Disturbance Of Intestinal Microbiota Research Articles

Preliminary study on the potential impact of probiotic combination therapy on Helicobacter pylori infection in children using 16S gene sequencing and untargeted metabolomics approach

ObjectiveThe purpose of this study was to explore the potential mechanism of Helicobacter pylori (Hp) eradication by probiotic therapy through 16S rRNA gene sequencing technology and untargeted metabolomics.MethodsTwenty four Hp-infected children were recruited from the Shanxi Bethune Hospital, and 24 healthy children were recruited as a blank control group. Group A: fecal samples from 24 healthy children. Group B: fecal samples of 24 children with Hp infection. Group B1 (n = 15): fecal samples of group B treated with probiotic therapy for 2 weeks. Group B2 (n = 19): fecal samples of group B treated with probiotic therapy for 4 weeks. The above fecal samples were analyzed by 16S rRNA gene sequencing technology and untargeted metabolomics.ResultsThere was no significant difference in alpha diversity and beta diversity among the four groups, but many bacteria with statistical difference were found in each group at the bacterial genus level and phylum level. LEfSe results showed that in group B, Porphyromonadaceae, Shigella and other microorganisms related to intestinal microecological dysbiosis were enriched. And in group B2, abundant characteristic microorganisms were found, namely Bacillales and Prevotella. KEGG metabolic pathway enrichment analysis showed that groups B1 and B2 were involved in 10 metabolic pathways potentially related to probiotic treatment: purine metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartic acid and glutamate metabolism, glyoxylic acid and dicarboxylic acid metabolism, unsaturated fatty acid biosynthesis, fatty acid extension, fatty acid degradation, pyrimidine metabolism, fatty acid biosynthesis.ConclusionProbiotic therapy can inhibit Hp to some extent and can relieve gastrointestinal symptoms, making it a preferred therapy for children with Hp infection and functional abdominal pain. Hp infection can reduce the diversity of intestinal microbes, resulting in the disturbance of intestinal microbiota and changes in the relative abundance of microbiota in children, while probiotic therapy can restore the diversity of intestinal microbes and intestinal microecological balance.

Intestinal microbiota promoted NiONPs-induced liver fibrosis via effecting serum metabolism

Nickel oxide nanoparticles (NiONPs) are toxic heavy metal compounds that induce liver fibrosis and metabolic disorders. Current research shows that the intestinal microbiota regulates liver metabolism through the gut-liver axis. However, it is unclear whether NiONPs affect the intestinal microbiota and the relationship between microbiota and liver metabolic disorders. Therefore, in this study, we established liver fibrosis model by administering 0.015, 0.06 and 0.24 mg/mL NiONPs through tracheal instillation twice a week for 9 weeks in rats, then we collected serum and fecal sample for whole metabolomics and metagenomic sequencing. As the result of sequencing, we screened out seven metabolites (beta-D-glucuronide, methylmalonic acid, linoleic acid, phosphotidylcholine, lysophosphatidylinositol, docosapentaenoic acid and progesterone) that related to functional alterations (p < 0.05), and obtained a decrease of probiotics abundances (p < 0.05) as well as a variation of the microbiota enzyme activity (p < 0.05), indicating that NiONPs inhibited the proliferation of probiotics. As the result of correlation analysis, we found a positive correlation between differential metabolites and probiotics, such as lysophosphatidylinositol was positively correlated with Desulfuribacillus, Jeotgallibacillus and Rummeliibacillus (p < 0.05). We also found that differential metabolites had correlations with differential proteins and enzymes of intestinal microbiota, such as glucarate dehydratase, dihydroorotate dehydrogenase and acetyl-CoA carboxylase (p < 0.05). Finally, we screened six metabolic pathways with both differential intestinal microbiota enzymes and metabolites were involved, such as pentose and glucuronate interconversions, and linoleic acid metabolism. In vitro experiments showed that NiONPs increased the transcriptional expression of Col1A1 in LX-2 cells, while reducing the mRNA expression of serine/threonine activators, acetyl coenzyme carboxylase, and lysophosphatidylinositol synthase, and short chain fatty acid sodium butyrate can alleviate these variation trends. The results proved that the intestinal microbiota enzyme systems were associated with serum metabolites, suggesting that the disturbance of intestinal microbiota and reduction of probiotics promoted the occurrence and development of NiONPs-induced liver fibrosis by affecting metabolic pathways.

Fructus gardeniae ameliorates anxiety-like behaviors induced by sleep deprivation via regulating hippocampal metabolomics and gut microbiota.

Fructus gardeniae (FG) is a traditional Chinese medicine and health food for thousands of years of application throughout Chinese history and is still widely used in clinical Chinese medicine. FG has a beneficial impact on anxiety, depression, insomnia, and psychiatric disorders; however, its mechanism of action requires further investigation. This study aimed to investigate the effects and mechanisms of FG on sleep deprivation (SD)-induced anxiety-like behavior in rats. A model of SD-induced anxiety-like behavior in rats was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). This was accompanied by neuroinflammation and metabolic abnormalities in thehippocampus and disturbance of intestinal microbiota. However reduced SD-induced anxiety-like behavior and decreased levels of pro-inflammatory cytokines including TNF-α and IL-1β were observed in the hippocampus of rats after 7 days of FG intervention. In addition, metabolomic analysis demonstrated that FG was able to modulate levels of phosphatidylserine 18, Phosphatidylinositol 18, sn-glycero-3-phosphocholine, deoxyguanylic acid, xylose, betaine and other metabolites in the hippocampus. The main metabolic pathways of hippocampal metabolites after FG intervention involve carbon metabolism, glycolysis/gluconeogenesis, pentose phosphate, and glycerophospholipid metabolism. 16S rRNA sequencing illustrated that FG ameliorated the dysbiosis of gut microbiota in anxious rats, mainly increased the abundance of Muribaculaceae and Lactobacillus, and decreased the abundance of Lachnospiraceae_NK4A136_group. In addition, the correlation analysis demonstrated that there was a close relationship between hippocampal metabolites and intestinal microbiota. In conclusion, FG improved the anxiety behavior and inhibited of neuroinflammation in sleep-deprived rats, and the mechanism may be related to the FG regulation of hippocampal metabolites and intestinal microflora composition.

The Damage of the Crayfish (Procambarus Clarkii) Digestive Organs Caused by Citrobacter Freundii Is Associated With the Disturbance of Intestinal Microbiota and Disruption of Intestinal-Liver Axis Homeostasis.

As a common conditional pathogenic bacterium in nature, C. freundii has posed a threat to crayfish culture and may infect humans through consumption. However, the pathogenic mechanism of C. freundii in crayfish remains unknown, which poses difficulties for the prevention and control of the bacterium. In this study, the effects of C. freundii on the digestive organs, intestine and hepatopancreas, of crayfish were investigated by high-throughput sequencing technology combined with histological analysis and flow cytometry. The findings suggested that C. freundii caused disruption of the intestinal microbiota, leading to intestinal inflammation and disrupting intestinal integrity. Meanwhile, C. freundii infection stimulates bile acid biosynthesis in the intestinal microbiota. Transcriptomic results showed significant upregulation of hepatopancreatic lipid degradation pathway and cytochrome P450-related pathways. Follow-up experiments confirmed a decrease in intracellular lipids and an increase in ROS and apoptosis. All the results indicated the disruption of intestinal-liver axis homeostasis due to disturbed intestinal microbiota may as a potential basis for C. freundii pathopoiesis in crayfish. These results provide new insights into the pathogenic molecular mechanisms of C. freundii in the infection of crayfish.

Gut microbiota and atopic dermatitis in children: a scoping review

BackgroundGut microbiota plays an important role in the development of atopic dermatitis (AD). We aimed to elucidate research trends in gut microbiota and AD in children, to provide evidence and insights to the clinical prevention and treatment of AD in children.MethodsA scoping literature review on the studies of gut microbiota and AD were conducted. Two authors independently searched Pubmed et al. databases for studies focused on gut microbiota and AD in children up to January 15, 2022. The literatures were screened and analyzed by two reviewers.ResultsA total of 44 reports were finally included and analyzed. Current researches have indicated that abnormal human microecology is closely associated with AD, and the disturbance of intestinal microbiota plays an important role in the occurrence and development of AD. Probiotics can correct the microbiota disorder, have the functions of regulating immunity, antioxidant, and help to restore the microecological homeostasis. However, there is still a lack of high-quality research reports on the efficacy and safety of probiotics in the prevention and treatment of AD in children.ConclusionsThe changes of gut microbiota are essential to the development of AD in children, which may be an effective target for the prevention and treatment of AD. Future studies with larger sample size and rigorous design are needed to elucidate the effects and safety of probiotics in AD.

Microbiota from patients with ulcerative colitis promote colorectal carcinogenesis in mice

Objectives: Long-term ulcerative colitis (UC) is associated with both dysbiosis in intestinal microbiota and predisposition to colorectal cancer. In this study, we investigated whether microbiota from patients with UC could increase colorectal carcinogenesis in mice, generated by azoxymethane through intraperitoneal injection.Methods: Mice were gavaged twice per week with intestinal microbiota from patients with UC or healthy individuals. Intestinal tissues were collected from mice and compared by histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, Western blot, and flow cytometry analyses. Quantification of bacteria in feces was performed using 16 S ribosomal RNA gene selective quantitative polymerase chain reaction.Results: Compared with mice fed microbiota from healthy controls, increased tumorigenesis was observed in mice gavaged with microbiota from patients with UC, including a higher number of colon adenoma and a significantly higher proportion of grade dysplasia. Consistent with tumorigenesis, mice gavaged with microbiota from patients with UC showed an increased expression of Ki67 and proliferating cell nuclear antigen. In addition, an increased expression of cytokines and more abundant presence of T helper cells types 1 and 17 was observed in mice receiving microbiota from patients with UC. Moreover, a decrease in the abundance of short-chain fatty acids was detected in the feces, as well as an altered intestinal microbial composition in mice fed with microbiota from patients with UC.Conclusions: Fecal microbiota from patients with UC exacerbate tumorigenesis in mice. The disturbance of intestinal microbiota and activation of T helper cells types 1 and 17 cytokines caused by gavaging microbiota from patients with UC both contributed to intestinal carcinogenesis.

Effects of probiotics on loperamide-induced constipation in rats

The role of probiotics in mitigating constipation, gut immunity, and gut microbiota has not been well studied. We aimed to evaluate the effects of probiotics on loperamide (LP)-induced constipation in Sprague–Dawley rats. Altogether, 150 male Sprague–Dawley rats (age 8 weeks) were used in the experiments following a 12-day acclimatisation period and were randomly divided into three treatment groups (groups 1, 2, and 3). Spastic constipation was induced via oral LP administration (3 mg/kg) for 6 days, 1 h before administering each test compound in groups 1 and 2. A probiotic solution (4 mL/kg body weight) was orally administered once a day for 6 days in group 2. In group 1, a phosphate buffer solution was orally administered once a day for 6 days, 1 h after each LP administration. In group 3, a phosphate buffer solution was orally administered once a day for 6 days. In the probiotic group, faecal parameters improved; faecal n-butyric acid, acetic acid, and IgA concentrations were increased; intestinal transit time was shortened; and disturbance of intestinal microbiota was inhibited. Our findings suggest that this probiotic was useful in improving various symptoms caused by constipation.

Sildenafil ve Bacillus Clausii’nin Metotreksat Bağlı Mukozitin Önlenmesindeki Rolü: Preklinik Çalışma

Objective: Methotrexate (MTX) is a commonly used chemotherapeutic agent in clinical oncology practice and in treatment of autoimmune diseases. The major side effect during treatment is mucositis. Recently published studies reported that this effect may be due to direct intestinal epithelial injury and disturbance of intestinal microbiota. In this study, we aimed to characterize the intestinal histological changes caused by MTX and to investigate the effects and safety of Sildenafil and probiotic Bacillus clausii on intestinal mucositis in a rat model. Materials and Methods: The rats were divided in 4 groups; Group1(n=8) received MTX + B. clausii, Group 2 (n=8) received only MTX, Group3 (n=8) received MTX + Sildenafil and Group 4 (n=7) was served as control (received no treatment). Results: The rate of villus atrophy, villous fusion and erosion in the MTX + B. clausii group were found to be statistically significantly lower than in the MTX group and the MTX + Sildenafil group. Conclusion: The study demonstrated the effect of B. clausii on repairing of intestinal mucosa after MTX-treatment. The better understanding of the effects of probiotics on intestinal mucosal protection may lead to new therapeutic approaches in chemotherapy-induced mucositis.

Disturbances of intestinal microbiota in autism spectrum disorders: new horizons in search for pathogenetic approaches to therapy. Рart 3. Рotential strategies of influence on gut-brain axis for correction of symptoms of autism spectrum disorders

The third part of the literature review on the role of intestinal microbiota disturbances in the pathogenesis of autism spectrum disorders (ASD) is devoted to the analysis of published literature on possible interventional approaches for intestinal microbiota in ASD and the evaluation of the effectiveness of various types of interventions that have been studied in experiment and in clinical practice. Presented are available data on the possibility of correcting the intestinal microbiota in ASD with diet, taking pre- and probiotics, antibiotic therapy, as well as the effectiveness of transplantation of intestinal microbiota. An analysis of published data suggests that further development of approaches for correcting intestinal dysbiosis in ASD may provide safe and probably effective strategy for behavioral symptoms, but this requires further randomized controlled trials to confirm efficacy and safety from the perspective of evidence-based medicine, since available to date studies are small and scattered, and therefore they can only be considered preliminary.

Probiotics for the prevention of Hirschsprung-associated enterocolitis: a systematic review and meta-analysis.

Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung's disease. HAEC is reported to occur in 6-50% of patients preoperatively and in 2-35% postoperatively. The exact cause of HAEC is not fully understood, but disturbances of intestinal microbiota have recently been reported in patients with HAEC. In recent years, the administration of probiotics has been proposed to reduce the incidence of HAEC. We conducted a systematic review and meta-analysis to determine the effect of probiotics on postoperative HAEC. A systematic literature search for relevant articles was performed in four databases using the combinations of following terms "probiotics", "microbiota", "enterocolitis", "Lactobacillus", "Bifidobacterium", "Saccharomyces", "Streptococcus", and "Hirschsprung disease/Hirschsprung's disease" for studies published between 2002 and 2017. The relevant cohorts of the effect of probiotics in postoperative patients were systematically searched for clinical outcomes. Odds ratio (OR) or standard mean difference (SMD) with 95% confidence intervals (CI) were calculated using standardized statistical methodology. The search strategy identified 1274 reports. Overall, five studies met defined inclusion criteria, reporting a total of 198 patients. Two studies were prospective multicenter randomized control trials. Lactobacillus, Bifidobacterium, Streptococcus, and Enterococcus were used as probiotics. The incidence of HAEC with/without probiotics was 22.6 and 30.5%, respectively, but this was not statistically different (OR 0.72; 95% CI 0.37-1.39; P = 0.33). This study shows that the administration of probiotics was not associated with a significant reduction in the risk of HAEC. Additional studies are required to understand more fully the role of microbiota and complex interactions that cause HAEC. With increasing knowledge of the role of microbiota in HAEC, we are likely to understand better the potential benefits of probiotics in this disease.

Characterization of Intestinal Microbiomes of Hirschsprung's Disease Patients with or without Enterocolitis Using Illumina-MiSeq High-Throughput Sequencing.

Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung’s disease (HD). Although the pathological mechanisms are still unclear, studies have shown that HAEC has a close relationship with the disturbance of intestinal microbiota. This study aimed to investigate the characteristics of the intestinal microbiome of HD patients with or without enterocolitis. During routine or emergency surgery, we collected 35 intestinal content samples from five patients with HAEC and eight HD patients, including three HD patients with a history of enterocolitis who were in a HAEC remission (HAEC-R) phase. Using Illumina-MiSeq high-throughput sequencing, we sequenced the V4 region of bacterial 16S rRNA, and operational taxonomic units (OTUs) were defined by 97% sequence similarity. Principal coordinate analysis (PCoA) of weighted UniFrac distances was performed to evaluate the diversity of each intestinal microbiome sample. The microbiota differed significantly between the HD patients (characterized by the prevalence of Bacteroidetes) and HAEC patients (characterized by the prevalence of Proteobacteria), while the microbiota of the HAEC-R patients was more similar to that of the HAEC patients. We also observed that the specimens from different intestinal sites of each HD patient differed significantly, while the specimens from different intestinal sites of each HAEC and HAEC-R patient were more similar. In conclusion, the microbiome pattern of the HAEC-R patients was more similar to that of the HAEC patients than to that of the HD patients. The HD patients had a relatively distinct, more stable community than the HAEC and HAEC-R patients, suggesting that enterocolitis may either be caused by or result in a disruption of the patient’s uniquely adapted intestinal flora. The intestinal microbiota associated with enterocolitis may persist following symptom resolution and can be implicated in the symptom recurrence.

Effects of Salmonella infection on hepatic damage following acute liver injury in rats

Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. Oral supplementation with Salmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury. The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury (P<0.01); The peyer's patch CD3+ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group (P<0.05). S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation. Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe. Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

What could probiotic do for us?

Gastrointestinal microbes play important roles in the health and disease of the host. There are many documented evidences which demonstrated that disturbance of intestinal microbiota is linked to the risk of developing infectious, inflammatory and allergic diseases. Human intestine is home for a complex consortium of 1013–1014 microbial cells. Interactions between the intestinal microbes, pathogens and the host lead to exclusion of toxins (mycotoxins) and pathogens (colonization resistance), interference in disease progression as demonstrated in the prevention of oral infection, dental caries, diarrhoeas (Antibiotic Associated Diarrhoea, Travellers’ Diarrhoea and Rotavirus Diarrhoea), postoperative infection, respiratory infection and certain cancers. The group of beneficial intestinal microbes termed probiotics alter intestinal epithelial cell tight junction and immunological functions. Lately, laboratory and clinical studies demonstrated gut-brain axis communication and intestinal microbial (both pathogens and probiotics) modulation of host psycho-neuroimmunological functions, in relation to depression, anxiety and memory dysfunction. These open up many possibilities of probiotics supplementation for moderating intestinal microbiota as an approach in disease prevention and treatment.

Clostridium difficile infection and gut microbiota

Clostridium difficile infection (CDI) is associated with disturbance of intestinal microbiota. Microbiota of CDI patients usually shows decreased diversity, increase of facultative anaerobes, and decreased levels of bifidobacteria, Bacteroidetes, Lachnospiraceae, and butyrate-producing bacteria. Studies including symptomatic, asymptomatic, recurrent, and fecal therapy-treated patients could result in the recognition of microbial markers for CDI risk or could provide the combination of beneficial microbes for a C. difficile-specific probiotic.