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© 2020 by the authors., The gut microbiota (GM) has attracted attention as a new target to combat several diseases, including metabolic syndrome (MetS), a pathological condition with many factors (diabetes, obesity, dyslipidemia, hypertension, etc.) that increase cardiovascular disease (CVD) risk. However, the existence of a characteristic taxonomic signature associated with obesity-related metabolic dysfunctions is under debate. To investigate the contribution of the CVD risk factors and(or) their associated drug treatments in the composition and functionality of GM in MetS patients, we compared the GM of obese individuals (n = 69) vs. MetS patients (n = 50), as well as within patients, depending on their treatments. We also explored associations between medication, GM, clinical variables, endotoxemia, and short-chain fatty acids. Poly-drug treatments, conventional in MetS patients, prevented the accurate association between medication and GM profiles. Our results highlight the heterogeneity of taxonomic signatures in MetS patients, which mainly depend on the CVD risk factors. Hypertension and(or) its associated medication was the primary trait involved in the shaping of GM, with an overabundance of lipopolysaccharide-producing microbial groups from the Proteobacteria phylum. In the context of precision medicine, our results highlight that targeting GM to prevent and(or) treat MetS should consider MetS patients more individually, according to their CVD risk factors and associated medication., This research was funded by MINECO (Spain), grant number AGL2015-64124-R, and Fundación Séneca de la Región de Murcia (Spain), grant number 20880/PI/18. A.C.M. is the holder of a predoctoral grant from MINECO (Spain).

Understanding individuals' response to dietary bioactives is crucial for personalized nutrition. We report here for the first time in a Caucasian cohort (5-90 years, n = 839) that aging is the main factor that determines the gut microbiota involved in the ellagic acid-ellagitannin metabolism (urolithin metabotypes), with potential consequences for human health.

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 &lsquo, protective&rsquo, 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 (&ge, 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&rsquo, 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.

Scope: Poly-pharmacological therapy shapes the gut microbiota (GM) in metabolic syndrome (MetS) patients. The effects of polyphenols in poly-medicated MetS patients are unknown. Methods and results: A randomized, placebo-controlled, double-blinded, and crossover trial in poly-medicated MetS patients (n=50) explored whether the effects of a pomegranate extract nutraceutical (PE, 320 mg phenolics/day for 1 month) are affected by the drug therapy. Considering the lipid-lowering (LL-), anti-hypertensive (HP-) and(or) anti-diabetic (AD-) treatments: GM (16S rRNA sequencing), short-chain fatty acids, 40 inflammatory-metabolic and endotoxemia-related biomarkers, associations between biomarkers and GM with 53 cardiometabolic dysfunctions-related single-nucleotide polymorphisms (SNPs), and urolithin metabotypes (UMs) influence are evaluated. Representative SNPs-GM associations after PE include Lactococcus and ClostridiumXIVa with rs5443-GNB3 (G-protein-β-polypeptide-3) and ClostridiumXIVa with rs7903146-TCF7L2 (transcription-factor-7-like-2) and rs1137101-LEPR (leptin-receptor). PE decreases sICAM-1 in LL-patients and the lipopolysaccharide-binding protein in all the patients. PE does not affect the other patients’ markers as a group or stratifying by UMs. After PE, Lactococcus increases in AD-, LL-, and HP-patients, Bifidobacterium increases in LL- and AD-, while Clostridium XIVa decreases in non-LL- and non-HP-patients. Conclusion: The prebiotic effect of PE depends on the medication, mainly on HP-treatments. Targeting GM can complement MetS therapy, but the patients’ drug therapy should be considered individually., Ministerio de Economía y Competitividad. Grant Number: AGL2015-94124-R Fundación Séneca. Grant Number: 20880/PI/18 Ministerio de Ciencia e Innovación. Grant Number: PID2019-103914RB-I00

The full consensus on the role of dietary polyphenols as human-health-promoting compounds remains elusive. The two-way interaction between polyphenols and gut microbiota (GM) (i.e., modulation of GM by polyphenols and their catabolism by the GM) is determinant in polyphenols' effects. The identification of human metabotypes associated with a differential gut microbial metabolism of polyphenols has opened new research scenarios to explain the inter-individual variability upon polyphenols consumption. The metabotypes unequivocally identified so far are those involved in the metabolism of isoflavones (equol and(or) O-desmethylangolesin producers versus non-producers) and ellagic acid (urolithin metabotypes, including producers of only urolithin-A (UM-A), producers of urolithin-A, isourolithin-A, and urolithin-B (UM-B), and non-producers (UM-0)). In addition, the microbial metabolites (phenolic-derived postbiotics) such as equol, urolithins, valerolactones, enterolactone, and enterodiol, and 8-prenylnaringenin, among others, can exert differential health effects. The knowledge is updated and position is taken here on i) the two-way interaction between GM and polyphenols, ii) the evidence between phenolic-derived postbiotics and health, iii) the role of metabotypes as biomarkers of GM and the clustering of individuals depending on their metabotypes (metabotyping) to explain polyphenols' effects, and iv) the gut microbial metabolism of catecholamines to illustrate the intersection between personalized nutrition and precision medicine.

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.

SCOPE: The stratification of individuals according to their gut microbiota metabotypes is crucial to understand the polyphenols health effects as reported for isoflavones and ellagitannins. To date, the existence of human gut microbiota metabotypes associated with proanthocyanidins (PAs) catabolism remains unclear. METHODS & RESULTS: Sixty‐eight healthy volunteers (40 adolescents and 28 adults) consumed a mixture of walnuts, almonds, and hazelnuts for 3 days, providing 163.65 ± 11.74 mg of PAs. Urine samples were analyzed by ultra‐performance LC–ESI‐quadrupole time‐of‐flight. Twenty‐one isomers of conjugated valerolactones and valeric acids were identified, which derived from six valerolactone and valeric acid precursors after analysis of hydrolyzed urine. This combined approach allowed discrimination between the inter‐individual variability related to phase‐II enzymes polymorphisms and the metabolism of PAs by the gut microbiota. No associations of PAs metabolism with gender, age, BMI, or ellagitannin metabotypes were found. Different quantitative excretion was observed after multivariate analysis but not true gut microbiota metabotypes associated with PAs catabolism. CONCLUSIONS: The metabolism of PAs does not reveal urinary metabolites consistent with distinctive gut microbiota metabotypes. The quantitative excretion of metabolites is inadequate to stratify individuals due to the strong influence of external factors (source, quantity, and time of the last intake of PAs, etc.).

SCOPE: Gut microbiota dysbiosis, intestinal barrier failure, obesity, metabolic endotoxemia, and pro‐inflammatory status promote cardiovascular risk. However, the modulation of the gut microbiome to prevent endotoxemia in obesity has been scarcely studied. We investigated the association between gut microbiota modulation and plasma lipopolysaccharide‐binding protein (LBP), a surrogate marker of endotoxemia, in overweight‐obese individuals. METHODS AND RESULTS: In a randomized trial, 49 overweight‐obese subjects (body mass index> 27 kg m⁻²) with mild hypelipidemia daily consumed, in a cross‐over fashion, two doses (D1 and D2, lasting 3 weeks each) of pomegranate extract (PE) or placebo alternating with 3 weeks of wash‐out periods. A significant decrease (p < 0.05) of plasma LBP and a marginal decrease (p = 0.054) of high‐sensitivity C‐reactive protein were observed, but only after PE‐D2 administration (656 mg phenolics). 16S rDNA sequencing analyses revealed the increase of microorganisms important for maintaining normal balance of gut microbiota and gut barrier function, particularly Bacteroides, Faecalibacterium, Butyricicoccus, Odoribacter, and Butyricimonas. PE‐D2 also decreased pro‐inflammatory microorganisms including Parvimonas, Methanobrevibacter, and Methanosphaera. Remarkably, plasma LBP reduction was significantly associated (p < 0.05) with both Faecalibacterium and Odoribacter increase and Parvimonas decrease. CONCLUSIONS: Consumption of PE decreased endotoxemia in overweight‐obese individuals by reshaping the gut microbiota, mainly through the modulation of Faecalibacterium, Odoribacter, and Parvimonas.

The purpose of this study was to determine the frequency of emerging parasites in two groups of immunosuppressed patients, including individuals infected with the human immunodeficiency virus (AIDS) (HIV) or having acute lymphoblastic leukemia (ALL) with or without diarrhea. Stool samples were collected from 96 HIV and 77 ALL patients from March 2010 through December 2011. Screening for opportunistic parasites was carried out by the coproparasitoscopic Faust method, Ziehl Neelsen staining, and Polymerase Chain Reaction (PCR). Results showed that 22.9% of HIV fecal samples were positive for emerging parasites, including Cryptosporidium spp. (7.3%), Microsporidium spp. (5.2%), Isospora belli (1.0%), Giardia intestinalis (2.6%), and Cyclospora spp. (7.3%). On the other hand, 32.5% of ALL fecal samples were positive for emerging parasites, including Cryptosporidium spp. (9.1%), Microsporidium spp. (19.5%), Isospora belli (1.3%), and Giardia intestinalis (2.6%). Our results highlighted the need for specific, efficient, and reliable diagnostic methods to identify the presence of emerging parasites in immunocompromised patients susceptible to different infectious diseases or neoplastic processes and avoid the consequences for the host as an increased disease rate, alterations in the clinical manifestation of the infection or even exacerbation of its course.

The purpose of this investigation was to determine the intestinal parasite prevalence in puppies from six different kennels; four kennels were in Guadalajara and Zapopan cities (Jalisco State) and two kennels were in Mexico City. From October 2006 to November 2007, we collected 441 fecal samples from 147 puppies, both male and female, ranging from 1 to 36 months of age. Three samples from every puppy were analyzed by using the Faust technique. The prevalence found were as follows: Giardia intestinalis (genotype A and B) 6.8%; Cystoisospora 21.08%; Uncinaria 7.48%; Toxocara canis 12.29% and multiparasitism (Giardia, Toxocara and Uncinaria) 4.76%. The highest prevalence for both Giardia and Cystoisospora were found in 2-3- month-old puppies; the highest prevalence for Toxocara canis was found in 3-4-month-old puppies. In the kennels of Mexico City we found mainly Giardia intestinalis, Cystoisospora to be most prevalent in Zapopan and Toxocara canis in Guadalajara. The high prevalence of intestinal parasites found in this study demonstrates an increased risk for infection in humans, as these animals are usually a common pet in many homes. This zoonotic phenomenon represents an important health problem for any community.

The assemblage of 37 Giardia intestinalis samples was determined, 19 obtained from puppy feces, 12 from stools of different human subjects under 3 years of age and 6 from axenic culture. The assemblages were classified according to the restriction pattern of beta-giardin gene with Hae III enzyme. Results showed that dog assemblages were grouped AI (52.6%) and AII (47.4%), while 41.7% human samples belonged to genotype AI and 58.3% to genotype AII. All axenic cultures belonged to assemblage AI; types AI and AII were both found in dog and human feces by Hae III restriction enzyme assay, suggesting a similarity between human and dog parasites. These results suggest that domestic animals infected with Giardia could produce cysts potentially infective for humans.

Agarose gel electrophoresis of gdh gene fragments, amplified by Multiplex, was used to classify the assemblage of 24 Giardia isolates obtained from axenic cultures, children's stools, and feces of puppies from different dog breeds. Isolates were compared with seven reference strains of Giardia intestinalis. The results showed that 22/24 isolates (91%) belonged to assemblage A and could be further subclassified as assemblage A1 (18/22, 81%) and assemblage A2 (4/22, 19%). One sample revealed a mixture of A1/A2 genotypes, and another was assemblage G, indicating mixed infections by different strains in the same host, and an association with the assemblage reported in animals. The procedure described is useful to determine the Giardia genotype that parasitizes each host to conduct epidemiological studies assessing the close association between human- and animal-infecting strains and to monitor the adaptability of animal strains to humans.

Giardia intestinalis, a flagellated protozoan parasite, is the most prevalent human intestinal protozoan worldwide (Adam, 2001). About 200 million people in the world are infected with giardiasis and each individual eliminates up to 900 million cysts per day (Minivielle , 2008). Higher prevalence is found in tropical and subtropical areas, where Giardia affects up to 30% of the population. In epidemiological studies carried out in Mexico and other sudamerican countries, prevalence between of 10-16% has been found in urban areas and 34% in shantytowns (Gamboa “et al”, 2003; Giraldo-Gomez, 2005; Sulaiman, 2004). G. intestinalis is a cosmopolitan pathogen with a very wide host range, including humans, domestic animals, and wild animal species (Caccio, 2008; Thompson, et al 1993). The most common cause of infection with Giardia is the consumption of contaminated food or water (Ortega, 1997), although zoonotic transmission is also possible. Once a person is infected, the parasite lives in the intestines and is passed in the stool of the infected person. Animals such as cats, dogs and cattle can also be infected and spread the disease to humans.

The presence of human Giardia in several animals suggests a zoonotic transmission. We studied G. Intestinalis isolates obtained from: children with diarrhea (n=6), asymptomatic children (n=7), axenic cultures (n=7) and dogs (n=11). The sequence corresponding to 16 S rRNA was amplified by PCR, sequenced and compared with genotypes A, B and Dog sequences reported in the Gene Bank database. Results show that 9/20 (45%) of children isolates belonged to genotype A and 11/20 (55%) showed some variable sites, allowing classification in three arbitrary clusters: A1, A2 and A3. In addition 7/11 (63%) of dog isolates were genotype A, including those dogs that lived in the same locality as the children lived, while 4/11 (37%) belonged to an arbitrary A4 cluster living in a different locality. In this study, genotype A was associated with samples from children and dogs, and, therefore, we could infer zoonotic transmission as a way of getting the disease.

Despite the high human interindividual variability in response to (poly)phenol consumption, the cause-and-effect relationship between some dietary (poly)phenols (flavanols and olive oil phenolics) and health effects (endothelial function and prevention of LDL oxidation, respectively) has been well established. Most of the variables affecting this interindividual variability have been identified (food matrix, gut microbiota, single-nucleotide-polymorphisms, etc.). However, the final drivers for the health effects of (poly)phenol consumption have not been fully identified. At least partially, these drivers could be (i) the (poly)phenols ingested that exert their effect in the gastrointestinal tract, (ii) the bioavailable metabolites that exert their effects systemically and/or (iii) the gut microbial ecology associated with (poly)phenol metabolism (i.e., gut microbiota-associated metabotypes). However, statistical associations between health effects and the occurrence of circulating and/or excreted metabolites, as well as cross-sectional studies that correlate gut microbial ecologies and health, do not prove a causal role unequivocally. We provide a critical overview and perspective on the possible main drivers of the effects of (poly)phenols on human health and suggest possible actions to identify the putative actors responsible for the effects., This research was supported by the Project PID2019-103914RB-I00 from the Ministry of Science and Innovation (MICINN, Spain) and by Fundación Séneca de la Región de Murcia (Spain), grant number 20880/PI/18. J.A.G.-B. was supported by a Standard European Marie Curie Fellowship from the European Commission. This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 838991. A.C.M. and C.E.I.-A. are the holders of predoctoral grants from MINECO (grant number BES-2016-078098) and MICINN (grant number FPU18/03961) (Spain), respectively