Alteration of Gut Microbiota Composition in the Progression of Liver Damage in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota-gut-liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F-), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and ß-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F- and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F- and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.

Development and Relative Validation of a Food Frequency Questionnaire to Assess Non-Nutritive Sweeteners Intake among Pregnant Women in Santiago, Chile: A Pilot Study.

Studies on the effects of non-nutritive sweeteners (NNSs) among pregnant women are scarce and have produced mixed results. One of the major challenges is to accurately assess NNS intake, especially in countries that have implemented policies to prevent obesity and where many foods and beverages have been progressively reformulated to partially or totally replace sugar with NNSs. This study aimed to develop and assess the relative validity of a food frequency questionnaire (FFQ) for use in pregnant women. We developed an FFQ to examine the intake of seven NNSs (acesulfame-k, aspartame, cyclamate, saccharin, sucralose, steviol glycosides, and D-tagatose). This questionnaire was piloted in 29 pregnant women (median age = 31.2 y; 25th-75th percentile: 26.9-34.7) to assess NNS intake over the previous month, compared to 3-day dietary records (3-DR). The validity of this dietary method was assessed using Spearman's correlation coefficient, Lin´s concordance correlation coefficient (CCC), and Bland-Altman plots. Spearman's correlations between the FFQ on NNSs and 3-DR ranged from 0.50 for acesulfame K to 0.83 for saccharin. CCC ranged between 0.22 and 0.66. The Bland-Altman plots showed an overestimation of saccharin, sucralose, and steviol glycosides intake by the FFQ on NNSs compared with 3-DR, and an underestimation of acesulfame K and aspartame. Overall, the NNSs most frequently consumed were sucralose, and none of the participants exceeded the acceptable daily intake for any of the NNSs evaluated. The FFQ on NNSs seems to be reasonably valid in the assessment of NNSs among pregnant women.

Curated and harmonized gut microbiome 16S rRNA amplicon data from dietary fiber intervention studies in humans.

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide curated and pre-processed genetic data and common metadata for comparison across the different studies.

Maternal consumption and perinatal exposure to non-nutritive sweeteners: should we be concerned?

The context for this review is the rapid increase in the use of non-nutritive sweeteners (NNSs) instead of sugar in foods and beverages, a situation so prevalent in some countries that consumers are finding it increasingly challenging to access foods without NNSs. The benefits of consuming NNSs on obesity and diabetes are now being questioned, and studies have shown that they may exert physiological activities, sometimes independently of sweet taste receptor stimulation. Few studies, limited mainly to North American and European countries, have described the consumption of NNSs by pregnant or lactating women and infants. Most focus on beverages rather than foods, but all agree that consumption levels have increased dramatically. Although some studies report a negative impact of NNSs on the risk of preterm birth, increased birth weight and decreased gestational age, the level of evidence is low. Several studies have also reported increased weight gain in infancy, associated with maternal NNS intake. Interestingly, several NNSs have been detected in amniotic fluid and breast milk, usually (but not always) at concentrations below their established detection limit in humans. Unfortunately, the impact of chronic exposure of the fetus/infant to low levels of multiple NNSs is unknown. In conclusion, there is a stark contrast between the galloping increase in the consumption of NNSs and the small number of studies evaluating their impact in at-risk groups such as pregnant and lactating women and infants. Clearly, more studies are needed, especially in Latin America and Asia, to fill these gaps and update recommendations.

Modulation of Postprandial Plasma Concentrations of Digestive Hormones and Gut Microbiota by Foods Containing Oat ß-Glucans in Healthy Volunteers.

Cereal ß-glucans are beneficial health ingredients that reduce cholesterolemia and postprandial glycaemia. However, their impact on digestive hormones and gut microbiota is not yet fully established. Two randomized, double-blind, controlled studies were conducted. In the first study, 14 subjects ingested a breakfast with or without ß-glucan from oats (5.2 g). Compared to the control, ß-glucan increased orocecal transit time (p = 0.028) and decreased mean appetite score (p = 0.014) and postprandial plasma ghrelin (p = 0.030), C-peptide (p = 0.001), insulin (p = 0.06), and glucose (p = 0.0006). ß-glucan increased plasma GIP (p = 0.035) and PP (p = 0.018) without affecting leptin, GLP-1, PYY, glucagon, amylin, or 7α-hydroxy-4-cholesten-3-one, a biomarker of bile acid synthesis. In the second study, 32 subjects were distributed into 2 groups to ingest daily foods with (3 g/day) or without ß-glucan for 3 weeks; stools were collected before/after treatment. No changes in fecal microbiota composition/diversity (deep sequencing) were detected with ß-glucans. These results indicate that acute intake of 5 g ß-glucan slows transit time and decreases hunger sensation and postprandial glycaemia without affecting bile-acid synthesis, these changes being associated with decreased plasma insulin, C-peptide, and ghrelin, and increased plasma GIP and PP. However, regular daily intake of 3 g ß-glucan is not sufficient to have an effect on fecal microbiota composition.

Metabolic Modeling and Bidirectional Culturing of Two Gut Microbes Reveal Cross-Feeding Interactions and Protective Effects on Intestinal Cells.

The gut microbiota is constituted by thousands of microbial interactions, some of which correspond to the exchange of metabolic by-products or cross-feeding. Inulin and xylan are two major dietary polysaccharides that are fermented by members of the human gut microbiota, resulting in different metabolic profiles. Here, we integrated community modeling and bidirectional culturing assays to study the metabolic interactions between two gut microbes, Phocaeicola dorei and Lachnoclostridium symbiosum, growing in inulin or xylan, and how they provide a protective effect in cultured cells. P. dorei (previously belonging to the Bacteroides genus) was able to consume inulin and xylan, while L. symposium only used certain inulin fractions to produce butyrate as a major end product. Constrained-based flux simulations of refined genome-scale metabolic models of both microbes predicted high lactate and succinate cross-feeding fluxes between P. dorei and L. symbiosum when growing in each fiber. Bidirectional culture assays in both substrates revealed that L. symbiosum growth increased in the presence of P. dorei. Carbohydrate consumption analyses showed a faster carbohydrate consumption in cocultures compared to monocultures. Lactate and succinate concentrations in bidirectional cocultures were lower than in monocultures, pointing to cross-feeding as initially suggested by the model. Butyrate concentrations were similar across all conditions. Finally, supernatants from both bacteria cultured in xylan in bioreactors significantly reduced tumor necrosis factor-α-induced inflammation in HT-29 cells and exerted a protective effect against the TcdB toxin in Caco-2 epithelial cells. Surprisingly, this effect was not observed in inulin cocultures. Overall, these results highlight the predictive value of metabolic models integrated with microbial culture assays for probing microbial interactions in the gut microbiota. They also provide an example of how metabolic exchange could lead to potential beneficial effects in the host. IMPORTANCE Microbial interactions represent the inner connections in the gut microbiome. By integrating mathematical modeling tools and microbial bidirectional culturing, we determined how two gut commensals engage in the exchange of cross-feeding metabolites, lactate and succinate, for increased growth in two fibers. These interactions underpinned butyrate production in cocultures, resulting in a significant reduction in cellular inflammation and protection against microbial toxins when applied to cellular models.

Interference of dietary polyphenols with potentially toxic amino acid metabolites derived from the colonic microbiota.

Each day, varying amounts of undigested or partially digested proteins reach the colon where they are metabolized by the microbiota, resulting in the formation of compounds such as ammonia, p-cresol, skatole, phenol, indole, and hydrogen sulfide (H2S). In farm animals, the excessive production of these metabolites can affect the quality of meat and milk and is a source of contaminating emissions from animal manure. In humans, their accumulation is potentially harmful, and it has been proposed that they could be involved in the development of pathologies such as colorectal cancer and ulcerative colitis, among others. This review assesses the evidence supporting the use of dietary polyphenols to reduce the production of these metabolites. Most studies have used condensed (proanthocyanidins) or hydrolyzable (ellagitannins and gallotannins) tannins, and have been carried out in farm animals. Several show that the administration of tannins in pigs, chicken, and ruminants decreases the levels of ammonia, p-cresol, skatole, and/or H2S, improving meat/milk quality and reducing manure odor. Direct application of tannins to manure also decreases ammonia emissions. Few studies were carried out in rats and humans and their results confirm, to a lesser extent, those reported in farm animals. These effects would be due to the capacity of tannins to trap ammonia and H2S, and to modify the composition of the microbiota, reducing the bacterial populations producing metabolites. In addition, PACs prevent p-cresol and H2S-induced alterations on intestinal cells in vitro. Tannins, therefore, appear as an interesting tool for improving the quality of animal products, human health, and the harmful emissions associated with breeding.

Improvement in Lactose Tolerance in Hypolactasic Subjects Consuming Ice Creams with High or Low Concentrations of Bifidobacterium bifidum 900791.

Although Bifidobacterium bifidum expresses lactase activity, no clinical trials have determined its impact on lactose-intolerant subjects. This study evaluated whether acute and chronic ingestion of ice creams containing B. bifidum 900791 at high (107 CFU/g) or low (105 CFU/g) concentrations improved lactose tolerance in hypolactasic subjects. Fifty subjects were selected based on a positive lactose (20 g) hydrogen breath test (HBT0) and the presence of digestive symptoms. The recruited subjects were required to perform breath tests after the acute ingestion of: (1) ice cream containing 20 g of lactose without a probiotic (HBT1); (2) the same ice cream, accompanied by a lactase tablet (HBT2); (3) the same ice cream containing the low or high dose of probiotic (HBT3-LD and HBT3-HD); and (4) after the chronic consumption of the ice cream without (placebo) or with the low concentration of probiotic for 1 month (HBT4). Significant decreases in H2 excretion during HBT2 and HBT3-HD as well as digestive symptoms during HBT2, HBT3-HD and HBT3-LD were observed compared to HBT0 and HBT1, while the orocecal transit time increased. Chronic consumption of the probiotic ice cream did not enhance lactose tolerance compared to the placebo. These results suggest that the acute ingestion of ice cream containing high or low concentrations of B. bifidum 900791 improves lactose tolerance in hypolactasic subjects.

Butyrate and the Fine-Tuning of Colonic Homeostasis: Implication for Inflammatory Bowel Diseases.

This review describes current evidence supporting butyrate impact in the homeostatic regulation of the digestive ecosystem in health and inflammatory bowel diseases (IBDs). Butyrate is mainly produced by bacteria from the Firmicutes phylum. It stimulates mature colonocytes and inhibits undifferentiated malignant and stem cells. Butyrate oxidation in mature colonocytes (1) produces 70-80% of their energetic requirements, (2) prevents stem cell inhibition by limiting butyrate access to crypts, and (3) consumes oxygen, generating hypoxia and maintaining luminal anaerobiosis favorable to the microbiota. Butyrate stimulates the aryl hydrocarbon receptor (AhR), the GPR41 and GPR109A receptors, and inhibits HDAC in different cell types, thus stabilizing the gut barrier function and decreasing inflammatory processes. However, some studies indicate contrary effects according to butyrate concentrations. IBD patients exhibit a lower abundance of butyrate-producing bacteria and butyrate content. Additionally, colonocyte butyrate oxidation is depressed in these subjects, lowering luminal anaerobiosis and facilitating the expansion of Enterobacteriaceae that contribute to inflammation. Accordingly, gut dysbiosis and decreased barrier function in IBD seems to be secondary to the impaired mitochondrial disturbance in colonic epithelial cells.

Comparison of Argentinean microbiota with other geographical populations reveals different taxonomic and functional signatures associated with obesity.

Accumulating evidence suggests that various genetic and environmental factors contribute to the development of obesity. Among the latter, the gut microbiota has emerged as a critical player in the regulation of human metabolism and health and the development of non-communicable chronic diseases. Considering that no information on this matter is available in Argentina, our aim was to identify the microorganisms associated with obesity as well as their potential functionality. Using high throughput sequencing of 16SrRNA bacterial gene and diverse bioinformatics tools, we observed that the gut microbiota of obese and overweight individuals differs qualitatively and quantitatively from that from their lean counterparts. The comparison of the gut microbiota composition in obese subjects from Argentina, US and UK showed that the beta diversity significantly differs among the three countries, indicating that obesity-associated microbiota composition changes according to the geographical origin of the individuals. Moreover, four distinct microbiotypes were identified in obese individuals, whose prevalence and metabolic pathway signature differed according to the country, indicating that obesity associated dysbiosis would comprise several structures. In summary, identification of distinct taxonomic signatures associated with obesity might be a novel promising tool to stratify patients based on their microbiome configuration to design strategies for managing obesity.

Quercetin Oxidation Metabolite Present in Onion Peel Protects Caco-2 Cells against the Oxidative Stress, NF-kB Activation, and Loss of Epithelial Barrier Function Induced by NSAIDs.

The potential of 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (BZF), a quercetin oxidation metabolite, and that of a BZF-rich onion peel aqueous extract (OAE) to protect Caco-2 monolayers against the oxidative stress (OS) and an increased permeability (IP) induced by five nonsteroidal anti-inflammatory drugs (NSAIDs) (indomethacin, diclofenac, piroxicam, ibuprofen, and metamizole) were investigated. Under identical OS conditions, the NSAIDs substantially differed in their ability to induce an IP and/or NF-kB activation. The OAE (100 nM BZF) protected in identical magnitude (84-86%) against OS but in a highly dissimilar manner against the IP (18-73%). While all NSAIDs activated NF-kB, the OAE prevented only that induced by indomethacin. Results reveal that the IP has no direct relationship with the OS and that with the exception of indomethacin, the prevention of NSAIDs-induced OS and/or NF-kB activation plays no fundamental role in the IP-protecting effect of OAE. These results warrant the in vivo evaluation of OAE against indomethacin-induced loss of intestinal barrier function.

Polyphenols and their anti-obesity role mediated by the gut microbiota: a comprehensive review.

Obesity is a global public health problem that results in chronic pathologies such as diabetes, cardiovascular diseases, and cancer. The treatment approach based on energy restriction and promotion of physical activity is ineffective in the long term. Due to the high prevalence of this pathology, complementary treatments such as brown adipose tissue activation (BAT) and white adipose tissue browning (WAT) have been proposed. Dietary polyphenols are plant secondary metabolites that can stimulate browning and thermogenesis of adipose tissue. They have also been shown to prevent body weight gain, and decrease systemic inflammation produced by high-fat diets. Ingested dietary polyphenols that reach the colon are metabolized by the gut microbiota (GM), regulating its composition and generating a great array of metabolites. GM is involved in the production of short chain fatty acids and secondary bile salts that regulate energetic metabolism. The alteration in the composition of GM observed in metabolic diseases such as obesity and type 2 diabetes can be attenuated by polyphenols. Recent studies support the hypothesis that GM would mediate WAT browning and BAT thermogenesis activation induced by polyphenol administration. Together, these results indicate that GM in the presence of polyphenols plays a fundamental role in the control of obesity possible through BAT activation.

The Pros and Cons of Using Algal Polysaccharides as Prebiotics.

Macroalgae stand out for their high content of dietary fiber (30-75%) that include soluble, sulfated (fucoidan, agaran, carrageenan, and ulvan) and non-sulfated (laminaran and alginate) polysaccharides. Many studies indicate that these compounds exert varied biological activities and health-promoting effects and for this reason, there is a growing interest for using them in food products. The aim of this review was to critically evaluate prebiotic properties of algal polysaccharides, i.e., their ability to exert biological activities by modulating the composition and/or diversity of gut microbiota (GM). Pre-clinical studies show that the non-sulfated alginate and laminaran are well-fermented by GM, promoting the formation of short chain fatty acids (SCFAs) including butyrate, and preventing that of harmful putrefactive compounds (NH3, phenol, p-cresol, indole and H2S). Alginate increases Bacteroides, Bifidobacterium, and Lactobacillus species while laminaran mostly stimulates Bacteroides sp. Results with sulfated polysaccharides are more questionable. Agarans are poorly fermentable but agarose-oligosaccharides exhibit an interesting prebiotic potential, increasing butyrate-producing bacteria and SCFAs. Though carrageenan-oligosaccharides are also fermented, their use is currently limited due to safety concerns. Regarding fucoidan, only one study reports SCFAs production, suggesting that it is poorly fermented. Its effect on GM does not indicate a clear pattern, making difficult to conclude whether it is beneficial or not. Notably, fucoidan impact on H2S production has not been evaluated, though some studies report it increases sulfate-reducing bacteria. Ulvan is badly fermented by GM and some studies show that part of its sulfate is dissimilated to H2S, which could affect colonic mitochondrial function. Accordingly, these results support the use of laminaran, alginate and agaro-oligosaccharides as prebiotics while more studies are necessary regarding that of fucoidan, carrageenan and ulvan. However, the realization of clinical trials is necessary to confirm such prebiotic properties in humans.

Overuse of Non-caloric Sweeteners in Foods and Beverages in Chile: A Threat to Consumers' Free Choice?

The prevalence of obesity among Chilean adults and children is one of the highest worldwide. To fight the constant increase of non-communicable diseases and the growing sales of sugar-sweetened beverages, the Chilean government recently enacted a new Law of Food Labeling and Advertising imposing the application of front-of-package warning labels in foodstuffs whose composition exceeds limits for critical nutrients including sugar. Accordingly, food companies have been reformulating their products, incorporating non-caloric sweeteners (NCSs) in partial or total replacement of sucrose. The number of NCS-containing foods and beverages, therefore, has been increasing in the last years. This study aims to identify the NCS-containing products from different food/beverage categories currently available on the Chilean market. Nineteen supermarkets and 13 food web pages were visited by trained dietitians to carry out a systematic search of ingredient information from the different food categories. Overall, 1,489 products were analyzed, of which 815 (55.5%) contained at least one NCS, being this proportion particularly high, compared to other countries. 67.1% of the dairy products, 31.5% of the cereal products, 49% of the processed fruits, 74.3% of the non-alcoholic beverages, and 46.2% of sweets and other desserts contained NCS. Considering the food categories more specifically oriented to children, NCSs were present in 98.8% of powder juices, 98.3% of the flavored milks, 91.2% of jellies, and 79% of the dairy desserts. Sucralose and steviol glycosides were the most widely used NCSs, these sweeteners being present, alone or mixed with other, in 73.5 and 39.7% of the NCS-containing products, respectively, while the use of saccharin and cyclamate was low. In addition, 80 tabletop NCSs were available in the local market, 91.2% of them being sucralose and steviol glycosides (alone or combined). The high number of food products containing steviol glycosides makes very plausible that the daily consumption of this NCS in the pediatric populations could exceed its acceptable daily intake (ADI). The fact that there are no NCS-free foods alternatives for certain food categories, especially for children, is worrying.

The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?

The gut microbiota is emerging as a promising target for the management or prevention of inflammatory and metabolic disorders in humans. Many of the current research efforts are focused on the identification of specific microbial signatures, more particularly for those associated with obesity, type 2 diabetes, and cardiovascular diseases. Some studies have described that the gut microbiota of obese animals and humans exhibits a higher Firmicutes/Bacteroidetes ratio compared with normal-weight individuals, proposing this ratio as an eventual biomarker. Accordingly, the Firmicutes/Bacteroidetes ratio is frequently cited in the scientific literature as a hallmark of obesity. The aim of the present review was to discuss the validity of this potential marker, based on the great amount of contradictory results reported in the literature. Such discrepancies might be explained by the existence of interpretative bias generated by methodological differences in sample processing and DNA sequence analysis, or by the generally poor characterization of the recruited subjects and, more particularly, the lack of consideration of lifestyle-associated factors known to affect microbiota composition and/or diversity. For these reasons, it is currently difficult to associate the Firmicutes/Bacteroidetes ratio with a determined health status and more specifically to consider it as a hallmark of obesity.

Fitoquímicos: una nueva clase de prebióticos / Phytochemicals: a new class of prebiotics

RESUMEN La microbiota intestinal (MI) es considerada como un nuevo blanco para la prevención y manejo nutricional de las alteraciones inflamatorias y metabólicas asociadas a las enfermedades crónicas no-transmisibles. Los prebióticos son principalmente fibras solubles cuyo consumo favorece el crecimiento de poblaciones bacterianas beneficiosas de la MI e impacta favorablemente la salud del consumidor. Esta revisión presenta a los fitoquímicos dietarios, que incluyen a más de 8.000 compuestos, como una nueva clase de prebióticos debido a su capacidad de estimular poblaciones de Lactobacillus, Bifidobacterium, Akkermansia y de bacterias productoras de butirato en el colon, a expensa de bacterias potencialmente dañinas como C. histolyticum. Además, los fitoquímicos son transformados por la MI en múltiples metabolitos que ejercen actividades biológicas a veces más potentes que la molécula inicial de la cual provienen. Individuos con distintos metabotipos han sido descritos de acuerdo a su capacidad de responder al consumo de isoflavonas, lignanos o elagitaninos, dependiendo de la presencia en su MI de bacterias capaces de transformar dichos polifenoles en equol, enterolactona/enterodiol y urolitinas, respectivamente, los cuales exhiben actividades biológicas. Valerolactonas y ácidos aromáticos también son producidos por la MI a través del metabolismo de las proantocianidinas. El efecto prebiótico de los fitoquímicos contribuiría a explicar los efectos saludables del consumo de frutas y verduras ricos en fitoquímicos.

ABSTRACT Intestinal microbiota (IM) is considered as a new target for the prevention and nutritional management of inflammatory and metabolic alterations associated with non-transmissible chronic diseases. Prebiotics are mainly soluble fibers whose consumption favors the growth of beneficial bacterial populations of the IM and positively impacts health. This review discusses dietary phytochemicals, which include more than 8,000 compounds, as a new class of prebiotics due to its ability to stimulate populations of Lactobacillus, Bifidobacterium, Akkermansia and butyrate producing bacteria in the colon at the expense of potentially harmful bacteria, such as C. histolyticum. In addition, phytochemicals are transformed by IM into a great array of metabolites exerting biological activities and are sometimes more potent than the initial molecule from which they are derived. Individuals with different metabotypes have been described according to their ability to respond to the consumption of isoflavones, lignans or ellagitannins, depending on the presence in their IM of bacteria capable of transforming these polyphenols into equol, enterolactone/enterodiol and urolithins, respectively, which exhibit biological activities. Valerolactones and aromatic acids are also produced by the IM through proanthocyanidin metabolism. The prebiotic effect of phytochemicals would help to explain the healthy effects associated with the consumption of fruits and vegetables rich in phytochemicals.

Protective Effect of an Avocado Peel Polyphenolic Extract Rich in Proanthocyanidins on the Alterations of Colonic Homeostasis Induced by a High-Protein Diet.

Avocado peel, a byproduct from the avocado pulp industry, is a promising source of polyphenolic compounds. We evaluated the effect of a proanthocyanidin-rich avocado peel polyphenol extract (AvPPE) on the composition and metabolic activity of human fecal microbiota cultured for 24 h in a bioreactor in the presence of high protein (HP) amounts and the effect of the resulting culture supernatants (CSs) on HT-29Glc-/+ and Caco-2 cells. AvPPE decreased the HP-induced production of ammonia, H2S, propionate, and isovalerate and increased that of indole and butyrate. Microbiota composition was marginally affected by HP, whileAvPPE increased the microorganisms/abundance of phylum Actinobacteria, families Coriobacteriaceae and Ruminococcaceae, and genus Faecalibacterium. AvPPE failed to prevent the HP-induced decrease of HT-29Glc-/+ cell viability and energy efficiency but prevented the HP-induced alterations of barrier function in Caco-2 cells. Additionally, the genotoxic effect of the CSs upon HT-29Glc-/+ was attenuated by AvPPE. Therefore, AvPPE may be considered as a promising product for improving colonic homeostasis.

Effect of a proanthocyanidin-rich polyphenol extract from avocado on the production of amino acid-derived bacterial metabolites and the microbiota composition in rats fed a high-protein diet.

The consumption of high-protein diets (HPDs) increases the flux of undigested proteins moving to the colon. These proteins are hydrolyzed by bacterial proteases and peptidases, releasing amino acids, which in turn are metabolized by the intestinal microbiota (IM) for protein synthesis and production of various metabolites that can exert positive or deleterious effects, depending on their concentrations, at the colonic or systemic level. On the other hand, proanthocyanidins are polymers of flavan-3-ols which cannot be absorbed at the intestinal level, accumulating in the colon where they are fermented by the IM producing metabolites that appear beneficial for colonocytes and also at the peripheral level. This study evaluated the effect of an avocado peel polyphenol extract (AvPPE) rich in proanthocyanidins on the production of cecal bacterial metabolites and microbiota composition in rats fed a HPD. Compared with the normal-protein (NP) group, HPD did not markedly affect the body weight gain of the animals, but increased the kidney weight. Additionally, the HPD induced a higher cecal concentration of ammonia (NH4+/NH3), hydrogen sulfide (H2S) and branched-chain fatty acids (BCFAs). The supplementation with AvPPE attenuated the production of H2S and increased the production of indole. On the other hand, the HPD affected the composition of the cecal microbiota, increasing the relative abundance of the genera Bacteroides and Lactobacillus, while decreasing Prevotella. The AvPPE counteracted the increase induced by the HPD on the genus Lactobacillus, and increased the relative abundance of [Prevotella]. Our results contribute towards explaining the health-promoting effects of proanthocyanidin-rich dietary foodstuffs including fruits and vegetables.

Quercetin and Epigallocatechin Gallate in the Prevention and Treatment of Obesity: From Molecular to Clinical Studies.

Obesity is a worldwide epidemic, which is characterized by the excess accumulation of adipose tissue and to an extent that impairs both the physical and psychosocial health and well-being. There are several weight-loss strategies available, including dietary modification, pharmacotherapy, and bariatric surgery, but many are ineffective or not a long-term solution. Bioactive compounds present in medicinal plants and plant extracts, like polyphenols, constitute the oldest and most extensive form of alternative treatments for the prevention and management of obesity. Their consumption is currently increasing in the population due to the high cost, potential adverse effects, and limited benefits of the currently available pharmaceutical drugs. A great number of studies has explored how dietary polyphenols can interfere with the different mechanisms associated with obesity development. They suggest that these compounds can decrease energy and food intake, lipogenesis, and preadipocyte differentiation and proliferation, while increasing energy expenditure, lipolysis, and fat oxidation. Both quercetin, one of the most common dietary flavonols in the western diet, and epigallocatechin gallate (EGCG), the most abundant polyphenol in green tea, exhibit antiobesity effects in adipocyte cultures and animal models. However, the extrapolation of these potential benefits to obese humans remains unclear. Although quercetin supplementation does not seem to exert any beneficial effects on body weight, this polyphenol could prevent the obesity-associated mortality by reducing cardiovascular disease risk. An important consideration for the design of further trials is the occurrence of gene polymorphisms in key enzymes involved in flavanol metabolism, which determines a subject's sensitivity to catechins and seems, therefore, crucial for the success of the antiobesity intervention. Although the evidence supporting antiobesity effects is more consistent in EGCG than with quercetin studies, they could still be beneficial by reducing the cardiovascular risk of obese subjects, rather than inducing body weight loss.