Maternal Diet Shapes the Breast Milk Microbiota Composition and Diversity: Impact of Mode of Delivery and Antibiotic Exposure.

BACKGROUND: Breast milk is a complex biofluid that provides nutrients and bioactive agents, including bacteria, for the development of the infant gut microbiota. However, the impact of maternal diet and other factors, such as mode of delivery and antibiotic exposure, on the breast milk microbiota has yet to be understood. OBJECTIVES: This study aimed to examine the association between maternal diet and breast milk microbiota and to ascertain the potential role of mode of delivery and antibiotic exposure. METHODS: In a cross-sectional study of the MAMI cohort, breast milk microbiota profiling was assessed in 120 samples from healthy mothers by 16S rRNA gene sequencing. Maternal dietary information was recorded through an FFQ, and clinical characteristics, including mode of delivery, antibiotic exposure, and exclusive breastfeeding, were collected. RESULTS: Maternal diet was grouped into 2 clusters: Cluster I (high intake of plant protein, fiber, and carbohydrates), and Cluster II (high intake of animal protein and lipids). Breast milk microbiota was shaped by maternal dietary clusters. Staphylococcus and Bifidobacterium were associated with carbohydrate intake whereas the Streptococcus genus was associated with intakes of the n-3 PUFAs [EPA and docosapentaenoic acid (22:5ω-3)]. Mode of delivery and antibiotic exposure influenced breast milk microbiota in a diet cluster-dependent manner. Differences between/among the maternal dietary clusters were found in the milk microbiota of the cesarean-section (C-section)/antibiotic group, whereas no differences were observed in vaginal births. Lower abundances of Lactobacillus, Bacteroides, and Sediminibacterium genera were observed in Cluster II/C-section/antibiotic exposure compared with the other groups. CONCLUSIONS: Maternal diet shapes the composition and diversity of breast milk microbiota, with the most important contributions coming from dietary fiber and both plant and animal protein intakes. The relation between the maternal diet and the milk microbiota needs further research because it has a key impact on infant microbiota development and contributes to infant health outcomes in the short and long term.This trial was registered at clinicaltrials.gov as NCT03552939.

Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles.

Mothers confer natural passive immunization to their infants through the transplacental pathway during the gestation period. The objective of the present study was to establish at birth the maternal and cord plasma concentration and relationship of immunoglobulins (Igs), cytokines (CKs), and adipokines. In addition, the impact of the maternal microbiota and diet was explored. The plasma profile of these components was different between mothers and babies, with the levels of many CKs, IgM, IgG2a, IgE, IgA, and leptin significantly higher in mothers than in the cord sample. Moreover, the total Igs, all IgG subtypes, IgE, and the Th1/Th2 ratio positively correlated in the mother-infant pair. Maternal dietary components such as monounsaturated fatty acids-polyunsaturated fatty acids and fiber were positively associated with some immune factors such as IgA in cord samples. The microbiota composition clustering also influenced the plasma profile of some factors (i.e., many CKs, some Ig, and adiponectin). In conclusion, we have established the concentration of these immunomodulatory factors in the maternal-neonatal pair at birth, some positive associations, and the influence of maternal diet and the microbiota composition, suggesting that the immune status during pregnancy, in terms of CKs and Igs levels, can influence the immune status of the infant at birth.

The Microbiota and Malnutrition: Impact of Nutritional Status During Early Life.

According to the developmental origins of health and disease hypothesis, our health is determined by events experienced in utero and during early infancy. Indeed, both our prenatal and postnatal nutrition conditions have an impact on the initial architecture and activity of our microbiota. Recent evidence has underlined the importance of the composition of the early gut microbiota in relation to malnutrition, whether it be undernutrition or overnutrition, that is, in terms of both stunted and overweight development. It remains unclear how early microbial contact is linked to the risk of disease, as well as whether alterations in the microbiome underlie the pathogenesis of malnutrition or are merely the end result of it, which indicates that thequestion of causality must urgently be answered. This review provides information on the complex interaction between the microbiota and nutrition during the first 1,000 days of life, taking into account the impact of both undernutrition and overnutrition on the microbiota and on infants' health outcomes in the short- and long-term.

Association of Maternal Secretor Status and Human Milk Oligosaccharides With Milk Microbiota: An Observational Pilot Study.

BACKGROUND AND OBJECTIVES: Breast milk contains several bioactive factors including human milk oligosaccharides (HMOs) and microbes that shape the infant gut microbiota. HMO profile is determined by secretor status; however, their influence on milk microbiota is still uncovered. This study is aimed to determine the impact of the FUT2 genotype on the milk microbiota during the first month of lactation and the association with HMO. METHODS: Milk microbiota from 25 healthy lactating women was determined by quantitative polymerase chain reaction and 16S gene pyrosequencing. Secretor genotype was obtained by polymerase chain reaction-random fragment length polymorphisms and by HMO identification and quantification. RESULTS: The most abundant bacteria were Staphylococcus and Streptococcus, followed by Enterobacteriaceae-related bacteria. The predominant HMO in secretor milk samples were 2'FL and lacto-N-fucopentaose I, whereas non-secretor milk was characterized by lacto-N-fucopentaose II and lacto-N-difucohexaose II. Differences in microbiota composition and quantity were found depending on secretor/non-secretor status. Lactobacillus spp, Enterococcus spp, and Streptococcus spp were lower in non-secretor than in secretor samples. Bifidobacterium genus and species were less prevalent in non-secretor samples. Despite no differences on diversity and richness, non-secretor samples had lower Actinobacteria and higher relative abundance of Enterobacteriaceae, Lactobacillaceae, and Staphylococcaceae. CONCLUSIONS: Maternal secretor status is associated with the human milk microbiota composition and is maintained during the first 4 weeks. Specific associations between milk microbiota, HMO, and secretor status were observed, although the potential biological impact on the neonate remains elusive. Future studies are needed to reveal the early nutrition influence on the reduction of risk of disease.

MAMI: a birth cohort focused on maternal-infant microbiota during early life.

BACKGROUND: Early microbial colonization is a relevant aspect in human health. Altered microbial colonization patterns have been linked to an increased risk of non-communicable diseases (NCDs). Advances in understanding host-microbe interactions highlight the pivotal role of maternal microbiota on infant health programming. This birth cohort is aimed to characterize the maternal microbes transferred to neonates during the first 1000 days of life, as well as to identify the potential host and environmental factors, such as gestational age, mode of delivery, maternal/infant diet, and exposure to antibiotics, which affect early microbial colonization. METHODS: MAMI is a prospective mother-infant birth cohort in the Spanish-Mediterranean area. Mothers were enrolled at the end of pregnancy and families were follow-up during the first years of life. Maternal-infant biological samples were collected at several time points from birth to 24 months of life. Clinical and anthropometric characteristics and dietary information is available. Specific qPCR and 16S rRNA gene sequencing as well as short chain fatty acid (SCFAs) profile would be obtained. Multivariable models will be used to identy associations between microbiota and clinical and anthropometric data controlling for confounders. MAMI would contribute to a better understanding of the interaction between diet, microbiota and host response in early life health programming, enabling new applications in the field of personalized nutrition and medicine. TRIAL REGISTRATION: The study is registered on the ClinicalTrial.gov platform NCT03552939. (June 12, 2018).

Shaping Microbiota During the First 1000 Days of Life.

The data obtained in prior studies suggest that early microbial exposition begins prior to conception and gestation. Given that the host-microbe interaction is shaped by the immune system response, it is important to understand the key immune system-microbiota relationship during the period from conception to the first years of life. The present work summarizes the available evidence concerning early microbiota exposure within the male and the female reproductive tracts at the point of conception and during gestation, focusing on the potential impact on infant development during the first 1000 days of life. Furthermore, we conclude that some dietary strategies including specific probiotics could become potentially valuable tools to modulate the gut microbiota during this early critical window of opportunity for targeted health outcomes throughout the entire lifespan.

Influence of Gestational Age, Secretor, and Lewis Blood Group Status on the Oligosaccharide Content of Human Milk.

OBJECTIVES: Human milk oligosaccharides (HMOs) are considered to play an important role for the infant. As the biotechnical production of some HMOs is feasible today and clinical studies are being designed, the individual variation of the total amount of HMOs and of single components is of particular importance. Our objectives were to investigate whether differences exist between term and preterm milk, milk from mothers with secretor or nonsecretor status, and a Lewis blood group (a+b-), (a-b+), or (a-b-) pattern. METHODS: Within a longitudinal study 96 milk samples (colostrum, transitional, and mature milk) from 32 mothers with preterm (n = 18) and term (n = 14) infants were collected. Delipidated and deproteinized milk was subjected to porous graphitized carbon cartridges followed by high pH anion exchange chromatography with pulsed amperometric detection. RESULTS: Quantitation of 16 single HMOs revealed changes during the first weeks of lactation without discrepancies between term and preterm milk. Significant differences occurred between "secretor" and "nonsecretor" milk (median approximately 10 vs 5 g/L total HMOs). Lacto-N-tetraose (LNT) and lacto-N-fucopentaose (LNFP) II comprised > 55% of the total HMO content in Lewis blood group (a+b-), "nonsecretor" milk and LNT together with 2'fucosyllactose, LNFP I, and difucosyllactose approximately 60% in Lewis (a-b+), "secretor" milk. In Lewis (a-b-), "secretor" milk 80% of oligosaccharides are due to LNT, 2'fucosyllactose, and LNFP I. CONCLUSIONS: There are marked differences in total HMOs and single HMOs in milk depending on Lewis blood group and secretor status, which need to be taken into account in clinical studies.

Breast Milk Polyamines and Microbiota Interactions: Impact of Mode of Delivery and Geographical Location.

BACKGROUND/AIMS: The aim of the present study was to identify and quantify the polyamine levels in human milk obtained from different countries and through different modes of delivery, and to investigate their association with breast milk microbes. METHODS: Mature breast milk samples were obtained from 78 healthy mothers after 1 month of lactation from 4 different geographical locations: Finland, Spain (Europe); South Africa (Africa); and China (Asia). Polyamines were determined using HPLC after dansyl derivatization and milk microbiota was obtained by 16S rRNA gene sequencing. RESULTS: The mean values of polyamines in breast milk were 70.0, 424.2, and 610.0 nmol/dL for putrescine, spermidine and spermine, respectively, and 1,170.9 nmol/dL of total polyamines. The levels of putrescine were significantly higher in Spain (p < 0.05) and spermidine levels were significantly higher in Finland (p < 0.05) compared with other countries. Cesarean delivery had an impact on polyamine levels and it was related to an increase in the putrescine concentration being significant in Spanish samples (p < 0.01). Furthermore, putrescine levels were correlated positively with Gammaproteobacteria (r = 0.46, p < 0.001), especially with Pseudomonas fragi (r = 0.40, p < 0.001). CONCLUSIONS: The results demonstrate significant effect of geographical variations in human milk polyamine concentrations, being correlated with human milk microbiota composition. These differences may have an impact on infant development during lactation.

Reduction of Phytate in Soy Drink by Fermentation with Lactobacillus casei Expressing Phytases From Bifidobacteria.

Plant-based food products can be modified by fermentation to improve flavour and the concentration of some biologically active compounds, but also to increase the mineral availability by eliminating anti-nutrient substances such as phytates. The objective of this study was to develop a fermented soybean drink with improved nutritional quality and source of probiotic bacteria by including as starter for fermentation Lactobacillus casei strains modified to produce phytase enzymes from bifidobacteria. The L. casei strains showed a good adaptation to develop in the soy drink but they needed the addition of external carbohydrates to give rise to an efficient acidification. The strain expressing the Bifidobacterium pseudocatenulatum phytase was able to degrade more than 90 % phytate during product fermentation, whereas expression of Bifidobacterium longum spp. infantis phytase only led to 65 % hydrolysis. In both cases, accumulation of myo-inositol triphosphates was observed. In addition, the hydrolysis of phytate in soy drink fermented with the L. casei strain expressing the B. pseudocatenulatum phytase resulted in phytate/mineral ratios for Fe (0.35) and Zn (2.4), which were below the critical values for reduced mineral bioavailability in humans. This investigation showed the ability of modified L. casei to produce enzymes with technological relevance in the design of new functional foods.

Intake of Natural, Unprocessed Tiger Nuts (Cyperus esculentus L.) Drink Significantly Favors Intestinal Beneficial Bacteria in a Short Period of Time.

Horchata is a natural drink obtained from tiger nut tubers (Cyperus esculentus L.). It has a pleasant milky aspect and nutty flavor; some health benefits have been traditionally attributed to it. This study evaluated the effects of an unprocessed horchata drink on the gut microbiota of healthy adult volunteers (n = 31) who consumed 300 mL of natural, unprocessed horchata with no added sugar daily for 3 days. Although there were no apparent microbial profile changes induced by horchata consumption in the studied population, differences could be determined when volunteers were segmented by microbial clusters. Three distinctive enterogroups were identified previous to consuming horchata, respectively characterized by the relative abundances of Blautia and Lachnospira (B1), Bacteroides (B2) and Ruminococcus and Bifidobacterium (B3). After consuming horchata, samples of all volunteers were grouped into two clusters, one enriched in Akkermansia, Christenellaceae and Clostridiales (A1) and the other with a remarkable presence of Faecalibacterium, Bifidobacterium and Lachnospira (A2). Interestingly, the impact of horchata was dependent on the previous microbiome of each individual, and its effect yielded microbial profiles associated with butyrate production, which are typical of a Mediterranean or vegetable/fiber-rich diet and could be related to the presence of high amylose starch and polyphenols.

Influence of Geographical Location on Maternal-Infant Microbiota: Study in Two Populations From Asia and Europe.

Early gut microbial colonization is driven by many factors, including mode of birth, breastfeeding, and other environmental conditions. Characters of maternal-neonatal microbiota were analyzed from two distinct populations in similar latitude but different continents (Oriental Asia and Europe). A total number of 120 healthy families from China (n=60) and Spain (n=60) were included. Maternal and neonatal microbiota profiles were obtained at birth by 16S rRNA gene profiling. Clinical records were collected. Geographical location influenced maternal-neonatal microbiota. Indeed, neonatal and maternal cores composed by nine genera each one were found independently of location. Geographical location was the most important variable that impact the overall structure of maternal and neoantal microbiota. For neonates, delivery mode effect on neonatal microbial community could modulate how the other perinatal factors, as geographical location or maternal BMI, impact the neoantal initial seeding. Furthermore, lower maternal pre-pregnancy BMI was associated with higher abundance of Faecalibacterium in maternal microbiota and members from Lachnospiraceae family in both mothers and infants. At genus-level, Chinese maternal-neonate dyads possessed higher number of phylogenetic shared microbiota than that of Spanish dyads. Bifidobacterium and Escherichia/Shigella were the genera most shared between dyads in the two groups highlighting their importance in neonatal colonization and mother-infant transmission. Our data showed that early gut microbiota establishment and development is affected by interaction of complex variables, where environment would be a critical factor.

Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health.

Accelerated postnatal growth is a potentially modifiable risk factor for future obesity. To study how specific breast milk components contribute to early growth and obesity risk, we quantified one-carbon metabolism-related metabolites in human breast milk and found an inverse association between milk betaine content and infant growth. This association was replicated in an independent and geographically distinct cohort. To determine the potential role of milk betaine in modulating offspring obesity risk, we performed maternal betaine supplementation experiments in mice. Higher betaine intake during lactation increased milk betaine content in dams and led to lower adiposity and improved glucose homeostasis throughout adulthood in mouse offspring. These effects were accompanied by a transient increase in Akkermansia spp. abundance in the gut during early life and a long-lasting increase in intestinal goblet cell number. The link between breast milk betaine and Akkermansia abundance in the gut was also observed in humans, as infants exposed to higher milk betaine content during breastfeeding showed higher fecal Akkermansia muciniphila abundance. Furthermore, administration of A. muciniphila to mouse pups during the lactation period partially replicated the effects of maternal breast milk betaine, including increased intestinal goblet cell number, lower adiposity, and improved glucose homeostasis during adulthood. These data demonstrate a link between breast milk betaine content and long-term metabolic health of offspring.

Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.

BACKGROUND: Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. METHODS: Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth. FINDINGS: Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study. CONCLUSIONS: The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth. FUNDING: C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.

Distinct maternal microbiota clusters are associated with diet during pregnancy: impact on neonatal microbiota and infant growth during the first 18 months of life.

Nutrition during pregnancy plays an important role in maternal-neonatal health. However, the impact of specific dietary components during pregnancy on maternal gut microbiota and the potential effects on neonatal microbiota and infant health outcomes in the short term are still limited. A total of 86 mother-neonate pairs were enrolled in this study. Gut microbiota profiling on maternal-neonatal stool samples at birth was carried out by 16S rRNA gene sequencing using Illumina. Maternal dietary information and maternal-neonatal clinical and anthropometric data were recorded during the first 18 months. Longitudinal Body Mass Index (BMI) and Weight-For-Length (WFL) z-score trajectories using the World Health Organization (WHO) curves were obtained. The maternal microbiota was grouped into two distinct microbial clusters characterized by Prevotella (Cluster I) and by the Ruminococcus genus (Cluster II). Higher intakes of total dietary fiber, omega-3 fatty acids, and polyphenols were observed in Cluster II compared to Cluster I. Higher intakes of plant-derived components were associated with a higher presence of the Christensellaceae family, Dehalobacterium and Eubacterium, and lower amounts of the Dialister and Campylobacter species. Maternal microbial clusters were also linked to neonatal microbiota and infant growth in a birth-dependent manner. C-section neonates from Cluster I showed the highest BMI z-score at age 18 months, along with a higher risk of overweight. Longitudinal BMI and WL z-score trajectories from birth to 18 months were shaped by maternal microbial cluster, diet, and birth mode. Diet was an important perinatal factor in early life that may impact maternal microbiota; in particular, fiber, lipids and proteins, and exert a significant effect on the neonatal microbiome and contribute to infant development during the first months of life. ABBREVIATIONS: NCDs: Non-Communicable Diseases, C-section: Cesarean Section, BMI: Body Mass Index; WL: Weight for length; EPA: Eicosapentanoic Acid; DHA: Docosahexaenoic Acid; DPA: Docosapentaenoic Acid; SCFA: Short Chain Fatty Acids; MD: Mediterranean Diet; FFQ: Food Frequency Questionnaire; CHI: Calinski Harabasz Index.

Maternal Microbiota, Cortisol Concentration, and Post-Partum Weight Recovery are Dependent on Mode of Delivery.

The importance of the maternal microbiota in terms of the initial bacterial seeding has previously been highlighted; however, little is currently known about the perinatal factors that could affect it. The aim of this study was to evaluate the effects of various delivery-related factors on the intestinal microbiome at delivery time and on post-partum weight retention. Data were collected from mothers (n = 167) during the first four months post-partum. A subset of 100 mothers were selected for the determination of the salivary cortisol concentration and microbiome composition at birth by 16S rRNA gene sequencing. The maternal microbiota was classified into two distinct clusters with significant differences in microbial composition and diversity. Maternal microbiota was also significantly influenced by the mode of delivery. Moreover, the salivary cortisol concentration was associated with some maternal microbiota genera and it was significantly higher in the vaginal delivery group (p = 0.003). The vaginal delivery group exhibited lower post-partum weight retention than the C-section (CS) mothers at four months post-partum (p < 0.001). These results support the hypothesis that the mode of delivery as well as the codominant hormonal changes could influence the maternal microbiota and possibly impact maternal weight recovery during the post-partum period.

Urolithins in Human Breast Milk after Walnut Intake and Kinetics of Gordonibacter Colonization in Newly Born: The Role of Mothers' Urolithin Metabotypes.

The maternal-infant transmission of several urolithins through breast milk and the gut colonization of infants by the urolithin-producing bacterium Gordonibacter during their first year of life were explored. Two trials (proof-of-concept study: n = 11; validation study: n = 30) were conducted, where breastfeeding mothers consumed walnuts as a dietary source of urolithin precursors. An analytical method was developed and validated to characterize the urolithin profile in breast milk. Total urolithins ranged from 8.5 to 176.9 nM, while they were not detected in breast milk of three mothers. The mothers' urolithin metabotypes governed the urolithin profile in breast milk, which might have biological significance on infants. A specific quantitative polymerase chain reaction method allowed monitoring the gut colonization of infants by Gordonibacter during their first year of life, and neither breastfeeding nor vaginal delivery was essential for this. The pattern of Gordonibacter establishment in babies was conditioned by their mother's urolithin metabotype, probably because of mother-baby close contact.

Urolithin Metabotypes Can Determine the Modulation of Gut Microbiota in Healthy Individuals by Tracking Walnuts Consumption over Three Days.

Walnuts are rich in polyphenols ellagitannins, modulate gut microbiota (GM), and exert health benefits after long-term consumption. The metabolism of ellagitannins to urolithins via GM depends on urolithin metabotypes (UM-A, -B, or -0), which have been reported to predict host responsiveness to a polyphenol-rich intervention. This study aims to assess whether UMs were associated with differential GM modulation after short-term walnut consumption. In this study, 27 healthy individuals consumed 33 g of peeled raw walnuts over three days. GM profiling was determined using 16S rRNA illumina sequencing and specific real-time quantitative polymerase chain reactions (qPCRs), as well as microbial activity using short-chain fatty acids analysis in stool samples. UMs stratification of volunteers was assessed using ultra performance liquid chromatography-electro spray ionization-quadrupole time of flight-mass spectrometry (UPLC-ESI-QTOF-MS) analysis of urolithins in urine samples. The gut microbiota associated with UM-B was more sensitive to the walnut intervention. Blautia, Bifidobacterium, and members of the Coriobacteriaceae family, including Gordonibacter, increased exclusively in UM-B subjects, while some members of the Lachnospiraceae family decreased in UM-A individuals. Coprococcus and Collinsella increased in both UMs and higher acetate and propionate production resulted after walnuts intake. Our results show that walnuts consumption after only three days modulates GM in a urolithin metabotype-depending manner and increases the production of short-chain fatty acids (SCFA).

Cofactors of wheat-dependent exercise-induced anaphylaxis do not increase highly individual gliadin absorption in healthy volunteers.

BACKGROUND: In wheat-dependent exercise-induced anaphylaxis (WDEIA), cofactors such as exercise, acetylsalicylic acid (ASA), alcohol or unfavorable climatic conditions are required to elicit a reaction to wheat products. The mechanism of action of these cofactors is unknown, but an increase of gliadin absorption has been speculated. Our objectives were to study gliadin absorption with and without cofactors and to correlate plasma gliadin levels with factors influencing protein absorption in healthy volunteers. METHODS: Twelve healthy probands (six males, six females; aged 20-56 years) ingested 32 g of gluten without any cofactor or in combination with cofactors aerobic and anaerobic exercise, ASA, alcohol and pantoprazole. Gliadin serum levels were measured up to 120 min afterwards and the intestinal barrier function protein zonulin in stool was collected before and after the procedure; both were measured by ELISA. Stool microbiota profile was obtained by 16S gene sequencing. RESULTS: Within 15 min after gluten intake, gliadin concentrations in blood serum increased from baseline in all subjects reaching highly variable peak levels after 15-90 min. Addition of cofactors did not lead to substantially higher gliadin levels, although variability of levels was higher with differences between individuals (p < 0.001) and increased levels at later time points. Zonulin levels in stool were associated neither with addition of cofactors nor with peak gliadin concentrations. There were no differences in gut microbiota between the different interventions, although the composition of microbiota (p < 0.001) and the redundancy discriminant analysis (p < 0.007) differed in probands with low versus high stool zonulin levels. CONCLUSION: The adsorption of gliadin in the gut in healthy volunteers is less dependent on cofactors than has been hypothesized. Patients with WDEIA may have a predisposition needed for the additional effect of cofactors, e.g., hyperresponsive or damaged intestinal epithelium. Alternatively, other mechanisms, such as cofactor-induced blood flow redistribution, increased activity of tissue transglutaminase, or increases in plasma osmolality and acidosis inducing basophil and mast cell histamine release may play the major role in WDEIA.

Urolithin Metabotypes can Anticipate the Different Restoration of the Gut Microbiota and Anthropometric Profiles during the First Year Postpartum.

The metabolism of dietary polyphenols ellagitannins by the gut-microbiota allows the human stratification in urolithin metabotypes depending on the final urolithins produced. Metabotype-A only produces urolithin-A, metabotype-B yields urolithin-B and isourolithin-A in addition to urolithin-A, and metabotype 0 does not produce urolithins. Metabotype-A has been suggested to be 'protective', and metabotype-B dysbiotic-prone to cardiometabolic impairments. We analyzed the gut-microbiome of 40 healthy women and determined their metabotypes and enterotypes, and their associations with anthropometric and gut-microbial changes after 3 weeks, 4, 6, and 12 months postpartum. Metabotype-A was predominant in mothers who lost weight (≥2 kg) (75%) versus metabotype-B (54%). After delivery, the microbiota of metabotype-A mothers changed, unlike metabotype-B, which barely changed over 1 year. The metabotype-A discriminating bacteria correlated to the decrease of the women's waist while some metabotype-B bacteria were inversely associated with a reduction of body mass index (BMI), waist, and waist-to-hip ratio. Metabotype-B was associated with a more robust and less modulating microbial and anthropometric profiles versus metabotype-A, in which these profiles were normalized through the 1-year follow-up postpartum. Consequently, urolithin metabotypes assessment could be a tool to anticipate the predisposition of women to normalize their anthropometric values and gut-microbiota, significantly altered during pregnancy and after childbirth.

Deciphering the Human Gut Microbiome of Urolithin Metabotypes: Association with Enterotypes and Potential Cardiometabolic Health Implications.

SCOPE: The gut microbiota ellagitannin-metabolizing phenotypes (i.e., urolithin metabotypes [UMs]) are proposed as potential cardiovascular disease (CVD) risk biomarkers because the host blood lipid profile is reported to be associated with specific UMs. However, the link for this association remains unknown so far. METHODS AND RESULTS: The gut microbiome of 249 healthy individuals is analyzed using 16S rDNA sequencing analysis. Individuals are also stratified by UMs (UM-A, UM-B, and UM-0) and enterotypes (Bacteroides, Prevotella, and Ruminococcus). Associations of UMs discriminating bacteria with CVD risk markers are investigated. Distribution and gut microbiota composition of UMs and enterotypes are not coincident. Almost half of the discriminating genera between UM-A and UM-B belongs to the Coriobacteriaceae family. UM-B individuals present higher blood cholesterol levels and higher alpha-diversity, including Coriobacteriaceae family, than those of UM-A. Coriobacteriaceae, whose abundance is the highest in UM-B, is positively correlated with total cholesterol, LDL cholesterol, and body mass index. CONCLUSIONS: Results herein suggest that the family Coriobacteriaceae could be a link between individuals' UMs and their blood cholesterol levels. Further research is needed to explore the mechanisms of the host metabolic phenotype, including cholesterol excretion products, to modulate this bacterial family.