Salmonella effector SpvB interferes with intracellular iron homeostasis via regulation of transcription factor NRF2.

Iron is a necessary nutrient for humans and nearly all bacterial species. During Salmonella infection, macrophages limit the availability of iron to intracellular pathogens in one of the central components of nutritional immunity. However, Salmonella also have mechanisms to interfere with the antimicrobial effect of host iron withdrawal and meet their own nutrient requirements by scavenging iron from the host. Here, we provide what is, to our knowledge, the first report that SpvB, a pSLT-encoded cytotoxic protein whose function is associated with the intracellular stage of salmonellosis, perturbs macrophage iron metabolism, thereby facilitating Salmonella survival and intracellular replication. In investigating the underlying mechanism, we observed that the Salmonella effector SpvB down-regulated nuclear factor erythroid-derived 2-related factor 2 (NRF2), and its C-terminal domain was necessary and sufficient for NRF2 degradation via the proteasome pathway. Decreased NRF2 expression in the nucleus resulted in a decrease in its transcriptional target ferroportin, encoding the sole macrophage iron exporter, thus ultimately decreasing iron efflux and increasing the intracellular iron content. Additionally, SpvB contributes to the pathogenesis of Salmonella including severe serum hypoferremia, increased splenic and hepatic bacterial burden, and inflammatory injury in vivo. Together, our observations uncovered a novel contribution of SpvB to Salmonella pathology via interference with host intracellular iron metabolism.-Yang, S., Deng, Q., Sun, L., Dong, K., Li, Y., Wu, S., Huang, R. Salmonella effector SpvB interferes with intracellular iron homeostasis via regulation of transcription factor NRF2.

Helicobacter pylori and extragastric diseases.

Many studies have been performed in the last year concerning the potential role of Helicobacter pylori in different extragastric diseases, reinforcing the idea that specific microorganisms may cause diseases even far from the primary site of infection. While the role of H. pylori on idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency has been well established, there is a growing interest in other conditions, such as cardiovascular, neurologic, dermatologic, obstetric, immunologic, and metabolic diseases. Concerning neurologic diseases, there is a great interest in cognitive impairment and neurodegeneration. The aim of this review was to summarize the results of the most relevant studies published over the last year on this fascinating topic.

Development of Probiotic Formulation for the Treatment of Iron Deficiency Anemia.

Probiotics are increasingly more present both as functional foods, and in pharmaceutical preparations with multiple levels of action that contribute to human health. Probiotics realize their positive effects with a proper dose, and by maintaining a declared number of probiotics cells by the expiration date. Important precondition for developing a probiotic product is the right choice of clinically proven probiotic strain, the choice of other active components, as well as, the optimization of the quantity of active component of probiotic per product dose. This scientific paper describes the optimization of the number of probiotics cells in the formulation of dietary supplement that contains probiotic culture Lactobacillus plantarum 299v, iron and vitamin C. Variations of the quantity of active component were analyzed in development batches of the encapsulated probiotic product categorized as dietary supplement with the following ingredients: probiotic culture, sucrosomal form of iron and vitamin C. Optimal quantity of active component L. plantarum of 50 mg, was selected. The purpose of this scientific paper is to select the optimal formulation of probiotic culture in a dietary supplement that contains iron and vitamin C, and to also determine its expiration date by the analysis of the number of viable probiotic cells.

Nationwide survey of Helicobacter pylori treatment for children and adolescents in Japan.

BACKGROUND: To prevent gastric cancer, a test-and-treat strategy for Helicobacter pylori has been proposed. This retrospective study assessed the clinical features, efficacy and safety of treatment for H. pylori infection in children and adolescents. METHODS: Questionnaires concerning the clinical features and treatment of H. pylori in children and adolescents were sent to doctors in 2013. It included questions on patient background, H. pylori-associated disease, first- and second-line treatment, success or failure of eradication, resistance to antibiotics, and occurrence of adverse events. In 2014, serious adverse events associated with treatment were analyzed. RESULTS: Invitation letters and questionnaires were sent to 1097 doctors, of whom 409 (37.3%) participated. Finally, 332 patients (mean age, 11.6 ± 3.4 years; male, n = 200) treated from 1997 to 2013 were analyzed. H. pylori-associated gastritis, iron deficiency anemia, and duodenal ulcer occurred most frequently. Success rates for first- and second-line treatments were 73.1% and 79.6%, respectively. Seventy-six H. pylori strains were analyzed for resistance to amoxicillin (AMPC) and clarithromycin (CAM), and 64 were analyzed for resistance to metronidazole (MNZ). CAM resistance was most frequent, occurring in 43.4% of patients; that of MNZ was 21.9%. Adverse events were observed in 13.8% of cases. In total, 587 cases of H. pylori infection were analyzed and no serious adverse events were observed. CONCLUSIONS: Treatment for H. pylori in children and adolescents is safe, but further studies on treatment regimens should be conducted to improve eradication rates and monitor increasing CAM resistance.

Comparison of Iron-Binding Ability Between Thr70-NapA and Ser70-NapA of Helicobacter pylori.

BACKGROUND: The neutrophil-activating protein (NapA) of Helicobacter pylori (H. pylori), with DNA-binding and iron seizing properties, is a fundamental virulence factor involved in H. pylori-related diseases. Compared with Ser70-NapA strain, Thr70-NapA strain is more intimately correlated with iron-deficiency anemia. METHODS: To investigate whether two types of proteins differ in iron-binding ability, mutated Thr70-NapA and Ser70-NapA strains were established. Isothermal titration calorimetry (ITC) method was conducted to measure the binding between the NapA protein and Fe(2+) . The structural changes of NapA protein were also tested during iron interaction by fast protein liquid chromatography (FPLC) and circular dichroism (CD) methods. DNA-binding assay was performed for evaluate the affinity of both mutated and wild types of NapA with DNA. RESULTS: Mutated Thr70-NapA had higher iron-binding ability than wild Ser70-NapA. The structural stability of Thr70-NapA was disrupted and became more active along with the rising concentration of Fe(2+) , whereas no similar association was observed between Ser70-NapA and Fe(2+) level. When the iron/protein molar ratio ranged from 10 to 20, both Ser70-NapA and Thr70-NapA displayed weaker DNA-binding ability. CONCLUSIONS: Thr70-NapA has much stronger ability to sequester ferrous ion compared with Ser70-NapA in H. pylori. In addition, the DNA-binding property of NapA is dependent upon the Fe(2+) concentration.

Effect of Vitamin E With Therapeutic Iron Supplementation on Iron Repletion and Gut Microbiome in US Iron Deficient Infants and Toddlers.

BACKGROUND: Iron therapy induces inflammation, which could decrease iron absorption. Increased exposure of iron in the gut could also alter microbiome file. Providing antioxidants such as vitamin E with iron therapy has been associated with reduced oxidative potential. OBJECTIVE: The aim of the present study was to test the efficacy of adding vitamin E to therapeutic iron therapy on iron repletion, inflammation markers, and gut microbiome in iron-deficient infants and toddlers. DESIGN: This was a randomized, double-blind, control trial in which infants and toddlers (Denver, CO metro area) who were at risk of iron deficiency were screened. Eligible participants were randomized to receive iron therapy (6 mg ·â€Škg ·â€Šday) plus placebo (n = 22) or iron (6 mg ·â€Škg ·â€Šday) and vitamin E (18 mg/day, n = 14) for 8 weeks. Iron and inflammation status, and gut microbiome (16S sequencing) were analyzed in all participants before and after the treatment. RESULTS: After 8 weeks of treatment, average serum ferritin level returned to normal for both iron + placebo and iron + vitamin E groups at 33.3 ±â€Š20.2 and 33.5 ±â€Š21.5 µg/L, respectively. Serum vitamin E concentration increased in iron + vitamin E group. No change over time was observed regarding serum interleukin-4, tumor necrosis factor-α, or fecal calprotectin. The relative abundance of the genus Roseburia (phylum Firmicutes), a butyrate producer, increased in the Fe + E group (Δ1.3%, P < 0.01). Also at the genus level, the genus Escherichia decreased by 1.2% on average among all participants (effect of time P = 0.01). CONCLUSIONS: Using a therapeutic iron dose of 6 mg ·â€Škg ·â€Šday is effective in treating iron deficiency during an 8-week period, without inducing persistent inflammatory response. Changes of the gut microbiome raised the possibility that antioxidant therapy in conjunction with therapeutic iron supplementation could potentially improve microbial community profiles in the intestinal tract.

[The increasing and expression of virulence factors of opportunistic microorganisms in blood serum under various alternatives of iron homeostasis].

Staphylococcus aureus and Pseudomonas aeruginosa are foregroundpathogens of bacteriemia and sepsis. They produce large spectrum of such factors of pathogenicity permitting them to proliferate and survive in bloodstream as hydrolytic enzymes, adenosine diphosphate-ribosylarginine toxins, plasmocoagulase, etc. The occurrence of alteration of growth and expression of virulence factors of S. aureus and P. aeruginosa at fermentation in LB-broth depending on iron concentration was demonstrated previously. The conditions in vivo significantly differ the laboratory conditions. The activity of growth and expression of pathogenicity factors of S. aureus and P. aeruginosa at fermentation in blood serum of donors with different alternative of iron homeostasis was analyzed. The study established expression of genes of hemolytic phospholipase C (plcH), alginate (algD), exotoxin A (exoA) for P. aeruginosa and genes of protein A (spA), virulence global regulator (RNAIII) for S. aureus. The iron-deficient serum and serum with normal iron homeostasis decreased activity of growth of S. aureus and P. aeruginosa. The growth rate and expression level of all analyzed genes turned out higher at fermentation of S. aureus and P. aeruginosa in serums containing excess of iron (more than 30 mkM). The fermentation of P. aeruginosa in iron-deficient serum resulted in decreasing of expression level of genes plcH, algD, exoA. The expression of RNA III and spaA S.aureus in iron-deficient serum increased towards normal content of iron in blood. The example of S. aureus and P. aeruginosa demonstrated that expression of many virulence factors of opportunistic microorganisms depends on iron homeostasis of host organism. The survival and proliferation of microorganisms in blood depend on both immune status of host organism and biological characteristics of pathogen.

Mutagenicity and clastogenicity of extracts of Helicobacter pylori detected by the Ames test and in the micronucleus test using human lymphoblastoid cells.

Epidemiological studies have demonstrated a close association between infection with Helicobacter pylori (H.pylori) and the development of gastric carcinoma. Chronic H.pylori infection increases the frequency of mutation in gastric epithelial cells. However, the mechanism by which infection of H.pylori leads to mutation in gastric epithelial cells is unclear. We suspected that components in H.pylori may be related to the mutagenic response associated with DNA alkylation, and could be detected with the Ames test using a more sensitive strain for alkylating agents. Our investigation revealed that an extract of H.pylori was mutagenic in the Ames test with Salmonella typhimurium YG7108, which is deficient in the DNA repair of O(6)-methylguanine. The extract of H.pylori may contain methylating or alkylating agents, which might induce O (6)-alkylguanine in DNA. Mutagenicity of the alkylating agents N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine in the Ames test with S.typhimurium TA1535 was enhanced significantly in the presence of the extract of H.pylori. The tested extracts of H.pylori resulted in a significant induction of micronuclei in human-derived lymphoblastoid cells. Heat instability and dialysis resistance of the extracts of H.pylori suggest that the mutagenic component in the extracts of H.pylori is a heat-unstable large molecule or a heat-labile small molecule strongly attached or adsorbed to a large molecule. Proteins in the extracts of H.pylori were subsequently fractionated using ammonium sulphate precipitation. However, all fractions expressed enhancing effects toward MNU mutagenicity. These results suggest the mutagenic component is a small molecule that is absorbed into proteins in the extract of H.pylori, which resist dialysis. Continuous and chronic exposure of gastric epithelial cells to the alkylative mutagenic component from H.pylori chronically infected in the stomach might be a causal factor in the gastric carcinogenesis associated with H.pylori.

Effects of iron supplementation on dominant bacterial groups in the gut, faecal SCFA and gut inflammation: a randomised, placebo-controlled intervention trial in South African children.

Fe supplementation is a common strategy to correct Fe-deficiency anaemia in children; however, it may modify the gut microbiota and increase the risk for enteropathogenic infection. In the present study, we studied the impact of Fe supplementation on the abundance of dominant bacterial groups in the gut, faecal SCFA concentration and gut inflammation in children living in rural South Africa. In a randomised, placebo-controlled intervention trial of 38 weeks, 6- to 11-year-old children with Fe deficiency received orally either tablets containing 50 mg Fe as FeSO4 (n 22) for 4 d/week or identical placebo (n 27). In addition, Fe-sufficient children (n 24) were included as a non-treated reference group. Faecal samples were analysed at baseline and at 2, 12 and 38 weeks to determine the effects of Fe supplementation on ten bacterial groups in the gut (quantitative PCR), faecal SCFA concentration (HPLC) and gut inflammation (faecal calprotectin concentration). At baseline, concentrations of bacterial groups in the gut, faecal SCFA and faecal calprotectin did not differ between Fe-deficient and Fe-sufficient children. Fe supplementation significantly improved Fe status in Fe-deficient children and did not significantly increase faecal calprotectin concentration. Moreover, no significant effect of Fe treatment or time × treatment interaction on the concentrations of bacterial groups in the gut or faecal SCFA was observed compared with the placebo treatment. Also, there were no significant differences observed in the concentrations of any of the bacterial target groups or faecal SCFA at 2, 12 or 38 weeks between the three groups of children when correcting for baseline values. The present study suggests that in African children with a low enteropathogen burden, Fe status and dietary Fe supplementation did not significantly affect the dominant bacterial groups in the gut, faecal SCFA concentration or gut inflammation.

Serum hepcidin levels in Helicobacter pylori-infected children with iron-deficiency anemia: a case-control study.

Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of systemic iron homeostasis. Hepcidin integrates signals from diverse physiological inputs, forming a key connection between iron trafficking and response to infection. In this study, we aimed to investigate whether Helicobacter pylori infection modulates serum hepcidin level and response to oral iron therapy in children with iron-deficiency anemia. This was a case-control study including 60 children with iron-deficiency anemia (IDA; 30 H. pylori infected and 30 H. pylori noninfected) and 30 healthy children with comparable age and gender as the control group. Iron parameters including serum iron, ferritin, transferrin, total iron binding capacity, and transferrin saturation and serum hepcidin levels were assessed initially and after 3 months of oral iron therapy for IDA. Compared to the control group, serum hepcidin was significantly lower in H. pylori-noninfected children with IDA (P < 0.01) and significantly higher in H. pylori-infected children with IDA (P < 0.01). Hepcidin increased significantly in noninfected children with IDA after 3 months of oral iron therapy (P < 0.01). On the other hand, H. pylori-infected children showed nonsignificant change in hepcidin level after oral iron therapy (P > 0.05). Although hepcidin showed significant positive correlations with serum ferritin, hemoglobin (Hb), iron, and transferrin saturation in noninfected children with IDA (P < 0.01), it showed significant negative correlations with serum ferritin, Hb, iron, and transferrin saturation in H. pylori-infected children with IDA (P < 0.05). H. pylori infection upregulates serum hepcidin levels and was associated with diminished response to oral iron therapy in children with iron-deficiency anemia.

Iron deficiency anemia due to lymphocytic gastritis with Helicobacter pylori infection in childhood: case report.

Lymphocytic gastritis (LG) is a chronic inflammatory process of poorly understood pathogenesis. We report the case of a 12-year-old premenstrual girl with refractory iron deficiency anemia in which the oral iron absorption challenge suggested iron malabsorption. Laboratory studies ruled out celiac disease and autoimmune gastritis, and carbon-13 urea breath test for Helicobacter pylori was also negative. Upper endoscopy with gastric body and antral mucosa biopsies revealed a LG with focal intestinal metaplasia and H. pylori infection. H. pylori eradication was undertaken with success and 3 months later her hematologic parameters normalized. Histologic reevaluation showed disappearance of LG. This case shows that investigation of malabsorption disease in the presence of refractory iron deficiency anemia can lead to the diagnosis of important gastric diseases, even in the absence of gastrointestinal symptoms. This nonceliac child was diagnosed with a severe histopathologic pattern of LG, with potential risk of malignant transformation, which was completely reverted with adequate H. pylori eradication treatment.

The role of prohepcidin in anemia due to Helicobacter pylori infection.

BACKGROUND: Hepcidin, a key regulator of iron homeostasis, increases when inflammation and some infections occur. It plays a critical role in macrophage iron retention, which underlies inflammation/infection caused anemia. It is known that Helicobacter pylori (HP) may lead to iron deficiency (ID) due to occult blood loss or reduced iron absorption. This study investigates the role of prohepcidin, hepcidin's precursor, in ID and ID anemia (IDA) with a concurrent HP infection. METHODS: In this prospectively designed study, 15 patients with IDA and a concurrent HP infection (group 1), 11 patients with an ID and a concurrent HP infection (group 2), and 18 patients with HP infection (group 3) were observed. All groups received only HP eradication therapy. Twenty-five age- and sex-matched children without ID/IDA and HP infection were included in the study as the control group. In all groups and control group, measurements were taken for pre- and posttreatment hemoglobin, serum prohepcidin, serum ferritin, serum iron (SI), transferrin saturation, erythrocyte sedimentation rate, fibrinogen, and C-reactive protein levels. RESULTS: The pretreatment prohepcidin levels were significantly higher only in group 1 compared to the control group (P < .05). In group 1, a significant increase in hemoglobin and SI levels and a significant reduction in prohepcidin levels were additionally observed following HP eradication treatment (P < .05). However, in groups 2 and 3, significant differences in hemoglobin, iron, and prohepcidin levels between pre- and posttreatment were not observed. CONCLUSION: Elevated serum prohepcidin might indicate the role of inflammation in the etiology of anemia concurrent with HP.

[Kirlianography used to treat patients who are suffering from iron-deficiency anemia with gastroenterological pathology].

The data given below show the efficiency of the therapy of the patients suffering from iron-deficiency anemia with gastroenterological pathology and helicobacter infection. The indicators of red blood of the patients from the group where they had been treated with medicine containing iron and antihelicobacterial therapy had a tendency to be higher with a prolonged compensation of anemia in comparison with the group of the patients who had not had antibacterial therapy. Finger kirliandiagnostics was offered as an express-method to identify a possible infection. The feature of a high probability of infection is intoxication in gastroduodenal zone, abdomen area and a colon.

[The role of Helicobacter pylori infection in hematological diseases - a review].

Helicobacter pylori (H. pylori) infection has been known to be the most closely associated with extra-gastrointestinal diseases. Above all, the association between H. pylori and hematological diseases, including immune thrombocytopenic purpura ( ITP), gastric MALT lymphoma and iron deficiency anemia (IDA) has been focused. Although the molecular mechanisms have not yet been fully understood, H. pylori eradication resulted in high response rates without major adverse effects. We focus here on a comprehensive review of the current literature of ITP, gastric MALT lymphoma and IDA.

Multi-Nutrient Fortified Dairy-Based Drink Reduces Anaemia without Observed Adverse Effects on Gut Microbiota in Anaemic Malnourished Nigerian Toddlers: A Randomised Dose-Response Study.

Prevalence of anaemia among Nigerian toddlers is reported to be high, and may cause significant morbidity, affects brain development and function, and results in weakness and fatigue. Although, iron fortification can reduce anaemia, yet the effect on gut microbiota is unclear. This open-label randomised study in anaemic malnourished Nigerian toddlers aimed to decrease anaemia without affecting pathogenic gut bacteria using a multi-nutrient fortified dairy-based drink. The test product was provided daily in different amounts (200, 400 or 600 mL, supplying 2.24, 4.48 and 6.72 mg of elemental iron, respectively) for 6 months. Haemoglobin, ferritin, and C-reactive protein concentrations were measured to determine anaemia, iron deficiency (ID) and iron deficiency anaemia (IDA) prevalence. Faecal samples were collected to analyse gut microbiota composition. All three dosages reduced anaemia prevalence, to 47%, 27% and 18%, respectively. ID and IDA prevalence was low and did not significantly decrease over time. Regarding gut microbiota, Enterobacteriaceae decreased over time without differences between groups, whereas Bifidobacteriaceae and pathogenic E. coli were not affected. In conclusion, the multi-nutrient fortified dairy-based drink reduced anaemia in a dose-dependent way, without stimulating intestinal potential pathogenic bacteria, and thus appears to be safe and effective in treating anaemia in Nigerian toddlers.

Risk of Infection Associated With Administration of Intravenous Iron: A Systematic Review and Meta-analysis.

Importance: Intravenous iron is recommended by many clinical guidelines based largely on its effectiveness in reducing anemia. However, the association with important safety outcomes, such as infection, remains uncertain. Objective: To examine the risk of infection associated with intravenous iron compared with oral iron or no iron. Data Sources: Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials (RCTs) from 1966 to January 31, 2021. Ongoing trials were sought from ClinicalTrials.gov, CENTRAL, and the World Health Organization International Clinical Trials Search Registry Platform. Study Selection: Pairs of reviewers identified RCTs that compared intravenous iron with oral iron or no iron across all patient populations, excluding healthy volunteers. Nonrandomized studies published since January 1, 2007, were also included. A total of 312 full-text articles were assessed for eligibility. Data Extraction and Synthesis: Data extraction and risk of bias assessments were performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) and Cochrane recommendations, and the quality of evidence was assessed using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Two reviewers extracted data independently. A random-effects model was used to synthesize data from RCTs. A narrative synthesis was performed to characterize the reporting of infection. Main Outcomes and Measures: The primary outcome was risk of infection. Secondary outcomes included mortality, hospital length of stay, and changes in hemoglobin and red blood cell transfusion requirements. Measures of association were reported as risk ratios (RRs) or mean differences. Results: A total of 154 RCTs (32 920 participants) were included in the main analysis. Intravenous iron was associated with an increased risk of infection when compared with oral iron or no iron (RR, 1.17; 95% CI, 1.04-1.31; I2 = 37%; moderate certainty of evidence). Intravenous iron also was associated with an increase in hemoglobin (mean difference, 0.57 g/dL; 95% CI, 0.50-0.64 g/dL; I2 = 94%) and a reduction in the risk of requiring a red blood cell transfusion (RR, 0.93; 95% CI, 0.76-0.89; I2 = 15%) when compared with oral iron or no iron. There was no evidence of an effect on mortality or hospital length of stay. Conclusions and Relevance: In this large systematic review and meta-analysis, intravenous iron was associated with an increased risk of infection. Well-designed studies, using standardized definitions of infection, are required to understand the balance between this risk and the potential benefits.

Gut Microbial and Metabolic Profiling Reveal the Lingering Effects of Infantile Iron Deficiency Unless Treated with Iron.

SCOPE: Iron deficiency (ID) compromises the health of infants worldwide. Although readily treated with iron, concerns remain about the persistence of some effects. Metabolic and gut microbial consequences of infantile ID were investigated in juvenile monkeys after natural recovery (pID) from iron deficiency or post-treatment with iron dextran and B vitamins (pID+Fe). METHODS AND RESULTS: Metabolomic profiling of urine and plasma is conducted with 1 H nuclear magnetic resonance (NMR) spectroscopy. Gut microbiota are characterized from rectal swabs by amplicon sequencing of the 16S rRNA gene. Urinary metabolic profiles of pID monkeys significantly differed from pID+Fe and continuously iron-sufficient controls (IS) with higher maltose and lower amounts of microbial-derived metabolites. Persistent differences in energy metabolism are apparent from the plasma metabolic phenotypes with greater reliance on anaerobic glycolysis in pID monkeys. Microbial profiling indicated higher abundances of Methanobrevibacter, Lachnobacterium, and Ruminococcus in pID monkeys and any history of ID resulted in a lower Prevotella abundance compared to the IS controls. CONCLUSIONS: Lingering metabolic and microbial effects are found after natural recovery from ID. These long-term biochemical derangements are not present in the pID+Fe animals emphasizing the importance of the early detection and treatment of early-life ID to ameliorate its chronic metabolic effects.

Relationship between duodenal microbiota composition, clinical features at diagnosis, and persistent symptoms in adult Coeliac disease.

BACKGROUND: Duodenal dysbiosis has been suggested to possibly influence the clinical manifestations of coeliac disease (CD), both at onset and when symptoms persist despite a gluten-free diet (GFD). AIMS: To evaluate the relationship between duodenal microbiota composition and: i) clinical phenotype of untreated CD (UCD); ii) presence and type of persistent symptoms despite a satisfactory serological and histological response to a strict GFD. METHODS: Duodenal microbiota was analyzed by 16S rRNA sequencing and compared with i) clinical features in 12 adult UCD patients; ii) presence/absence and type of persistent symptoms (diarrhea-predominant vs. non-diarrhea predominant) in 25 adult treated coeliac patients (TCD) on a strict GFD. RESULTS: UCD with iron deficiency anemia (IDA) had a pro-inflammatory shift in their duodenal microbiota (reduction of Firmicutes, p = 0.03; increase of beta-Proteobacteria, p = 0.02) than those without IDA. TCD with persistent diarrhea showed a reduction of Actinobacteria (p = 0.03) and Rothia spp (p = 0.046) compared to TCD suffering from other type of persistent symptoms. CONCLUSION: A distinctive duodenal microbiota profile is associated with IDA in UCD, and diarrhea-predominant persistent symptoms in TCD. Clinical interventions may include reconsidering patients presenting with IDA as a specific disease subtype, and dietary rebalancing if diarrhea persists despite histological response to a GFD.

Helicobacter pylori infection and current clinical areas of contention.

PURPOSE OF REVIEW: The indication for Helicobacter pylori (H. pylori) eradication has been extended to few extragastroduodenal diseases. Scientific rigor needs to be applied as the list of clinical manifestations potentially related to H. pylori has disproportionally grown to its scientific evidence. Some potential beneficial aspects of H. pylori in allergic diseases and in the context of obesity are critically addressed in this review. The main challenge, however, continues to be the prevention of gastric cancer by H. pylori eradication. Strategies for identification of individuals and populations at risk are reported as well. A final aspect is dedicated to novel treatment regimens for overcoming the increasing treatment failures with proton pump inhibitor-based triple standards. RECENT FINDINGS: H. pylori infection is associated with some extragastric diseases such as idiopathic thrombocytic purpura and iron deficiency anemia that benefit from eradication therapy. The inverse relation of H. pylori prevalence and the increase in allergies and obesity, as reported from epidemiological studies, has prompted research for elucidating potential underlying pathophysiological mechanisms. Strategies for gastric cancer prevention include serological screening, which allow adopting eradication therapy in individuals at high risk. New treatments for H. pylori include sequential, bismuth-based quadruple and nonbismuth-based quadruple therapies. SUMMARY: The main clinical challenge remains prevention of H. pylori-related diseases by effective treatment and screening procedures.

Low levels of faecal lactobacilli in women with iron-deficiency anaemia in south India.

Fe deficiency in women contributes significantly to maternal and child morbidity in India. The intestinal bacterial flora may facilitate absorption of Fe from the caecum and proximal colon. The present study investigated the possibility that intestinal microbiota of anaemic young women may differ from that of women with normal Hb levels. The microbiota was quantified by real-time PCR in faeces of eight anaemic (Hb ≤ 100 g/l) and twenty-six normohaemic (Hb ≥ 120 g/l) women aged 18-25 years. Sequences of 16S ribosomal DNA (rDNA) specific to Bifidobacterium genus, Lactobacillus acidophilus group, Bacteroides-Prevotella-Porphyromonas group, Clostridium leptum group and Eubacterium rectale were amplified and expressed (as relative difference) relative to the universally conserved bacterial 16S rDNA sequences. Dietary intakes of energy, carbohydrate, fibre and Fe were ascertained by maintenance of a diet diary for a week. Faecal lactobacilli were significantly lower in anaemic women (median 6.6 × 10(-8), relative difference compared with total bacteria) than in the reference group (2.9 × 10(-6); P = 0.001, unpaired t test with logarithmic transformation). There was no difference between the two groups with respect to any of the other bacteria that were examined. Intakes of energy, carbohydrate, fibre, Fe and milk were similar in both the groups. Fe deficiency in young women in south India was associated with low levels of lactobacilli in the faeces. The relationship between lactobacilli and Fe deficiency needs to be explored further.