Association Between Breastfeeding and the Development of Childhood Diabetes Mellitus Type I (DM I): The Effect of Prolonged Exclusive Breastfeeding on Gut Microbiome and the Link with DM I

The role of breastfeeding and dietary habits was studied in 10 children with DM I (case group) and compared with 10 healthy controls. Our results showed that the case group had significantly shorter exclusive breastfeeding duration compared with the control group (p = 0.006). An in silico comparative analysis of gut microbiota data from two recent studies was also performed in order to identify any specific bacterial genera potentially associated with DM I, due to prolonged breastfeeding. The Pasteurellaceae family, found in breast milk, was shown to have a significantly higher population in the intestine in the control group (p = 0.010). Overall, this preliminary study showed that exclusive breastfeeding duration is strongly associated with DM I. An association between breast milk microbiome and gut microbiome was also observed. This should encourage further research, aiming to examine both the effect of breastfeeding on gut microbiome and the possible links with DM I

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

(Poly)phenols are a large group of compounds, found in food, beverages, dietary supplements and herbal medicines. Owing to their biological activities, absorption and metabolism of the most abundant compounds in humans are well understood. Both the chemical structure of the phenolic moiety and any attached chemical groups define whether the polyphenol is absorbed in the small intestine, or reaches the colon and is subject to extensive catabolism by colonic microbiota. Untransformed substrates may be absorbed, appearing in plasma primarily as methylated, sulfated and glucuronidated derivatives, with in some cases the unchanged substrate. Many of the catabolites are well absorbed from the colon and appear in the plasma either similarly conjugated, or as glycine conjugates, or in some cases unchanged. Although many (poly)phenol catabolites have been identified in human plasma and / or urine, the pathways from substrate to final catabolite, and the species of bacteria and enzymes involved, are still scarcely reported. While it is clear that the composition of the human gut microbiota can be modulated in vivo by supplementation with some (poly)phenol-rich commodities, such modulation is definitely not an inevitable consequence of supplementation, it depends on the treatment, length of time and on the individual metabotype, and it is not clear whether the modulation is sustained when supplementation ceases. Some catabolites have been recorded in plasma of volunteers at concentrations similar to those shown to be effective in in vitro studies suggesting that some benefit may be achieved in vivo by diets yielding such catabolites

The role of polyphenols in modern nutrition

Polyphenols are found in plant-based foods and beverages, notably apples, berries, citrus fruit, plums, broccoli, cocoa, tea and coffee, and many others. There is substantial epidemiological evidence that a diet high in polyphenol-rich fruit, vegetables, cocoa and beverages protects against developing cardiovascular disease and type 2 diabetes. The absorption and metabolism of these compounds has been well described and, for many, the gut microbiota play a critical role in absorption; taking into consideration the parent compound and the metabolites from colon bacteria catabolism, more than 80% of a dose can be absorbed and ultimately excreted in the urine. Common polyphenols in the diet are flavanols (cocoa, tea, apples, broad beans), flavanones (hesperidin in citrus fruit), hydroxycinnamates (coffee, many fruits), flavonols (quercetin in onions, apples and tea) and anthocyanins (berries). Many intervention studies, mechanistic in vitro data and epidemiological studies support a role for polyphenols against the development of chronic diseases. For example, flavanols decrease endothelial dysfunction, lower blood pressure and cholesterol, and modulate energy metabolism. Coffee and tea both reduce the risk of developing type 2 diabetes, through action of their constituent polyphenols. Despite extensive research, the exact mechanisms of action of polyphenols in the human body have not been decisively proven, but there is strong evidence that some targets such as nitric oxide metabolism, carbohydrate digestion, and oxidative enzymes are important for health benefits. Consumption of polyphenols as healthy dietary components is consistent with the advice to eat five or more portions of fruit and vegetables per day, but it is currently difficult to recommend what ‘doses’ of specific polyphenols should be consumed to derive maximum benefit

In vitro and in vivo metabolic studies of dietary flavan-3-ols

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Μεταβολικές μελέτες in vitro και in vivo των διατροφικών φλαβαν-3-ολών

Τhe gut microflora metabolism of selected dietary flavan-3-ols was investigated using a static in vitro culture model. Pure procyanidin B2 and its associated monomer, (-)-epicatechin, generated a range of phenolic and phenyl carboxylic acid derivatives. The most abundant were mono- and dihydroxylated phenyl propan-2-ols, mono- and dihydroxylated phenyl valerolactones, a monohydroxylated valeric acid, a monohydroxylated propionic acid and a phenyl acetic acid. Evidence is presented for the production of novel metabolites, from procyanidin B2, that retain the flavanol A-ring and the C4-->C8 interflavan bond, including some of comparatively large mass (Mr ≥ 290) that retain the ‘dimeric’ nature of the substrate. It was confirmed that microbial metabolism favoured dehydroxylation at the position 4’- rather than the 3’-, and that both a- and b-oxidation occurred. The in vitro metabolism of (+)-catechin and (-)-epigallocatechin by human faecal microflora produced fewer metabolites than (-)-epicatechin or procyanidin B2. The in vitro metabolism of crude black tea extracts, theaflavins (TFs) and thearubigins (TRs), did not produce detectable microbial metabolites. Studies using co-cultured cells demonstrated that 3-(3’-hydroxy phenyl) propionic acid was absorbed, similar to, but significantly more slowly (P ≤ 0.05) than ferulic acid. Both compounds were absorbed by passive transcellular transport. The 3-(3’-hydroxy phenyl) propionic acid permeated in its free, unconjugated form, suggesting that is a potentially useful biomarker for examining health promoting effects. Dosing rats intravenously and orally with [14C] procyanidin B2, pharmacokinetic parameters for the [14C] were established. It was demonstrated that a large fraction of the dose of the parent compound administered orally was degraded to different chemical entities by the gut microflora prior to absorption into the systemic circulation.Ο μεταβολισμός της εντερικής μικροχλωρίδας επιλεγμένων διατροφικών φλαβαν-3-ολών ερευνήθηκε χρησιμοποιώντας ένα στατικό μοντέλο καλλιέργειας in vitro. Καθαρή προκυανιδίνη B2 και το σχετιζόμενο μονομερές της, (-)-επικατεχίνη, παρήγαγαν μια σειρά από φαινολικές και φαινυλοκαρβοξυλικές παράγωγες ενώσεις. Οι πιο άφθονες ήταν μονο- και διυδροξυλιωμένες φαινυλοπροπαν-2-όλες, μονο- και διυδροξυλιωμένες φαινυλοβαλερολακτόνες, ένα μονοϋδροξυλιωμένο βαλερικό οξύ, ένα μονοϋδροξυλιωμένο προπιονικό οξύ και ένα φαινυλοξεικό οξύ. Παρουσιάζονται αποδείξεις για την παραγωγή νέων μεταβολιτών από την προκυανιδίνη B2, οι οποίοι διατηρούν τον δακτύλιο A του φλαβανόλης και τον δεσμό C4-->C8 μεταξύ των φλαβανών, συμπεριλαμβανομένων κάποιων με συγκριτικά μεγάλη μάζα (Mr ≥ 290) που διατηρούν τη ‘διμερική’ φύση του υποστρώματος. Επιβεβαιώθηκε ότι ο μικροβιακός μεταβολισμός προτιμούσε την αποϋδροξυλίωση στη θέση 4’- παρά στη 3’-, και και ότι έλαβαν χώρα τόσο α- όσο και β-οξείδωση.Ο μεταβολισμός in vitro της (+)-κατεχίνης και της (-)-επιγαλλοκατεχίνης από την ανθρώπινη εντερική μικροχλωρίδα παρήγαγε λιγότερους μεταβολίτες από ότι η (-)-επικατεχίνη ή η προκυανιδίνη B2. Ο μεταβολισμός in vitro ακατέργαστων εκχυλισμάτων μαύρου τσαγιού, θεαφλαβινών (TFs) και θεαρουβιγινών (TRs), δεν παρήγαγε ανιχνεύσιμους μικροβιακούς μεταβολίτες. Μελέτες χρησιμοποιώντας κυτταρικές καλλιέργειες έδειξαν ότι το 3-(3’-υδροξυφαινυλο) προπιονικό οξύ απορροφήθηκε, παρόμοια με, αλλά σημαντικά πιο αργά (P ≤ 0.05) από το φερουλικό οξύ. Και οι δύο ενώσεις απορροφήθηκαν μέσω παθητικής διακυτταρικής μεταφοράς. Το 3-(3’-υδροξυφαινυλο) προπιονικό οξύ διαπέρασε με την ελεύθερη, μη συζευγμένη μορφή του, υποδεικνύοντας ότι είναι ένας δυνητικά χρήσιμος βιοδείκτης για την εξέταση των ευεργετικών επιδράσεων στην υγεία. Χορηγώντας σε αρουραίους ενδοφλεβίως και από του στόματος [14C] προκυανιδίνη B2, καθορίστηκαν οι φαρμακοκινητικές παράμετροι για το [14C]. Αποδείχθηκε ότι ένα μεγάλο κλάσμα της δόσης της μητρικής ένωσης που χορηγήθηκε από του στόματος, διασπάστηκε σε διάφορες χημικές ενώσεις από την εντερική μικροχλωρίδα πριν από την απορρόφηση στη συστηματική κυκλοφορία