SP134GUT - KIDNEY AXIS IN THE PATHOGENESIS OF IGA NEPHROPATHY

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Effect of whole-grain barley on the human fecal microbiota and metabolome

In this study, we compared the fecal microbiota and metabolomes of 26 healthy subjects before (HS) and after (HSB) 2 months of diet intervention based on the administration of durum wheat flour and whole-grain barley pasta containing the minimum recommended daily intake (3 g) of barley β-glucans. Metabolically active bacteria were analyzed through pyrosequencing of the 16S rRNA gene and community-level catabolic profiles. Pyrosequencing data showed that levels of Clostridiaceae (Clostridium orbiscindens and Clostridium sp.), Roseburia hominis, and Ruminococcus sp. increased, while levels of other Firmicutes and Fusobacteria decreased, from the HSB samples to the HS fecal samples. Community-level catabolic profiles were lower in HSB samples. Compared to the results for HS samples, cultivable lactobacilli increased in HSB fecal samples, while the numbers of Enterobacteriaceae, total coliforms, and Bacteroides, Porphyromonas, Prevotella, Pseudomonas, Alcaligenes, and Aeromonas bacteria decreased. Metabolome analyses were performed using an amino acid analyzer and gas chromatography-mass spectrometry solid-phase microextraction. A marked increase in short-chain fatty acids (SCFA), such as 2-methyl-propanoic, acetic, butyric, and propionic acids, was found in HSB samples with respect to the HS fecal samples. Durum wheat flour and whole-grain barley pasta containing 3% barley β-glucans appeared to be effective in modulating the composition and metabolic pathways of the intestinal microbiota, leading to an increased level of SCFA in the HSB samples

Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN).

This study aimed at investigating the fecal microbiota, and the fecal and urinary metabolome of non progressor (NP) and progressor (P) patients with immunoglobulin A nephropathy (IgAN). Three groups of volunteers were included in the study: (i) sixteen IgAN NP patients; (ii) sixteen IgAN P patients; and (iii) sixteen healthy control (HC) subjects, without known diseases. Selective media were used to determine the main cultivable bacterial groups. Bacterial tag-encoded FLX-titanium amplicon pyrosequencing of the 16S rDNA and 16S rRNA was carried out to determine total and metabolically active bacteria, respectively. Biochrom 30 series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase microextraction (GC-MS/SPME) analyses were mainly carried out for metabolomic analyses. As estimated by rarefaction, Chao and Shannon diversity index, the lowest microbial diversity was found in P patients. Firmicutes increased in the fecal samples of NP and, especially, P patients due to the higher percentages of some genera/species of Ruminococcaceae, Lachnospiraceae, Eubacteriaceae and Streptococcaeae. With a few exceptions, species of Clostridium, Enterococcus and Lactobacillus genera were found at the highest levels in HC. Bacteroidaceae, Porphyromonadaceae, Prevotellaceae and Rikenellaceae families differed among NP, P and HC subjects. Sutterellaceae and Enterobacteriaceae species were almost the highest in the fecal samples of NP and/or P patients. Compared to HC subjects, Bifidobacterium species decreased in the fecal samples of NP and P. As shown by multivariate statistical analyses, the levels of metabolites (free amino acids and organic volatile compounds) from fecal and urinary samples markedly differentiated NP and, especially, P patients

A LOW-SODIUM BREAD IMPROVES THE ADHERENCE TO A LOW-SODIUM DIET IN HYPERTENSIVE SUBJECTS

INTRODUCTION AND AIMS: Salt intake is a critical factor in hypertension and compliance to low-sodium diets is often scarce in these patients. In this context, a significant reduction in the hidden salt of processed foods might represent an effective strategy to achieve the target sodium intake. The aim of the study was to verify the hypothesis that the use of a low-sodium functional bread, in the context of a lowsodium diet, could increase the adherence to the latter and help to achieve blood pressure (BP) reduction. METHODS: We carried on a 6-months multi-center randomized controlled trial on hypertensive patients. Fifty-four subjects suffering from stadium I-II hypertension were enrolled and randomized in 3 study arms. Group A (n=19) followed a free diet with the use of standard Altamura bread (750 mg Na/100g), group B (n=17) followed a low-sodium (2300 mg Na/die) diet including the use of standard Altamura bread, while group C (n=18) followed a low-sodium (2300 mg Na/die) diet including the use of innovative, low-sodium “PANdelCUORE” Altamura bread (280 mg Na/100g). We measured blood pressure, serum and urine sodium concentration, and endothelial function by flow-mediated dilation (FMD). Results were expressed as mean 6 SD or median and interquartile ranges. Continuous variables were analyzed by paired tStudent test or by Wilcoxon test, as opportune. P-values < 0.05 were considered statistically significant. RESULTS: After 6 months, urinary sodium (113.0 [102.5-157.5] vs 155 [150.5-231.5] mEq/24h, p=0.02), systolic (131.6769.08 vs 139.28610.26 mmHg, p=0.01) and diastolic (81.9467.89 vs 88.8965.67 mmHg, p=0.002) BP were significantly reduced as compared to baseline levels only in group C. Urinary sodium: group A 140.5 [84.0- 178.0] vs 162.5 [129.3-198.0] mEq/24h, p=0.11; group B 145.0 [124.5-193.5] vs 148.0 [108.0-269.0] mEq/24h, p=0.59. Systolic BP: group A 135.53614.62 vs 138.42610.42 mmHg, p=0.28; group B 132.06612.51 vs 134.5969.77 mmHg, p=0.51. Diastolic BP: group A 83.6869.55 vs 85.4266.79, p=0.37; group B 85.59610.29 vs 84.1265.66 mmHg, p=0.62. FMD improved in all the three groups, although more remarkably in group C (group A: 9.7262.50 vs 7.4361.40%, p=0.02; group B: 10.3562.65 vs 5.8162.03%, p=0.02; 10.8462.68 vs 5.5761.98%, p=0.0004). FMD did not show any significant correlation with BP. CONCLUSIONS: This is, in our knowledge, the first study exploring the differential adherence to a dietary salt restriction by comparing the use of a low-sodium functional food vs a conventional one. We demonstrate here that the use of a low-sodium bread increases the adherence to a low-sodium diet and that their association is effective to significantly decrease sodium excretion and BP. Group B patients, although theoretically following a diet providing the same sodium intake of group C, failed to achieve sodium excretion and BP reduction. Moreover, we obtained a BP-independent effect on FMD in all the enrolled patients, suggesting that even small reductions in sodium intake could result in amelioration of endothelial reactivity. Our data encourage the strategy of salt reduction in processed foods as effective for BP decrease in hypertensive patients

Beta-Glucans Supplementation Associates with Reduction in P-Cresyl Sulfate Levels and Improved Endothelial Vascular Reactivity in Healthy Individuals.

Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD).The aim of our study was to evaluate whether a nutritional intervention with a functional pasta enriched with beta-glucans could promote a saccharolytic shift on the gut microbial metabolism and improve FMD.We carried out a pilot study on 26 healthy volunteers who underwent a 2-month dietary treatment including a daily administration of Granoro "Cuore Mio" pasta enriched with barley beta-glucans (3g/100g). Blood and urine routine parameters, serum pCS/IS and FMD were evaluated before and after the dietary treatment.The nutritional treatment significantly reduced LDL and total cholesterol, as expected. Moreover, following beta-glucans supplementation we observed a reduction of serum pCS levels and an increase of FMD, while IS serum levels remained unchanged.We demonstrated that a beta-glucans dietary intervention in healthy volunteers correlates with a saccharolytic shift on the gut microbiota metabolism, as suggested by the decrease of pCS and the increase of SCFA, and associates with an improved endothelial reactivity. Our pilot study suggests, in addition to cholesterol, novel pCS-lowering properties of beta-glucans, worthy to be confirmed in large-scale trials and particularly in contexts where the reduction of the microbial-derived uremic toxin pCS is of critical importance, such as in chronic kidney disease

Effects of low-sodium bread on dietary compliance and fecal cultivable bacteria in a randomized controlled pilot trial in hypertensive subjects

High salt intake and compliance to low-sodium (LS) diets are critical in hypertension. Salt reduction in processed foods can help to achieve the target sodium intake. To verify the hypothesis that an innovative LS formulation of a traditional bread could result in a reduction of sodium intake and blood pressure, we performed a 6-month randomized controlled pilot trial on hypertensive patients. We additionally explored the effects of sodium restriction on blood pressure and fecal cultivable bacteria.Fifty-seven patients were randomized in three groups. Group A (n = 19) followed a free diet using standard bread (750 mg Na/100 g), group B (n = 18) followed a LS diet (2300 mg Na/die) using standard bread, group C (n = 20) followed a LS diet (2300 mg Na/die) using LS bread (280 mg Na/100 g). We measured 24-h urinary sodium, blood pressure, routine parameters, fecal microbial counts (26 patients).After 6 months, as compared to group A, group C showed a reduction of 24-h urinary sodium excretion (-908 mg/24 h), diastolic pressure (-9 mmHg) and microbial counts of Bacteroides, Porphyromonas, Prevotella, Enterobacteriaceae, Staphylococcus, Micrococcus. These results suggest that LS bread could increase the adherence to a LS diet, reducing sodium excretion, diastolic pressure and abundance of some fecal cultivable bacteria.Trial registration Registration nr. NCT03127553, on 25/04/2017

An Innovative Synbiotic Formulation Decreases Free Serum Indoxyl Sulfate, Small Intestine Permeability and Ameliorates Gastrointestinal Symptoms in a Randomized Pilot Trial in Stage IIIb-IV CKD Patients

Proteolytic dysbiosis of the gut microbiota has been recognized as both a typical feature of chronic kidney disease (CKD) and a risk factor for its progression. Blood accumulation of gut-derived uremic toxins (UTs) like indoxyl sulfate (IS) and p-cresyl sulfate (PCS), intestinal permeability and constipation are typical features accompanying CKD progression and triggering chronic inflammation. In order to verify the efficacy of the innovative synbiotic formulation NATUREN G® in modulating the levels of circulating UTs, intestinal permeability and gastrointestinal symptoms, we set up a randomized, single-blind, placebo-controlled, pilot trial in stage IIIb-IV CKD patients and in healthy controls. Two-month administration of the synbiotic resulted in a decrease of free IS, as compared with the placebo-treated arm, only in the CKD group. The other UTs did not significantly change, although different trends in time (increase in the placebo arm and decrease in the synbiotic arm) were observed. Moreover, after supplementation, reduction of small intestinal permeability and amelioration of abdominal pain and constipation syndromes were observed only in the CKD group. The obtained results suggest the specificity of action of NATUREN G® in CKD and justify further validation in a wider study population

Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO)

The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy

Total and active bacteria found in feces of subjects.

<p>Relative abundance (%) of total (16S rDNA) and metabolically active (16S rRNA) bacteria, which were found at the phylum level in the fecal samples of immunoglobulin A nephropathy (IgAN) non progressor (NP) and progressor (P) patients, and healthy controls (HC).</p

Principal component analysis (PCA) of volatile organic metabolites found in feces of subjects.

<p>Score plots of the two principal components (PC) after principal component analysis (PCA) of volatile organic metabolites of the fecal (A) and urine (B) samples of immunoglobulin A nephropathy (IgAN) non progressor (NP) and progressor (P) patients, and healthy controls (HC).</p