Fecal Gut Microbiota Research Articles

Fecal microbiota transplantation as an effective way in treating methylmercury-poisoned rats

Methylmercury (MeHg) can cause devastating neurotoxicity in animals and human beings. Gut microbiota dysbiosis has been found in MeHg-poisoned animals. Fecal microbiota transplantation (FMT) has been shown to improve clinical outcomes in a variety of diseases such as epilepsy, amyotrophic lateral sclerosis (ALS) and autism. The aim of this study was to investigate the effects of FMT on MeHg-poisoned rats. FMT treatment was applied to MeHg-poisoned rats for 14 days. The neurobehavior, weight changes, dopamine (DA), the total Hg and MeHg level were evaluated. Besides, the gut microbiota and metabolites change in feces were also checked. It was found that FMT helped weight gain, alleviated the neurological disorders, enhanced fecal mercury excretion and MeHg demethylation, reconstructed gut microbiome and promoted the production of gut-brain axis related-metabolites in MeHg-poisoned rats. This study elaborates on the therapeutic efficacy of FMT in treating of MeHg-poisoned rats, which sheds lights on the treatment of neurological diseases like Minamata Disease and even Parkinson's Disease.

Changes in amino acid concentrations and the gut microbiota composition are implicated in the mucosal healing of ulcerative colitis and can be used as noninvasive diagnostic biomarkers

BackgroundMucosal healing is the therapeutic target for ulcerative colitis (UC). While amino acids (AAs) and the gut microbiota are known to be involved in the pathogenesis of UC, their specific roles in mucosal healing have not been fully defined.ObjectivesTo longitudinally assess the changes in AA concentrations and the gut microbiota composition in the context of mucosal healing in UC patients, with the aim of identifying new biomarkers with predictive value for mucosal healing in UC patients and providing a new theoretical basis for dietary therapy.MethodsA total of 15 UC patients with infliximab-induced mucosal healing were enrolled. Serum and fecal AA concentrations before and after mucosal healing were determined via targeted metabolomics. A receiver operating characteristic (ROC) curve was plotted to evaluate the value of different AAs in predicting mucosal healing in UC patients. The changes in the composition of the fecal gut microbiota were analyzed via metagenomics, and bioinformatics was used to analyze the functional genes and metabolic pathways associated with different bacterial species. Spearman correlation analyses of fecal AAs with significantly different concentrations and the differentially abundant bacterial species before and after mucosal healing were performed.Results1. The fecal concentrations of alanine, aspartic acid, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine were significantly decreased after mucosal healing. The serum concentrations of alanine, cysteine and valine significantly increased, whereas that of aspartic acid significantly decreased. Glutamic acid, leucine, lysine, methionine and threonine could accurately predict mucosal healing in UC patients, and the area under the curve (AUC) was > 0.9. After combining the 5 amino acids, the AUC reached 0.96. 2. There were significant differences in the gut microbiota composition before and after mucosal healing in UC, characterized by an increase in the abundance of beneficial microbiota (Faecalibacterium prausnitzii and Bacteroides fragilis) and a decrease in the abundance of harmful microbiota (Enterococcus faecalis). LEfSe analysis identified 57 species that could predict mucosal healing, and the AUC was 0.7846. 3. Amino acid metabolic pathways were enriched in samples after mucosal healing, was associated with the abundance of multiple species, such as Faecalibacterium prausnitzi, Bacteroides fragilis, Bacteroides vulgatus and Alistipes putredinis. 4. The fecal concentrations of several AAs were negatively correlated with the abundance of a variety of beneficial strains, such as Bacteroides fragilis, uncultured Clostridium sp., Firmicutes bacterium CAG:103, Adlercreutzia equolifaciens, Coprococcus comes and positively correlated with the abundance of several harmful strains, such as Citrobacter freundii, Enterococcus faecalis, Klebsiella aerogenes, Salmonella enterica.ConclusionAltered concentrations of amino acids and their associations with the gut microbiota are implicated in the mucosal healing of UC patients and can serve as noninvasive diagnostic biomarkers.

Fecal microbiota transplantation and gut microbiota reconstruction in patients with refractory diarrhea

Fecal microbiota transplantation and gut microbiota reconstruction in patients with refractory diarrhea

Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8+ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8+ T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8+ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

Unveiling the gut microbiota blueprint of schizophrenia: a multilevel omics approach.

Schizophrenia is a persistent incurable mental disorder and is characterized by the manifestation of negative emotions and behaviors with anxiety and depression, fear and insecurity, self-harm and social withdrawal. The intricate molecular mechanisms underlying this phenomenon remain largely elusive. Accumulating evidence points towards the gut microbiota exerting an influence on brain function via the gut-brain axis, potentially contributing to the development of schizophrenia. Therefore, the objective of this study is to delineate the gut microbial composition and metabolic profile of fecal samples from individuals with schizophrenia. Liquid chromatography-mass spectrometry (LC-MS) and 16S ribosomal RNA (16S rRNA) gene sequencing were employed to analyze fecal metabolites and gut microbiota profiles in a cohort of 29 patients diagnosed with schizophrenia and 30 normal controls. The microbial composition of fecal samples was determined through the 16S rRNA gene sequencing, and microbial α-diversity and β-diversity indices were calculated. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to analyze the distribution of samples. The metabolites and gut microbiota exhibiting differential expression were identified through the application of biological variance criteria. Co-occurrence analysis of bacteria and metabolites was conducted using the spearman's rank correlation coefficient and visualized in a circular layout with the Cytoscape software. The findings of the study indicated a lack of substantial evidence supporting significant disparities in α-diversity and β-diversity between individuals with schizophrenia and normal controls. In terms of metabolomics, a discernible pattern in sample distribution between the two groups was observed. Our analysis has revealed 30 bacterial species and 45 fecal metabolites that exhibited notable differences in abundance between individuals diagnosed with schizophrenia and normal controls. These alterations in multilevel omics have led to the development of a co-expression network associated with schizophrenia. The perturbed microbial genes and fecal metabolites consistently demonstrated associations with amino acid and lipid metabolism, which play essential roles in regulating the central nervous system. Our results offered profound insights into the impact of imbalanced gut microbiota and metabolism on brain function in individuals with schizophrenia.

Nutraceutical Capsules LL1 and Silymarin Supplementation Act on Mood and Sleep Quality Perception by Microbiota-Gut-Brain Axis: A Pilot Clinical Study.

Stress, unhealthy lifestyle, and sleep disturbance worsen cognitive function in mood disorders, prompting a rise in the development of integrative health approaches. The recent investigations in the gut-brain axis field highlight the strong interplay among microbiota, inflammation, and mental health. Thus, this study aimed to investigate a new nutraceutical formulation comprising prebiotics, minerals, and silymarin's impact on microbiota, inflammation, mood, and sleep quality. The study evaluated the LL1 + silymarin capsule supplementation over 180 days in overweight adults. We analyzed the fecal gut microbiota using partial 16S rRNA sequences, measured cytokine expression via CBA, collected anthropometric data, quality of life, and sleep questionnaire responses, and obtained plasma samples for metabolic and hormonal analysis at baseline (T0) and 180 days (T180) post-supplementation. Our findings revealed significant reshaping in gut microbiota composition at the phylum, genus, and species levels, especially in the butyrate-producer bacteria post-supplementation. These changes in gut microbiota were linked to enhancements in sleep quality, mood perception, cytokine expression, and anthropometric measures which microbiota-derived short-chain fatty acids might enhance. The supplementation tested in this study seems to be able to improve microbiota composition, reflecting anthropometrics and inflammation, as well as sleep quality and mood improvement.

Gut microbiota patterns associated with duration of diarrhea in children under five years of age in Ethiopia

Diarrhea claims >500,000 lives annually among children under five years of age in low- and middle-income countries. Mortality due to acute diarrhea (<7 days’ duration) is decreasing, but prolonged (7-13 days) and persistent (≥14 days of duration) diarrhea remains a massive challenge. Here, we use a case-control study to decipher if fecal gut microbiota compositional differences between Ethiopian children with acute (n=554) or prolonged/persistent (n=95) diarrhea and frequency-matched non-diarrheal controls (n=663) are linked to diarrheal etiology. We show that diarrhea cases are associated with lower bacterial diversity and enriched in Escherichia spp., Campylobacter spp., and Streptococcus spp. Further, diarrhea cases are depleted in gut commensals such as Prevotella copri, Faecalibacterium prausnitzii, and Dialister succinatiphilus, with depletion being most pronounced in prolonged/persistent cases, suggesting that prolonged duration of diarrhea is accompanied by depletion of gut commensals and that re-establishing these via e.g., microbiota-directed food supplements offer a potential treatment strategy.

Effect of oral metformin on gut microbiota characteristics and metabolite fractions in normal-weight type 2 diabetic mellitus patients.

To analyze the effect of oral metformin on changes in gut microbiota characteristics and metabolite composition in normal weight type 2 diabetic patients. T2DM patients in the cross-sectional study were given metformin for 12 weeks. Patients with unmedicated T2DM were used as a control group to observe the metrics of T2DM patients treated with metformin regimen. 16S rDNA high-throughput gene sequencing of fecal gut microbiota of the study subjects was performed by llumina NovaSeq6000 platform. Targeted macro-metabolomics was performed on 14 cases of each of the gut microbiota metabolites of the study subjects using UPLC-MS/MS technology. Correlations between the characteristics of the gut microbiota and its metabolites, basic human parameters, glycolipid metabolism indicators, and inflammatory factors were analyzed using spearman analysis. Glycolipid metabolism indexes and inflammatory factors were higher in normal-weight T2DM patients than in the healthy population (P<0.05), but body weight, BMI, waist circumference, and inflammatory factor concentrations were lower in normal-weight T2DM patients than in obese T2DM patients (P<0.05). Treatment with metformin in T2DM patients improved glycolipid metabolism, but the recovery of glycolipid metabolism was more pronounced in obese T2DM patients. None of the differences in α-diversity indexes were statistically significant (P>0.05), and the differences in β-diversity were statistically significant (P <0.05). Community diversity and species richness recovered after metformin intervention compared to before, and were closer to the healthy population. We found that Anaerostipes/Xylose/Ribulose/Xylulose may play an important role in the treatment of normal-weight T2DM with metformin by improving glycemic lipids and reducing inflammation. And Metformin may play a role in obese T2DM through Romboutsia, medium-chain fatty acids (octanoic acid, decanoic acid, and dodecanoic acid). Gut microbial dysbiosis and metabolic disorders were closely related to glucose-lipid metabolism and systemic inflammatory response in normal-weight T2DM patients. Metformin treatment improved glucose metabolism levels, systemic inflammation levels in T2DM patients, closer to the state of healthy population. This effect may be mediated by influencing the gut microbiota and microbial host co-metabolites, mainly associated with Anaerostipes and xylose/Ribulose/Xylulose. Metformin may exert its effects through different pathways in normal-weight versus obese T2DM patients.

Exploring the diagnostic potential of immunoglobulin A-microbiota interplay in liver cirrhosis and spontaneous bacterial peritonitis.

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.

Antidepressant effect of carvedilol on streptozotocin-induced diabetic peripheral neuropathy mice by altering gut microbiota

RationaleAlthough diabetic peripheral neuropathic pain (DPNP) and depression have been recognized for many years, their co-morbidity relationship and effective treatment choices remain uncertain. ObjectivesTo evaluate the antidepressant effect of carvedilol on streptozotocin-induced DPNP mice, and the relationship with gut microbiota. MethodsThe hyperalgesia and depressive behaviors of mice with comorbidity of DPNP and depression were confirmed by pain threshold of the mechanical sensitivity test (MST), immobility time of the tail suspension test (TST) and the forced swimming test (FST). The anti-depressive effect and fecal gut microbiota composition were studied in DPNP mice treated with carvedilol (10 mg/kg/day), and the relationships between them were analyzed by Spearman's correlation. ResultsDepression was successfully induced in DPNP mice. Carvedilol can reverse the decreased mechanical pain threshold and relieve the depressive behaviors of DPNP mice, while increasing the abundance of Prevotella, Ruminococcus, Helicobacter and Desulfovibrio, and decreasing the abundance of Akkermansia and Allobaculum. ConclusionsCarvedilol can alleviate the mechanical hyperalgesia and alter gut microbiota to ameliorate the depression-like behaviors which induced by DPNP.

Impact of a legumes diet on the human gut microbiome articulated with fecal and plasma metabolomes: A pilot study

Background & AimsLegumes intake is known to be associated with several health benefits the origins of which is still a matter of debate. This paper addresses a pilot small cohort to probe for metabolic aspects of the interplay between legumes intake, human metabolism and gut microbiota. MethodsUntargeted nuclear magnetic resonance (NMR) metabolomics of blood plasma and fecal extracts was carried out, in tandem with qPCR analysis of feces, to assess the impact of an 8-week pilot legumes diet intervention on the fecal and plasma metabolomes and gut microbiota of 19 subjects. ResultsWhile the high inter-individual variability hindered the detection of statistically significant changes in the gut microbiome, increased fecal glucose and decreased threonine levels were noted. Correlation analysis between the microbiome and fecal metabolome lead to putative hypotheses regarding the metabolic activities of prevalent bacteria groups (Clostridium leptum subgroup, Roseburia spp., and F. prausnitzii). These included elevated fecal glucose as a preferential energy source, the involvement of valerate/isovalerate and reduced protein degradation in gut microbiota. Plasma metabolomics advanced mannose and betaine as potential markers of legume intake and unveiled a decrease in formate and ketone bodies, the latter suggesting improved energy utilization through legume carbohydrates. Amino acid metabolism was also apparently affected, as suggested by lowered urea, histidine and threonine levels. ConclusionsDespite the high inter-individual gut microbiome variability characterizing the small cohort addressed, combination of microbiological measurements and untargeted metabolomics unveiled several metabolic effects putatively related to legumes intake. If confirmed in larger cohorts, our findings will support the inclusion of legumes in diets and contribute valuable new insight into the origins of associated health benefits.

The main factors that improve gut microbiota composition

The aim is to observe and compare the main factors that can improve gut microbiota composition. Materials and methods. The literature study research was performed in PubMed and Google Scholar electronic databases. We assessed more than 300 studies, data from 65 of which were included in this review. They are presented in three tables: nonpharmacological influence on gut microbiota composition, drugs impact on gut microbiota, and medicines prescribed for gut microbiota correction. Results. On the one hand, non-pharmacological methods of gut microbiota improvement are the safest and the most traditional: healthy diet and physical activity, good sleep, avoiding stress and bad habits, but they are the most difficult for patients’ fulfillment and doctors’ observation. All listed are the components of a healthy way of life and should be followed by everybody. The most prescribed drugs have a significant influence on gut microbiota composition, so physicians should consider their effects in prescriptions. They are antibiotics, steroids and non-steroids, proton pump inhibitors, laxatives, antidepressants, etc. On the other hand, despite the diversity of available medicines (prebiotics, probiotics, paraprobiotics, postbiotics, synbiotics, and antibiotics) that can be used for gut microbiota improvement, all of them are under investigation and need further evaluation. The trendiest medicines for today are paraprobiotics and postbiotics. Paraprobiotics are represented by heat / ultraviolet / sonication Lactobacillus spp., Bifidobacterium spp., and Saccharomyces strains. Postbiotics are performed by short-chain fatty acids, secreted biosurfactants, secreted proteins, organic acids, amino acids, bacteriocins, vitamins, and peptides. Most of the data on their pharmacodynamics is based on animal studies or experimental research, so they need further investigations. Fecal gut microbiota transplantation is also an up-to-date method for multiple disease correction but is approved only for the treatment of recurrent and refractory infections caused by Clostridium difficile. Conclusions. Gut microbiota composition improvement methods are an up-to-date topic for practical medicine because gut microbiota changes are closely linked with host health status. Gut microbiota violations lead to metabolic, cardiovascular, neurological, inflammatory disorders, etc. Nowadays the healthy way of life is the best gut microbiota composition improvement method, but prebiotics, probiotics, paraprobiotics, postbiotics, synbiotics, antibiotics supplementation, and fecal microbiota transplantation also take place and have their indisputable advantages in special cases. Unfortunately, most pharmacological methods of gut microbiota modulation have a weak evidence base. Therefore, this question needs further research in appropriate patient groups with long-term monitoring.

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

BackgroundProstate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa.MethodsA mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development.ResultsAfter treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2.ConclusionsICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.

Nutraceutical blends predict enhanced health via microbiota reshaping improving cytokines and life quality: a Brazilian double-blind randomized trial

Nutraceutical interventions supporting microbiota and eliciting clinical improvements in metabolic diseases have grown significantly. Chronic stress, gut dysbiosis, and metainflammation have emerged as key factors intertwined with sleep disorders, consequently exacerbating the decline in quality of life. This study aimed to assess the effects of two nutraceutical formulations containing prebiotics (fructooligosaccharides (FOS), galactooligosaccharides (GOS), yeast β-glucans), minerals (Mg, Se, Zn), and the herbal medicine Silybum marianum L. Gaertn., Asteraceae (Milk thistle or Silymarin). These formulations, namely NSupple (without silymarin) and NSupple_Silybum (with silymarin) were tested over 180 days in overweight/obese volunteers from Brazil's southeastern region. We accessed fecal gut microbiota by partial 16S rRNA sequences; cytokines expression by CBA; anthropometrics, quality of life and sleep, as well as metabolic and hormonal parameters, at baseline (T0) and 180 days (T180) post-supplementation. Results demonstrated gut microbiota reshaping at phyla, genera, and species level post-supplementation. The Bacteroidetes phylum, Bacteroides, and Prevotella genera were positively modulated especially in the NSupple_Silybum group. Gut microbiota modulation was associated with improved sleep patterns, quality-of-life perception, cytokines expression, and anthropometric parameters post-supplementation. Our findings suggest that the nutraceutical blends positively enhance cardiometabolic and inflammatory markers. Particularly, NSupple_Silybum modulated microbiota composition, underscoring its potential significance in ameliorating metabolic dysregulation. Clinical trial registry number: NCT04810572. 23/03/2021.

High-fat diet induces sarcopenic obesity in natural aging rats through the gut–trimethylamine N-oxide–muscle axis

IntroductionThe lack of suitable animal models for sarcopenic obesity (SO) limits in-depth research into the disease. Emerging studies have demonstrated that gut dysbiosis is involved in the development of SO. As the importance of microbial metabolites is starting to unveil, it is necessary to comprehend the specific metabolites associated with gut microbiota and SO. ObjectivesWe aimed to investigate whether high-fat diet (HFD) causes SO in natural aging animal models and specific microbial metabolites that are involved in linking HFD and SO. MethodsYoung rats received HFD or control diet for 80 weeks, and obesity-related metabolic disorders and sarcopenia were measured. 16S rRNA sequencing and non-targeted and targeted metabolomics methods were used to detect fecal gut microbiota and serum metabolites. Gut barrier function was evaluated by intestinal barrier integrity and intestinal permeability. Trimethylamine N-oxide (TMAO) treatment was further conducted for verification. ResultsHFD resulted in body weight gain, dyslipidemia, impaired glucose tolerance, insulin resistance, and systemic inflammation in natural aging rats. HFD also caused decreases in muscle mass, strength, function, and fiber cross-sectional area and increase in muscle fatty infiltration in natural aging rats. 16S rRNA sequencing and nontargeted and targeted metabolomics analysis indicated that HFD contributed to gut dysbiosis, mainly characterized by increases in deleterious bacteria and TMAO. HFD destroyed intestinal barrier integrity and increased intestinal permeability, as evaluated by reducing levels of colonic mucin-2, tight junction proteins, goblet cells and elevating serum level of fluorescein isothiocyanate-dextran 4. Correlation analysis showed a positive association between TMAO and SO. In addition, TMAO treatment aggravated the development of SO in HFD-fed aged rats through regulating the ROS-AKT/mTOR signaling pathway. ConclusionHFD leads to SO in natural aging rats, partially through the gut–microbiota–TMAO–muscle axis.

A metagenomic approach to unveil the association between fecal gut microbiota and short-chain fatty acids in diarrhea caused by diarrheagenic Escherichia coli in children.

Diarrheagenic Escherichia coli (DEC) is the main cause of diarrhea in children under five years old. The virulence of DEC is tightly regulated by environmental signals influenced by the gut microbiota and its metabolites. Short-chain fatty acids (SCFAs) are the main metabolic product of anaerobic fermentation in the gut, but their role in DEC diarrhea has not yet been established. In this study, we determine the levels of acetate, propionate, and butyrate in stool samples from children with diarrhea caused by DEC, and we identify bacteria from the fecal gut microbiota associated with the production of SCFAs. The microbiota and SCFAs levels in stool samples obtained from 40 children with diarrhea and 43 healthy children were determined by 16S rRNA gene sequencing and HPLC, respectively. Additionally, shotgun metagenomics was used to identify metagenome-assembled genomes (MAGs) in a subgroup of samples. The results showed significantly higher levels of all SCFAs tested in diarrheal samples than in healthy controls. The abundance of Streptococcus sp., Limosilactobacillus, Blautia, Escherichia, Bacteroides, Megamonas, and Roseburia was higher in the DEC group than in healthy individuals. Functional analysis of bacteria and their main metabolic pathways made it possible to identify species MAGs that could be responsible for the detected SCFAs levels in DEC-positive diarrhea. In conclusion, based on our results and published data, we suggest that SCFAs may be important in the crosstalk between the microbiota and DEC pathogens in the gut.

A multi-omics approach to investigate characteristics of gut microbiota and metabolites in hypertension and diabetic nephropathy SPF rat models.

Imbalance in intestinal microbiota caused by microbial species and proportions or metabolites derived from microbes are associated with hypertension, as well as diabetic nephropathy. However, the involvement of the intestinal microbiota and metabolites in hypertension and diabetic nephropathy comorbidities (HDN) remains to be elucidated. We investigated the effects of intestinal microbiota on HDN in a rat model and determined the abundance of the intestinal microbiota using 16S rRNA sequencing. Changes in fecal and serum metabolites were analyzed using ultra-high-performance liquid chromatography-mass spectrometry. The results showed abundance of Proteobacteria and Verrucomicrobia was substantially higher, whereas that of Bacteroidetes was significant lower in the HDN group than in the sham group. Akkermansia, Bacteroides, Blautia, Turicibacter, Lactobacillus, Romboutsia, and Fusicatenibacter were the most abundant, and Prevotella, Lachnospiraceae_NK4A136_group, and Prevotella_9 were the least abundant in the HDN group. Further analysis with bile acid metabolites in serum showed that Blautia was negatively correlated with taurochenodeoxycholic acid, taurocholic acid, positively correlated with cholic acid and glycocholic acid in serum. These findings suggest that the gut microbiota and metabolites in feces and serum substantially differed between the HDN and sham groups. The F/B ratio was higher in the HDN group than in the sham group. Blautia is potentially associated with HDN that correlated with differentially expressed bile acid metabolites, which might regulate the pathogenesis of HDN via the microorganism-gut-metabolite axis.

Gut Microbiota-Derived Tryptophan Metabolites Alleviate Allergic Asthma Inflammation in Ovalbumin-Induced Mice.

Asthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p < 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance of Anaeroplasma, Akkermansia, and Ruminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.

Effects of complex polysaccharides by Ficus carica Linn. polysaccharide and peach gum on the development and metabolites of human gut microbiota

Both Ficus carica Linn. polysaccharide and peach gum had beneficial effects on human gut microbiota. However, their complex polysaccharides have never been studied during the fecal fermentation in vitro. Therefore, this study investigated the effects of Ficus carica Linn. polysaccharide (FCPS), peach gum polysaccharide (PGPS) and their complex polysaccharides on fecal fermentation characteristics and gut microbiota composition in vitro. The changes of pH, gas production and short-chain fatty acids (SCFAs) in the metabolites were measured at 0, 6, 9, 12 and 24 h under anaerobic conditions. The changes of gut microbiota were measured at 24 h. The results of metabolite determination showed that FCPS and FCPG2_1 had strong acid production, pH reduction and gas production ability, while the PGPS had poor effect. The results of gut microbiota analysis showed that Firmicutes, Bacteroidetes and Proteobacteria were the dominant phyla in the fermentation process, and the ratio of Firmicutes to Bacteroidetes was the lowest in the FCPG1_1. At the genus level, the promoting effects of these five polysaccharides on different genera were different. FCPS notably augmented the proliferation of Bacteroides and Phascolarctobacterium. Similarly, FCPG1_1 significantly enhanced the growth of Faecalibacterium and Paraprevotella. Furthermore, FCPG2_1 was responsible for an upsurge in the proliferation of the Lachnospiraceae_NK4A136_group, whereas PGPS proved excellent in stimulating Roseburia's growth. In summary, complex polysaccharides and FCPS were better, and they had potential anti-obesity effects. This study had practical significance for the development of functional food and dietary intervention.

Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short-Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD).

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short-chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography-mass spectrometry and 16S rRNA gene sequencing. Compared with NC, fecal SCFA levels (propionic, acetic, and butyric acid) were lower in iRBD, MSA, and PD. Combinations of these SCFAs could differentiate NC from iRBD (AUC 0.809), MSA (AUC 0.794), and PD (AUC 0.701). Decreased fecal SCFAs were associated with the common reducing SCFA-producing gut microbiota in iRBD, MSA, and PD. iRBD shares similar fecal SCFA alterations with MSA and PD, and the combination of these SCFAs might be a potential synucleinopathies-related biomarker. © 2024 International Parkinson and Movement Disorder Society.