, GR group) and gastrointestinal symptom non-remission group (n = 5, GNR group). Results Probiotic administration caused significant changes in the composition of gut microbiota, as indicated by increased abundance of beneficial bacteria (Firmicutes), decreased Bacteroidetes, and opportunistic pathogens (Fusobacterium, Bilophila) (p &amp;lt; 0.05). However, there was no significant difference in intestinal microbial diversity, SCFAs levels increased in PR group although the change was not statistically significant between the two groups (P &amp;gt; 0.05). In addition, probiotic administration could effectively reduce gastrointestinal symptoms, particularly in dyspepsia and constipation (p &amp;lt; 0.05). The contents of SCFAs was increased in GNR group (p &amp;lt; 0.05), and there was a significant correlation between these SCFAs and the differential bacterial genera with significant changes between the GR and GNR groups (p &amp;lt; 0.05). Conclusion Together, the results suggest that probiotic can promote the beneficial changes of intestinal flora in PD patients. Probiotic supplementation can improve the gastrointestinal symptoms of PD patients, possibly by affecting the composition of intestinal bacteria and their metabolites.

Fat and proteolysis due to methionine, tryptophan, and niacin deficiency leads to alterations in gut microbiota and immune modulation in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is one of the intractable diseases. Nutritional components associated with IBD have been identified, and it is known that excessive methionine intake exacerbates inflammation, and that tryptophan metabolism is involved in inflammation. Analysis of the gut microbiota has also progressed, where Lactobacillus regulate immune cells in the intestine and suppress inflammation. However, whether the methionine and tryptophan metabolic pathways affect the growth of intestinal Lactobacillus is unknown. Here we show how transient methionine, tryptophan, and niacin deficiency affects the host and gut microbiota in mouse models of colitis (induced by dextran sodium sulfate) fed a methionine-deficient diet (1K), tryptophan and niacin-deficient diet (2K), or methionine, tryptophan, and niacin-deficient diet (3K). These diets induced body weight decrease and 16S rRNA analysis of mouse feces revealed the alterations in the gut microbiota, leading to a dramatic increase in the proportion of Lactobacillus in mice. Intestinal RNA sequencing data confirmed that the expression of several serine proteases and fat-metabolizing enzymes were elevated in mice fed with methionine, tryptophan, and niacin (MTN) deficient diet. In addition, one-carbon metabolism and peroxisome proliferator-activated receptor (PPAR) pathway activation were also induced with MTN deficiency. Furthermore, changes in the expression of various immune-related cytokines were observed. These results indicate that methionine, tryptophan, and niacin metabolisms are important for the composition of intestinal bacteria and host immunity. Taken together, MTN deficiencies may serve as a Great Reset of gut microbiota and host gene expression to return to good health.

Gamma ray irradiation enhances defatted Hermetia illucens larvae meal as a dietary alternative to fishmeal for Acanthopagrus schlegelii juveniles

The current research investigated whether gamma (γ)-irradiation could improve the viability of defatted Hermetia illucens larvae (HIL) meal as a fishmeal alternative in black sea bream (Acanthopagrus schlegelii) diets. Three diets were formulated with equal protein (420 g/kg) and lipid (80 g/kg) contents. A diet containing 400 g/kg fishmeal was served as the control diet (C), and 50% of fishmeal in diet C was replaced by either defatted HIL meal or γ-irradiated defatted HIL meal to produce diet HR and diet HR10, respectively. Fish fed diet HR exhibited lower final body weight and weight gain compared to those fed diet C, while no statistically significant differences were found between fish fed diets C and HR10. Additionally, fish fed diet HR10 exhibited significantly lower feed intake, feed conversion rate, nitrogen waste, hepatic malondialdehyde content, relative usage of fishmeal and fish oil, fish-in to fish-out ratio, and economic conversion ratio, and meanwhile significantly higher nitrogen retention efficiency, hepatic total antioxidant capacity, economic profitability index and profitability, than those fed diet C. Fish fed different test diets showed statistically equal alpha diversity of intestinal microbiota, whereas the beta diversity of intestinal microbiota in group HR was far from groups C and HR10. Compared to fish fed diet C, the gut microbiota composition of fish fed diet HR showed significant alterations at both the phylum and genus levels. However, the altered composition of intestinal bacteria was partially restored in fish fed diet HR10. The above findings indicate that treating defatted HIL meal with γ-ray can reduce dietary fishmeal content for black sea bream to 200 g/kg without any adverse effects on growth, proximate composition and intestinal microbial diversity, and meanwhile ameliorates the feed utilization, hepatic antioxidant capacity, and intestinal microbiological composition of black sea bream. Furthermore, feeding γ-irradiated defatted HIL meal enhances the economic profitability, while reduces the waste output and reliance on fishery resource of black sea bream aquaculture.

Empagliflozin attenuates liver fibrosis in high-fat diet/streptozotocin-induced mice by modulating gut microbiota.

The effects of SGLT2 inhibitors on hepatic fibrosis in diabetes remain unclear. This study aimed to investigate the effects of empagliflozin on liver fibrosis in high-fat diet/streptozotocin-induced mice and the correlation with gut microbiota. After the application of empagliflozin for 6 weeks, we performed oral glucose tolerance and intraperitoneal insulin tolerance tests to assess glucose tolerance and insulin resistance, and stained liver sections to evaluate histochemical and hepatic pathological markers of liver fibrosis. Moreover, 16S rRNA amplicon sequencing was performed on stool samples to explore changes in the composition of intestinal bacteria. We finally analysed the correlation between gut microbiome and liver fibrosis scores or indicators of glucose metabolism. The results showed that empagliflozin intervention improved glucose metabolism and liver function with reduced liver fibrosis, which might be related to changes in intestinal microbiota. In addition, the abundance of intestinal probiotic Lactobacillus increased, while Ruminococcus and Adlercreutzia decreased after empagliflozin treatment, and correlation analysis showed that the changes in microbiota were positively correlated with liver fibrosis and glucose metabolism. Overall, considering the contribution of the gut microbiota in metabolism, empagliflozin might have improved the beneficial balance of intestinal bacteria composition. The present study provides evidence and indicates the involvement of the gut-liver axis by SGLT2 inhibitors in T2DM with liver fibrosis.

Polysaccharide from Panax japonicus C.A. Mey prevents non-alcoholic fatty liver disease development based on regulating liver metabolism and gut microbiota in mice

In this study, a new polysaccharide (PSPJ) with specific molecular weight and monosaccharide compositions was isolated and purified from the water extract of Panacis Japonici Rhizoma (PJR). 16S rRNA analysis and untargeted metabolomic analysis were used to assess PSPJ's efficacy in averting non-alcoholic fatty liver disease (NAFLD). This study indicated that PSPJ significantly reduced liver fat accumulation, the increase in blood lipids and ALT caused by HFD, indicating that PSPJ can prevent NAFLD. We demonstrated through cell experiments that PSPJ does not directly affect liver cells. The gut microbiota disorder and alterations in short-chain fatty acids (SCFAs) induced by the high-fat diet (HFD) were ameliorated by PSPJ, as evidenced by the analysis of 16S rRNA. In particular, supplementing PSPJ reduced the abundance of Turicibacter, Dubosiella, and Staphylococcus, and increased the abundance of Bacteroides, Blautia, and Lactobacillus. Untargeted metabolomic analysis shows that PSPJ improves liver metabolic disorders by regulating arachidonic acid metabolism, carbohydrate digestion and absorption, fatty acid biosynthesis, fatty acid metabolism and retinol metabolism. The findings of our investigation indicate that PSPJ has the potential to modulate liver metabolism through alterations in the composition of intestinal bacteria, hence preventing NAFLD.

Loss of Mptx2 alters bacteria composition and intestinal homeostasis potentially by impairing autophagy

A recent single-cell survey of the small-intestinal epithelium suggests that mucosal pentraxin 2 (Mptx2) is a new Paneth cell marker, but its function and involved mechanism in the Paneth cell are still unknown. Therefore, we create Mptx2 knockout (Mptx2−/−) mice to investigate its precise effects on intestinal homeostasis using models of lipopolysaccharide (LPS), methicillin-resistant Staphylococcus aureus (MRSA) peritoneal infection, and dextran sulfate sodium (DSS)–induced intestinal injury and inflammation. We here find that Mptx2 is selectively expressed in Paneth cells in the small intestines of mice. Mptx2−/− mice have increased susceptibility to intestinal inflammation and injured. Mptx2 deficiency reduces Paneth cell count and expression of antimicrobial factors, leading to altered intestinal bacteria composition. Loss of Mptx2 aggravates MRSA infection–induced damage in the intestine while decreasing autophagy in Paneth cells. Mptx2−/− mice are more vulnerable to LPS-induced intestinal possibly due to inhibition of the autophagy/endoplasmic reticulum (ER) stress pathway. Mptx2−/− mice are susceptible to DSS-induced colitis that could be ameliorated by treatment with gentamicin or vancomycin antibiotics. In conclusion, Mptx2 is essential to maintain intestinal homeostasis potentially via regulation of autophagy in Paneth cells.

Nutritional Interventions with Bacillus coagulans Improved Glucose Metabolism and Hyperinsulinemia in Mice with Acute Intermittent Porphyria.

Acute intermittent porphyria (AIP) is a metabolic disorder caused by mutations in the porphobilinogen deaminase (PBGD) gene, encoding the third enzyme of the heme synthesis pathway. Although AIP is characterized by low clinical penetrance (~1% of PBGD mutation carriers), patients with clinically stable disease report chronic symptoms and frequently show insulin resistance. This study aimed to evaluate the beneficial impact of nutritional interventions on correct carbohydrate dysfunctions in a mouse model of AIP that reproduces insulin resistance and altered glucose metabolism. The addition of spores of Bacillus coagulans in drinking water for 12 weeks modified the gut microbiome composition in AIP mice, ameliorated glucose tolerance and hyperinsulinemia, and stimulated fat disposal in adipose tissue. Lipid breakdown may be mediated by muscles burning energy and heat dissipation by brown adipose tissue, resulting in a loss of fatty tissue and improved lean/fat tissue ratio. Probiotic supplementation also improved muscle glucose uptake, as measured using Positron Emission Tomography (PET) analysis. In conclusion, these data provide a proof of concept that probiotics, as a dietary intervention in AIP, induce relevant changes in intestinal bacteria composition and improve glucose uptake and muscular energy utilization. Probiotics may offer a safe, efficient, and cost-effective option to manage people with insulin resistance associated with AIP.

Effects of fermented soybean meal substitution for fish meal on intestinal flora and intestinal health in pearl gentian grouper.

This study explored the role of replacing fish meal protein with fermented soybean meal (FSBM) protein on the growth performance and intestinal morphology, immunity, and microbiota of the pearl gentian grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂). Three isonitrogenous and isolipidic diets with increasing levels of FSBM (0%, 20% and 40%; referred to as FM, FSBM20 and FSBM40 diets, respectively) as a replacement for fish meal were selected for this study. The pearl gentian grouper were fed these diets for 10 weeks. The findings revealed that the growth of fish fed the FSBM diets (FSBM20 and FSBM40) were remarkably lower than the fish fed the FM diet. Pathological manifestations of intestinal inflammation, such as shortened intestinal mucosal folds and thickened lamina propria, were observed in the fish fed the FSBM diets. Moreover, the gene expression levels of IL1β, IL12, IL17, and TNFα were remarkably upregulated in fish fed the FSBM40 diet, in contrast to the gene expression levels of IL4, IL5, IL10, and TGFβ1, which were remarkably downregulated (p < 0.05). The FSBM diets significantly affected the stability of the fish gut microbiota. Photobacterium was the dominant phylum in all experimental groups, and the proportion of these bacteria gradually decreased with increasing FSBM substitution. The composition of intestinal flora at the genus level was not the same in the three experimental groups, with a richer composition of intestinal bacteria detected in the FSBM20 and FSBM40 groups (p < 0.05). The correlation between intestinal flora balance and immune gene expression revealed that only Photobacterium was negatively correlated with the above upregulated genes, while other bacteria were positively correlated with these pro-inflammatory factors (p < 0.05). Photobacterium was positively correlated with the above downregulated genes, while other bacteria were negatively correlated with these anti-inflammatory factors (p < 0.05). In conclusion, high levels of substitution of FSBM for fish meal causes intestinal inflammation in pearl gentian grouper. This is likely associated with changes to the intestinal flora. More attention should be paid to the negative role of dietary FSBM on intestinal flora.

FTZ polysaccharides ameliorate kidney injury in diabetic mice by regulating gut-kidney axis

BackgroundThe Fufang-zhenzhu-tiaozhi formula (FTZ), a traditional Chinese medicine (TCM) commonly used to treat metabolic diseases, potentially impacts the microbial ecosystem. Increasing evidence suggests that polysaccharides, bioactive components of TCMs, have great potential on kinds of diseases such as DKD by regulating intestinal flora. PurposeThis study aimed to investigate whether the polysaccharide components in FTZ (FTZPs) have beneficial effects in DKD mice via the gut-kidney axis. Study design and methodsThe DKD model in mice was established by streptozotocin combined with a high-fat diet (STZ/HFD). Losartan was used as a positive control, and FTZPs were administered at doses of 100 and 300 mg/kg daily. Renal histological changes were measured by H&E and Masson staining. Western blotting, quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to analyze the effects of FTZPs on renal inflammation and fibrosis, which were further confirmed using RNA sequencing. Immunofluorescence was used to analyze the effects of FTZPs on colonic barrier function in DKD mice. Faecal microbiota transplantation (FMT) was used to evaluate the contribution of intestinal flora. 16S rRNA sequencing was utilized to analyze the composition of intestinal bacteria, and UPLC-QTOF-MS-based untargeted metabolomics was used to identify the metabolite profiles. ResultsTreatment with FTZPs attenuated kidney injury, as indicated by the decreased urinary albumin/creatinine ratio and improved renal architecture. FTZPs downregulated the expression of renal genes associated with inflammation, fibrosis, and systematically blunted related pathways. FTZPs also restored the colonic mucosal barrier and increased the expression of tight junction proteins (E-cadherin). The FMT experiment confirmed the substantial contribution of the FTZPs-reshaped microbiota to relieving DKD symptoms. Moreover, FTZPs elevated the content of short-chain fatty acids (propionic acid and butanoic acid) and increased the level of the SCFAs transporter Slc22a19. Intestinal flora disorders caused by diabetes, including the growth of the genera Weissella, Enterococcus and Akkermansia, were inhibited by FTZPs treatment. Spearman's analysis revealed that these bacteria were positively correlated with indicators of renal damage. ConclusionThese results show that oral administration of FTZPs, by altering SCFAs levels and the gut microbiome, is a therapeutic strategy for the treatment of DKD.

The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation.

Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes.In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes.

High fiber diet attenuate the inflammation and adverse remodeling of myocardial infarction via modulation of gut microbiota and metabolites.

High intake of dietary fiber is associated with lower incidence of cardiovascular diseases. Dietary fiber, functions as a prebiotic, has a significant impact on intestinal bacteria composition and diversity. The intestinal flora and metabolites generated by fermentation of dietary fiber not only affect the health of intestine but also play a role in many extra-intestinal diseases, such as obesity, diabetes and atherosclerosis. However, the role and the mechanism by which a high fiber diet contributes to the development of myocardial infarction is still unclear. Here we used an in vivo mouse model to investigate whether dietary fiber intake could protect against myocardial infarction. Our study demonstrated high fiber diet significantly improved cardiac function, reduced infarct size and prevented adverse remodeling following myocardial infarction. The protective effects of high fiber diet had a strong relation with its attenuation of inflammation. Moreover, we observed that high fiber diet could modulate the composition of intestinal flora and differentially impacted metabolites production, including the biosynthesis of bile acids and linoleic acid metabolism. Overall, the findings of this study provided mechanistic insights into the curative effect of dietary fiber on myocardial infarction with a specific emphasis on the potential role of microbiota-metabolism-immunity interactions.

Gut microbiota mediates the pharmacokinetics of Zhi-zi-chi decoction for the personalized treatment of depression

Ethnopharmacological relevanceZhi-zi-chi decoction (ZZCD), from “Treatise on Febrile Diseases”, is a typical traditional Chinese medicine herb pair, which consists of Gardeniae Fructus (GF) and Semen Sojae Praeparatu (SSP). In clinical research, ZZCD was widely used to fight depression, remove annoyance. Many studies have reported that gut microbiota is critical target for the influence of depress through gut-brain axis, and our previously studies have found that ZZCD exhibiting antidepressant effect was through the gut-brain axis. However, the specific mechanism by which gut microbiota mediates the pharmacokinetics parameters of active compounds from ZZCD during the process of depression treatment has not yet been studied. Aim of the studyTo explore the differences in pharmacokinetics characters of bioactive iridoids from ZZCD and study the changes of gut microbiota at different stages of depression with the personalized medicine of ZZCD. Materials and methodsA new strategy exploring the relationship among disease phenotypes (D), intestinal microbiota (I), enzymes (E) and traits of metabolism (T) named as “DIET” was established. Firstly, a fast, selective and sensitive ultra-performance liquid chromatography coupled with tandem mass spectrometer (UPLC-MS/MS) was established and validated to quality the main bioactive compounds from ZZCD and compare the pharmacokinetics and bioavailability of different iridoids prototypes and metabolites from ZZCD between normal and chronic unpredictable mild stress rats. Subsequently, the activity of corresponding metabolic enzymes of anti-depressive compounds, β-glucosidases and sulfotransferases, were analyzed by ρ-nitrophenyl-β -D-glucopyranoside and sulfotransferases ELISA kits, respectively. Finally, 16S rRNA gene sequencing was adopt to analyze intestinal bacteria composition for the treatment of depression by ZZCD. ResultsThe antidepressant effect of ZZCD was promoted due to the increased exposures and reduced eliminations of anti-depressive compounds, especially geniposide and genipin 1-gentiobioside, under the depression state. With the ZZCD treatment, the depression was improved, but the exposures of anti-depressive compounds from ZZCD gradually decreased. Meanwhile, there were the corresponding decreased trends on the activity of β-glucosidases and sulfotransferases. With the consumption of ZZDC and the improvement of depression, the exposures of anti-depressive iridoid glycosides decreased and the activity of metabolism enzymes restored. Meanwhile, the dysbiosis of pathogenic bacteria (Bacteroidota) induced by depression was ameliorated and the probiotics (Firmicutes) at the phylum and genus level raised, the two phyla are closely related to the production of β-glucosidase and sulfotransferases. ConclusionsIt is the first proposed that ZZCD could personalized to treat depression at different stages targeting gut microbiota and gut microbiome could emerged as a potential diagnostic and therapeutic biomarker in depression.

The Crosstalk between the Gut Microbiota Composition and the Clinical Course of Allergic Rhinitis: The Use of Probiotics, Prebiotics and Bacterial Lysates in the Treatment of Allergic Rhinitis.

Although massive progress in discovering allergic rhinitis (AR) aetiology has been made in recent years, its prevalence is still rising and it significantly impacts patients’ lives. That is why further and non-conventional research elucidating the role of new factors in AR pathogenesis is needed, facilitating discoveries of new treatment approaches. One of these factors is the gut microbiota, with its specific roles in health and disease. This review presents the process of gut microbiota development, especially in early life, focusing on its impact on the immune system. It emphasizes the link between the gut microbiota composition and immune changes involved in AR development. Specifically, it elucidates the significant link between bacteria colonizing the gut and the Th1/Th2 imbalance. Probiotics, prebiotics and bacterial lysates, which are medications that restore the composition of intestinal bacteria and indirectly affect the clinical course of AR, are also discussed.

Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn's disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets.

ObjectivesA number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.MethodsMetagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi’omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.ResultsCompared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.ConclusionsIn conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.

Antimicrobial treatment improves tryptophan metabolism and mood of patients with small intestinal bacterial overgrowth

BackgroundOptimal composition of intestinal bacteria is an essential condition for good health. Excessive growth of these bacteria can cause various ailments. The aim of this study was to assess the mental state and gastrointestinal complaints of patients with small intestinal bacterial overgrowth (SIBO) in relation to tryptophan metabolism and rifaximin treatment.Methods120 subjects, aged 23–61 years, were enrolled in the study, and divided into 3 groups, 40 individuals each: healthy subjects (Controls), patients with SIBO and chronic diarrhea (SIBO-D), and with chronic constipation (SIBO-C). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The mental state of patients was assessed using the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D). L-tryptophan (TRP) and its metabolites: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), xanthurenic acid (XA) and quinolinic acid (QA) were measured in urine by liquid-chromatography-tandem mass spectrometry and related to creatinine level. Patients with SIBO were recommended to take rifaximin for 10 days at daily dose 1200 mg, and this cycle was repeated in subsequent two months.ResultsMild and moderate anxiety, as well as mild depression were diagnosed in all SIBO patients. Changes in TRP metabolism were also observed in these patients. Specifically, an increase in the activity of the serotonin pathway of TRP metabolism in the group SIBO-D was observed. The SIBO-C patients showed an increase in the concentration of KYN, XA and QA. 5-HIAA/TRP and KYN/TRP ratios significantly decreased in group SIBO-D, and KYN and QA levels decreased in group SIBO-C after treatment with rifaximin. The levels of anxiety and depression decreased in both groups.ConclusionRifaximin treatment of SIBO patients ameliorated their mood disorders and gastrointestinal aliments underlined by changes in tryptophan metabolism.Trial registration Retrospectively registered (if applicable).

Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. Microbial infection is considered a crucial inducer of RA. Alterations in the composition of intestinal bacteria in individuals with preclinical and established RA suggest a vital role of the gut microbiota in immune dysfunction characteristic of RA. However, the mechanisms by which gut dysbiosis contributes to RA are not fully understood. Furthermore, multiple therapies commonly used to treat RA may alter gut microbiota diversity, suggesting that modulating the gut microbiota may help prevent or treat RA. Hence, a better understanding of the changes in the gut microbiota that accompany RA should aid the development of novel therapeutic approaches. This mini-review discusses the impact of gut dysbiosis in the pathogenesis of RA, the selection of gut microbiota-related biomarkers for diagnosing RA, and provides examples of cross-modulation between the gut microbiota and some drugs commonly used to treat RA. Some suggestions and outlooks are also raised, which may help guide future research efforts.