Alterations In Intestinal Microflora Research Articles

Metabolic changes before and after weaning in Dezhou donkey foals in relation to gut microbiota.

Weaning is undoubtedly one of the most crucial stages in the growth and development of all mammalian animals, including donkey foals. Weaning is a dynamic and coordinated process of the body, which is closely associated with the health, nutrition, and metabolism of the host. Many studies have shown that the intestinal microbiota and serum metabolites of mammals exhibit different changes during lactation, weaning, and postweaning. However, the alterations in serum metabolites in donkey foals before and postweaning and the correlation between serum metabolites and intestinal microbiota are largely unknown. This study is based on the fecal 16S rRNA and serum metabolomes of Dezhou donkey foals. In total, 10 samples (fecal and serum) were collected during the following three stages: before weaning (F.M.1), during weaning (F.M.3), and postweaning (F.M.6). To study the alterations in intestinal microflora, serum metabolites, and their correlation before and postweaning. We found that with the growth and weaning progress of donkey foals, the intestinal microbiota of donkey foals underwent obvious changes, and the diversity of fecal bacteria increased (Chao1 and Shannon indexes). The main intestinal microbial flora of donkey foals include Bacteroides and Firmicutes. We found many microbiota that are associated with immunity and digestion in the postweaning group, such as Verrucomicrobiales, Clostridia, Oscillospiraceae, Akkermansia, and Rikenellaceae, which can be considered microbial markers for the transition from liquid milk to solid pellet feed. Clostridia and Oscillospiraceae can produce organic acids, including butyric acid and acetic acid, which are crucial for regulating the intestinal microecological balance of donkeys. Furthermore, the metabolome showed that the serum metabolites enriched before and postweaning were mainly related to arachidonic acid metabolism and riboflavin metabolism. Riboflavin was associated with the development of the small intestine and affected the absorption of the small intestine. We also found that the changes in the gut microbiome of the foals were significantly correlated with changes in serum metabolites, including lysophosphatidylcholine (LPC; 12,0) and positively correlated with Lachnoclostridium and Roseburia. To summarize, this study provides theoretical data for the changes in the intestinal microbiome and serum metabolism during the entire weaning period of donkey foals.

Virulent Porphyromonas gingivalis as the root cause of chronic inflammation‐a Chronic Oral Health Perspective

AbstractOral health professionals are the forefront of preventing and treating not only dental and periodontal diseases, but also a growing list of systemic conditions associated with specific periodontal pathogens such as P. gingivalis (Pg). The oral‐systemic connection offers dental professionals an opportunity to positively influence patients’ overall health. Armed with the ability to transform its own environment and the entire periodontal microbiome, as well as modify the host response, the influence of Pg extends beyond the oral cavity. Beyond the neuroinflammatory effects discussed in this session it is capable of both releasing complex virulence factors/toxins and translocating and invading distant tissues and organs and is involved in the pathogenesis of systemic diseases including cardiovascular disease, atherosclerosis, hypertension, myocarditis, and myocardial infarction. This periodontal pathogen also impacts autoimmune diseases including rheumatoid arthritis; neurodegenerative diseases such as Alzheimer’s disease and AD‐related brain atrophy; several cancers‐oral, esophageal, and pancreatic; and metabolic diseases such as diabetes mellitus. Pg by limiting the complement cascade and restraining leukocyte death by activating and exploiting the C5a‐receptor signaling pathway. Another viable conduit in systemic dysbiosis and immune dysfunction is the translocation of Pg with its microbiome‐altering abilities and its coaggregation pathobiont actions found in the gut flora. Studies on murine models that introduced Pg into the gut demonstrated an altered intestinal microflora and increased manifestation or aggravation of liver disease, arthritis, including an increase in the production of proinflammatory cytokines observed at both the intestinal and extra‐intestinal levels. Dental professionals will most likely be one of the major healthcare delivery systems to bring a paradigm shift in healthcare and medicine using novel companion diagnostics and treatments to early screening and treatment of virulent Pg infections in the general population thereby greatly reducing the onset of multiple major systemic inflammatory driven chronic diseases. Dental professionals will most likely be one of the major healthcare delivery systems to bring a paradigm shift in healthcare and medicine by using novel companion diagnostics and treatments to early screening and treatment of virulent Pg infections in the general population thereby greatly reducing the onset of multiple major systemic inflammatory driven chronic diseases.

Lactoferrin for the postoperative management of term neonates after gastrointestinal surgery.

Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be due in part to disruption of the integrity of the gut and its altered intestinal microflora. Lactoferrin is a whey protein found in milk and is an important innate mammalian defence mechanism. Lactoferrin has been reported to have antimicrobial and anti-inflammatory properties. It has also been reported to help establish a healthy gut microflora and aid in the intestinal immune system. Lactoferrin supplementation has been reported to decrease sepsis in preterm infants. There may be a role for lactoferrin to reduce the incidence of sepsis, thus reducing morbidity and mortality and improving enteral feeding in postoperative term neonates. The primary objective of this review was to evaluate the efficacy of administering lactoferrin on the incidence of sepsis and mortality in term neonates after gastrointestinal surgery. The secondary objective was to assess the impact of administering lactoferrin on time to full enteral feeds, the intestinal microflora, duration of hospital stay, and mortality before discharge in the same population. The Cochrane Neonatal Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase Ovid, CINAHL, the WHO ICTRP and ClinicalTrials.gov trials registries. The date of the last search was February 2023. There were no restrictions to language, publication year or publication type. We checked references of potentially relevant studies and systematic reviews. We planned to include randomised controlled trials that studied infants born at 37 or more weeks of gestation who had one or more episodes of gastrointestinal surgery within 28 days of birth, and compared administration of lactoferrin with a placebo. We used standard Cochrane methodological procedures. We planned to use the GRADE approach to assess the certainty of evidence for each outcome. We identified no published randomised controlled studies that assessed the efficacy of lactoferrin for the postoperative management of term neonates following gastrointestinal surgery. There is currently no evidence available from randomised controlled trials to show whether lactoferrin is effective or ineffective for the postoperative management of term neonates after gastrointestinal surgery. There is a need for randomised controlled trials to be performed to assess the role of lactoferrin in this setting.

Alteration of intestinal microflora by the intake of millet porridge improves gastrointestinal motility

Foxtail millet (Setaria italica) has a long history of treating gastrointestinal ailments in China; however, little is known about the functional mechanism driving its therapeutic effects. The primary edible form of millet is porridge. This study investigates the effects of millet porridge on diphenoxylate-induced constipation and intestinal microflora in mice. Fifty mice were randomly divided into five groups: normal control group, constipation model group, and low-dose, medium-dose, and high-dose millet porridge groups. After 14 days of millet porridge gavage, constipation was induced and measured. The results showed that millet porridge prevented constipation by increasing the water content of feces, shortened the time of the first melena defecation, promoted gastric emptying, and improved the rate of gastrointestinal propulsion. Millet porridge also dose-dependently increased levels of Bifidobacterium and Lactobacillus and decreased levels of Escherichia coli, Enterococcus, and Bacteroides in the intestine. These results show that millet porridge could accelerate intestinal motility and change the proportions of intestinal flora and that it has a potent prebiotic effect.

Intestinal flora alterations in patients with ulcerative colitis and their association with inflammation.

Ulcerative colitis (UC), which is a type of inflammatory bowel disease, is a chronic intestinal disorder of multifactorial etiology. Numerous studies have indicated an association between UC and intestinal bacteria. However, a limited number of studies regarding the expression of interleukin-17 (IL-17) and interleukin-23 (IL-23) in association with intestinal bacteria have been performed. The aim of the current study was to investigate the gut microbiota alterations in patients with UC, at a number of taxonomic levels, and their relationship with intestinal inflammation by analyzing the protein expression of IL-17 and IL-23. Specimens were collected from 10 healthy controls and 16 patients with UC. A histological examination was performed in colonic tissues, IL-17 and IL-23 protein expression was detected by immunohistochemistry, fecal samples were sequenced using 16S rDNA sequencing and bioinformatics analysis was performed. The UC group exhibited an increased histological score (P<0.01) and upregulated IL-17 and IL-23 expression (P<0.01). At the order level, the bacterial diversity of the UC group was decreased. β-diversity analyses, including principal component analysis, principal coordinate analysis and non-metric multidimensional scaling, demonstrated that the two groups of samples were separated into two taxonomic categories, as distinct variations were observed in the analysis of group differences (P=0.001). Regarding the differences in species composition between the groups, Enterococcus was indicated to be the species with the greatest difference in abundance compared with the healthy control group (P<0.01), followed by Lactobacillus (P<0.05), Escherichia-Shigella (P<0.05), Bifidobacterium and Bacteroides. In addition, the average optical density of IL-17 was positively correlated with the histological score (ρ=0.669; P=0.035), Enterococcus (r=0.843; P<0.001), Lactobacillus (r=0.737; P=0.001), Bifidobacterium (r=0.773; P<0.001) and Escherichia-Shigella (r=0.663; P=0.005), and the average optical density of IL-23 was positively correlated with the histological score (ρ=0.733; P=0.016), Enterococcus (r=0.771; P<0.001), Lactobacillus (r=0.566; P=0.022), Bifidobacterium (r=0.517; P=0.041) and Escherichia-Shigella (r=0.613; P=0.012). The results of the present study indicated that the intestinal microbiota of patients with UC differed from that of healthy controls at multiple taxonomic levels. The alterations of the intestinal microflora were closely associated with the degree of inflammation. The IL-23/IL-17 axis, as a key factor in the development of UC, maybe associated with the alterations of intestinal microflora. The interaction between intestinal microflora and the IL-23/IL-17 axis may serve an important role in the pathogenesis of UC.

Role of maternal melatonin in the development of the microbiome in children

This review presents literature data on the role of melatonin in regulating the composition of the microbiota and on the variety of functions it performs that are synchronized with the circadian rhythm of vital activity of the body. During pregnancy, the restructuring of the intestinal, vaginal and placental microbiota is provided by a significant increase in the production of epiphyseal melatonin, which contributes to the creation of optimal conditions for the development of microflora in early ontogenesis. In the absence of circadian production of melatonin, a pregnant woman retains dysbiosis, which determines the transmission of altered intestinal microflora to the fetus and subsequent metabolic dysregulation in the childs body.

Bacteria\u2010derived ferrichrome inhibits tumor progression in sporadic colorectal neoplasms and colitis\u2010associated cancer

BackgroundColorectal cancers develop through several pathways, including the adenoma–carcinoma sequence and colitis-associated carcinogenesis. An altered intestinal microflora has been reported to be associated with the development and progression of colorectal cancer via these pathways. We identified Lactobacillus casei-derived ferrichrome as a mediator of the bacterial anti-tumor effect of colorectal cancer cells through the upregulation of DDIT3. In this study, we investigated the anti-tumor effects of ferrichrome on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer.MethodsSRB and MTT assays were performed to assess growth inhibition in vitro. Eighteen organoids were prepared from biopsy specimens obtained by colonoscopy. An AOM-DSS carcinogenesis model and xenograft model of colorectal cancer cells were generated for the assessment of the tumor suppressive effect of ferrichrome in vivo.ResultsFerrichrome inhibited the cell growth of colorectal cancer cells in vitro and in in vivo xenograft models. Ferrichrome exerted a strong tumor-suppressive effect that was superior to that of currently available anti-tumor agents, including 5-FU and cisplatin, both in vitro and in vivo. The tumor-suppressive effect of the combination of ferrichrome and 5-FU was superior to that of single treatment with either drug. The tumor suppressive effects of ferrichrome were confirmed through the upregulation of DDIT3 in patient-derived organoids of adenoma and carcinoma. Ferrichrome inhibited the tumor progression in the AOM-DSS model while exhibiting no anti-inflammatory effect in the DSS-colitis model, suggesting that ferrichrome inhibited cancer cells, but not a precancerous condition, via the colitis-associated pathway.ConclusionsFerrichrome exerts a tumor suppressive effect on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. The anti-tumor effect of ferrichrome was mediated by the upregulation of DDIT3, and was superior to that of 5-FU or cisplatin. These results suggest that Lactobacillus brevis-derived ferrichrome may be a candidate anti-tumor drug for the treatment of colorectal neoplasms.

Chitosan Ameliorates DSS-Induced Ulcerative Colitis Mice by Enhancing Intestinal Barrier Function and Improving Microflora.

Ulcerative colitis (UC) has been identified as one of the inflammatory diseases. Intestinal mucosal barrier function and microflora play major roles in UC. Modified-chitosan products have been consumed as effective and safe drugs to treat UC. The present work aimed to investigate the effect of chitosan (CS) on intestinal microflora and intestinal barrier function in dextran sulfate sodium (DSS)-induced UC mice and to explore the underlying mechanisms. KM (Kunming) mice received water/CS (250, 150 mg/kg) for 5 days, and then received 3% DSS for 5 days to induce UC. Subsequently, CS (250, 150 mg/kg) was administered daily for 5 days. Clinical signs, body weight, colon length, and histological changes were recorded. Alterations of intestinal microflora were analyzed by PCR-DGGE, expressions of TNF-α and tight junction proteins were detected by Western blotting. CS showed a significant effect against UC by the increased body weight and colon length, decreased DAI (disease activity index) and histological injury scores, and alleviated histopathological changes. CS reduced the expression of TNF-α, promoted the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1 to maintain the intestinal mucosal barrier function for attenuating UC in mice. Furthermore, Parabacteroides, Blautia, Lactobacillus, and Prevotella were dominant organisms in the intestinal tract. Blautia and Lactobacillus decreased with DSS treatment, but increased obviously with CS treatment. This is the first time that the effect of original CS against UC in mice has been reported and it is through promoting dominant intestinal microflora such as Blautia, mitigating intestinal microflora dysbiosis, and regulating the expressions of TNF-α, claudin-1, occludin, and ZO-1. CS can be developed as an effective food and health care product for the prevention and treatment of UC.

Effect of Probiotic Use on Adverse Events in Adult Patients with Inflammatory Bowel Disease: a Retrospective Cohort Study.

Alterations of intestinal microflora are involved in the pathogenesis and natural history of inflammatory bowel diseases (IBDs). Manipulation of human gut microbiota with probiotics may be a therapeutic option. In this retrospective cohort study, the benefits of probiotic use in reducing adverse events were analyzed. Data from clinical charts of IBD patients followed up for at least 36months were retrieved. The occurrence of adverse events including the need for systemic steroids, hospitalization, and surgery related to IBD was analyzed according to age, gender, body mass index, treatments, IBD phenotype, disease duration, and probiotic use. The amount of probiotic use was calculated as the ratio of time under probiotic treatment to the disease duration starting from the date of the first probiotic administration and expressed as a percentage. Patients were stratified according to the percentage of probiotic use as ≤ 24%, 25-74%, and ≥ 75%, and the number of adverse events per patient-years was calculated. Results were adjusted for Crohn's disease (CD) and ulcerative colitis (UC) by multivariate analysis including study variables. Data from 200 patients (78 CD, 122 UC; 117 females; mean age 40.6 ± 15.3years; mean disease duration 12.1 ± 8.7years) were available. CD patients taking probiotics for 25-74% of the disease duration experienced a 64% reduction in total adverse events. The need for systemic steroids, hospitalization, and surgery dropped to zero events per person-year in UC patients and decreased by 93% (p < 0.001) in CD patients taking probiotics for ≥ 75% of the disease duration. Our findings suggest that the use of probiotics may be an additional therapeutic tool in patients with IBD.

Effects of garlic polysaccharide on alcoholic liver fibrosis and intestinal microflora in mice

Context: Alcoholic liver fibrosis (ALF) is treatable and reversible consequence of liver disease. Intestinal microflora plays an important role in the progression of liver disease. Garlic (Allium sativum L. [Amaryllidaceae]) has been consumed as a traditional medicine to treat liver injury.Objective: To investigate the effects of garlic polysaccharide (GP) on ALF and intestinal microflora in mice.Materials and methods: KM mice were orally administered with alcohol (56%, 6 mL/kg) for 30 d to establish ALF model, and divided into four groups together with control group (water only). Hugan tablet (60 mg/kg) or GP (250 and 150 mg/kg) were given 5 h after each dose of alcohol. Biochemical markers in serum and liver homogenate were determined with kits. Alteration of intestinal microflora, and protein expressions of TGF-β1, TNF-α and decorin were detected.Results: In GP-H group, ALT and AST decreased to 18.85 ± 4.71 U/L and 40.84 ± 7.89 U/L. MDA, TC, TG and LDL-C decreased to 2.32 ± 0.86 mmol/mg, 0.21 ± 0.12 mmol/L, 0.96 ± 0.31 mmol/L and 0.084 ± 0.027 mmol/L. SOD, GSH-Px and GSH increased to 118.32 ± 16.32 U/mg, 523.72 ± 64.20 U/mg and 0.56 ± 0.05 mg/g. Ratios of TGF-β1 and TNF-α decreased to 0.608 ± 0.170 and 1.057 ± 0.058, decorin increased to 2.182 ± 0.129. Lachnospiraceae and Lactobacillus increased, Facklamia and Firmicutes decreased with GP pretreatment.Discussion and conclusions: Intestinal microflora provides novel insight into the mechanisms of GP that may be used to treat ALF and intestinal microflora dysbiosis.

Effects of polysaccharide from Physalis alkekengi var. francheti on liver injury and intestinal microflora in type-2 diabetic mice

Context: Diabetic liver injury is a serious diabetic complication. The alterations of intestinal microbiota play an important role in induction and promotion of liver injury progression. Physalis alkekengi L. var. francheti (Mast.) Makino (Solanaceae) has been used as a water decoction for treating diabetes.Objective: To study the effects of a polysaccharide (PPSB) from Physalis alkekengi var. francheti on liver injury and intestinal microflora in type-2 diabetic mice.Materials and methods: Streptozotocin (160 mg/kg) was injected i.p. for 3 days to build model. The diabetic mice were randomly divided into four groups together with control group (10 mice in each group). The doses of PPSB were 50 and 100 mg/kg, respectively. After 5 weeks administration, level of blood glucose, ALT and AST were measured. Alterations of intestinal microflora, and protein expression of TGF-β1, TNF-α and DCN were detected.Results: Level of blood glucose decreased from (25.38 ± 2.21) mmol/L to (18.01 ± 2.53) mmol/L, ALT and AST decreased to (24.67 ± 4.86) U/L and (30.84 ± 7.50) U/L in PPSB-H group. Lactobacillus, Clostridium butyricum, and Bacteroides increased remarkably with increasing concentration of PPSB, but Enterobacter was inhibited. The relative expression of TGF-β1 and TNF-α decreased to (0.70 ± 0.17) and (0.39 ± 0.06), and the expression of DCN increased to (0.65 ± 0.13).Discussion and conclusions: Probiotics have been promoted by PPSB, and protein expressions have been modulated in the progression of liver injury. PPSB could be used as a natural agent for treating diabetic liver injury and intestinal microflora imbalance.

Qualitatively and quantitatively investigating the regulation of intestinal microbiota on the metabolism of panax notoginseng saponins

Ethnopharmacological relevanceIntestinal microflora plays crucial roles in modulating pharmacokinetic characteristics and pharmacological actions of active ingredients in traditional Chinese medicines (TCMs). However, the exact impact of altered intestinal microflora affecting the biotransformation of TCMs remains poorly understood. Aims of the studyThis study aimed to reveal the specific enterobacteria which dominate the metabolism of panax notoginseng saponins (PNSs) via exploring the relationship between bacterial community structures and the metabolic profiles of PNSs. Materials and methods2, 4, 6-Trinitrobenzenesulphonic acid (TNBS)-challenged and pseudo germ-free (pseudo GF) rats, which prepared by treating TNBS and antibiotic cocktail, respectively, were employed to investigate the influence of intestinal microflora on the PNS metabolic profiles. Firstly, the bacterial community structures of the conventional, TNBS-challenged and pseudo GF rat intestinal microflora were compared via 16S rDNA amplicon sequencing technique. Then, the biotransformation of protopanaxadiol-type PNSs (ginsenoside Rb1, Rb2 and Rd), protopanaxatriol-type PNSs (ginsenoside Re, Rf, Rg1 and notoginsenoside R1) and Panax notoginseng extract (PNE) in conventional, TNBS-challenged and pseudo GF rat intestinal microbiota was systematically studied from qualitative and quantitative angles based on LC-triple-TOF/MS system. Besides, glycosidases (β-glucosidase and β-xylosidase), predominant enzymes responsible for the deglycosylation of PNSs, were measured by the glycosidases assay kits. ResultsSignificant differences in the bacterial community structure on phylum, class, order, family, and genera levels were observed among the conventional, TNBS-challenged and pseudo GF rats. Most of the metabolites in TNBS-challenged rat intestinal microflora were identified as the deglycosylation products, and had slightly lower exposure levels than those in the conventional rats. In the pseudo GF group, the peak area of metabolites formed by loss of glucose, xylose and rhamnose was significantly lower than that in the conventional group. Importantly, the exposure levels of the deglycosylated metabolites were found have a high correlation with the alteration of glycosidase activities and proteobacteria population. Several other metabolites, which formed by oxidation, dehydrogenation, demethylation, etc, had higher relative exposure in pseudo GF group, which implicated that the up-regulation of Bacteroidetes could enhance the activities of some redox enzymes in intestinal microbiota. ConclusionThe metabolism of PNSs was greatly influenced by intestinal microflora. Proteobacteria may affect the deglycosylated metabolism of PNSs via regulating the activities of glycosidases. Besides, up-regulation of Bacteroidetes was likely to promote the redox metabolism of PNSs via improving the activities of redox metabolic enzymes in intestinal microflora.

Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate.

Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, PubMed was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.

Dietary squid ink polysaccharides ameliorated the intestinal microflora dysfunction in mice undergoing chemotherapy.

Gastrointestinal mucositis and infection by chemotherapy treatment are associated with alteration of intestinal microflora and bacterial translocation due to the potential damage induced by anti-cancer drugs on the intestinal barrier and microbiota homeostasis. This study aimed to investigate the protective effect of dietary polysaccharides on chemotherapy induced intestinal microflora dysfunction. In the current contribution, with a mouse model intraperitoneally injected with 50 mg kg(-1) of cyclophosphamide (Cy) for 2 days, we revealed that polysaccharides from the ink of Ommastrephes bartrami (OBP) altered the intestinal microflora composition. OBP retarded the excessive growth of intestinal bacteria induced by cyclophosphamide, based on 16S rRNA gene (16S rDNA) quantification. The clone libraries of intestinal bacteria 16S rDNA were used to decipher the difference in bacterial community structures in different groups of mice. Followed by RFLP evaluation and OTU abundance analysis, they imply that OBP changed the intestinal microflora composition, in which the quantity of probiotic Bifidobacterium got up-regulated but Bacteroidetes decreased in mice undergoing chemotherapy. Our results may have important implications for OBP as a functional food component or nutrient against chemotherapy induced intestinal injury and potential pathogenic intestinal disorders involving inflammation and infection.

The Pediatric Infectious Disease Journal® Newsletter

The Pediatric Infectious Disease Journal® Newsletter

Modulation of mucosal immune responses to Clostridium difficile by probiotic bacteria (P3073)

Abstract Commensal bacteria play a critical role in maintaining intestinal epithelium and mucosal immune homeostasis. Alterations in intestinal microflora predispose mammalian hosts to infection with pathogens such as Clostridium difficile, which has recently re-emerged as a pathogen causing nosocomial diarrhea, colitis and death. We investigated the mechanisms by which the probiotic VSL#3 ameliorates C. difficile-associated disease (CDAD) in mice. Oral VSL#3 administration reduced disease activity, body weight loss, and colonic inflammatory lesions after infection. Probiotic treatment also decreased Th17 and IL-17-producing TCRγδ cell populations at the colonic lamina propria as well as production of IL-17 and IL-1β in the colonic mucosa. Increased numbers of regulatory T cells (Treg) were seen in spleens of VSL#3-treated mice, which correlated to increased peroxisome proliferator-activated receptor γ (PPARγ) activity. PPARγ is a transcription factor and nuclear receptor that modulates immune responses and whose activation is essential for the maintenance of innate antimicrobial immunity in the colon. Mice treated with VSL#3 had an upregulation of calprotectin antimicrobial peptides S100A8 and S100A9 in the colon correlating to decreased fecal clostrial burden at day 4 post-infection. VSL#3 probiotic bacteria regulate colitis by increasing PPARγ activity and decreasing IL-17 responses and increase clostridial clearance by upregulating antimicrobial peptides in mice with CDAD.

Gut Microbiota and the Immune System: An Intimate Partnership in Health and Disease

In recent years there have been increased rates of autoimmune diseases, possibly associated to altered intestinal microflora. In this brief review article, after a description of the structure and function of the gut microbiota organ and its cross-talk with the human host, we give a report on findings indicating how the host immune system responds to bacterial colonization of the gastrointestinal tract. The disturbances in the bacterial microbiota will result in the deregulation of adaptive immune cells, which may underlie autoimmune disorders. The mammalian immune system, which seems to be designed to control microorganisms, could be instead influenced by microorganisms, as suggested in recent literature. Alterations in both the structure and function of intestinal microbiota could be one of the common causative triggers of autoimmune and/or autoinflammatory disorders.

Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high‐risk infants

Alterations in intestinal microflora have been linked to the development of allergic disease. Recent studies suggest that healthy infant immune development may depend on the establishment of a diverse gut microbiota rather than the presence or absence of specific microbial strains. We investigated the relationship between diversity of gut microbiota in the early postnatal period and subsequent development of eczema and atopy in the first year of life. Fecal samples were collected 1 wk after birth from 98 infants at high risk of allergic disease, who were followed prospectively to age 12 months. Fecal microbial diversity was assessed by terminal restriction fragment length polymorphism (T-RFLP) using restriction enzymes Sau96I and AluI, with a greater number of peaks representing greater diversity of bacterial communities. Microbial diversity at day 7 was significantly lower in infants with eczema at age 12 months as compared to infants without eczema (AluI mean number of peaks 13.1 vs. 15.5, p = 0.003, 95% CI for difference in means -3.9, -0.8; Sau96I 14.7 vs. 17.2, p = 0.03, 95% CI -4.9, -0.3). No differences were observed for atopic compared to non-atopic infants, or infants with two allergic parents compared to those with one or no allergic parent. A more diverse intestinal microbiota in the first week of life is associated with a reduced risk of subsequent eczema in infants at increased risk of allergic disease. Interventions that enhance microbial diversity in early life may provide an effective means for the prevention of eczema in high-risk infants.

Changes of Intestinal Microflora in Patients with Rheumatoid Arthritis during Fasting or a Mediterranean Diet

Background: Therapeutic dietary interventions are effective treatments for rheumatoid arthritis (RA). The mechanisms to affect inflammation and clinical outcome in rheumatoid arthritis are only partly understood. Alterations in intestinal microflora are believed to be associated with disease activity in RA. Aim: To evaluate changes in short-chain fatty acid (SCFA) profiles and clinical outcome in RA during medical fasting or mediterranean diet. Methods: Fifty consecutive in-patients from an Integrative Medicine Department were included in a prospective observational, non-randomised, clinical trial. Patients underwent a 7-day fasting (MF) therapy or a Mediterranean diet (MD) as part of a multimodal therapeutic treatment approach. Results: The mean Disease Activity Score (DAS-28) significantly decreased in both groups (p < 0.001) from 5.7 ± 0.9 to 4.1 ± 1.3 in the MF and from 5.4 ± 1.4 to 4.5 ± 1.3 in the MG group, with no significant difference between the groups (p = 0.115). VAS showed a consecutive decrease of pain in both study groups which was significantly higher in the fasting group on day 7 (p = 0.049). No significant differences between the study groups were found in the profile of total-fatty acids (p = 0.069), butyrate (p = 0.611) and propionate (p = 0.419). Measurement of acetate, however, showed significant differences (p = 0.044) with an increase from 17,4 ± 9.8 µmol/g to 21,4 ± 16.4 µmol/g in MF compared to a decrease from 15,2 ± 10.4 µmol/g to 13,8 ± 9.3 µmol/g in MD. There was no significant correlation between dietary induced changes of SCFA and changes of disease activity. Conclusion: Alterations in SCFA were found in terms of significant changes to increased acetate levels in the fasting group. A correlation between changes of SCFA from intestinal microflora and disease activity in RA could not be revealed. Further studies are needed in the field of dietary inducible changes of the intestinal microflora in patients with RA.

Human Intestinal Microbiota Gene Risk Factors for Antibiotic-Associated Diarrhea: Perspectives for Prevention

Antibiotic-associated diarrhea (AAD) is associated with altered intestinal microflora and other symptoms that may lead to possibly death. In critically ill patients, diarrhea increases rates of morbimortality. Assessing diarrhea risks is thus important for clinicians. For this reason, we conducted a hypothesis-generating study focused on AAD to provide insight into methods of prevention. We evaluated the hypothesis of predisposing factors within the resident intestinal microbiota in a cohort of outpatients receiving antibiotherapy. Among the pool of tested variables, only those related to bacterial 16S rRNA genes were found to be relevant. Complex statistical analyses provided further information: amid the bacteria 16S rRNA genes, eight were determined to be essential for diarrhea predisposition and characterized from the most important to the least. Using these markers, AAD risk could be estimated with an error of 2%. This molecular analysis offers new perspectives for clinical applications at the level of prevention.