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.

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.

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.

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.

Proanthocyanidin-containing polyphenol extracts from fruits prevent the inhibitory effect of hydrogen sulfide on human colonocyte oxygen consumption.

Hydrogen sulfide (H2S), a metabolic end product synthesized by the microbiota from L-cysteine, has been shown to act at low micromolar concentration as a mineral oxidative substrate in colonocytes while acting as an inhibitor of oxygen consumption at higher luminal concentrations (65 µM and above). From the previous works showing that polyphenols can bind volatile sulfur compounds, we hypothesized that different dietary proanthocyanidin-containing polyphenol (PACs) plant extracts might modulate the inhibitory effect of H2S on colonocyte respiration. Using the model of human HT-29 Glc-/+ cell colonocytes, we show here that pre-incubation of 65 µM of the H2S donor NaHS with the different polyphenol extracts markedly reduced the inhibitory effect of NaHS on colonocyte oxygen consumption. Our studies on HT-29 Glc-/+ cell respiration performed in the absence or the presence of PACs reveal rapid binding of H2S with the sulfide-oxidizing unit and slower binding of H2S to the cytochrome c oxidase (complex IV of the respiratory chain). Despite acute inhibition of colonocyte respiration, no measurable effect of NaHS on paracellular permeability was recorded after 24 h treatment using the Caco-2 colonocyte monolayer model. The results are discussed in the context of the binding of excessive bacterial metabolites by unabsorbed dietary compounds and of the capacity of colonocytes to adapt to changing luminal environment.

3,4-Dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin, protects against pancreatic ß-cells dysfunction induced by high cholesterol.

Cholesterol plays an important role in inducing pancreatic ß-cell dysfunction, characterized by an impaired insulin secretory response to glucose, representing a hallmark of the transition from pre-diabetes to diabetes. 3,4 dihydroxyphenylacetic acid (ES) is a scarcely studied microbiota-derived metabolite of quercetin with antioxidant properties. The aim of this study was to determine the protective effect of ES against apoptosis, mitochondrial dysfunction and oxidative stress induced by cholesterol in Min6 pancreatic ß-cells. Cholesterol decreased viability, induced apoptosis and mitochondrial dysfunction by reducing complex I activity, mitochondrial membrane potential, ATP levels and oxygen consumption. Cholesterol promoted oxidative stress by increasing cellular and mitochondrial reactive oxygen species and lipid peroxidation and decreasing antioxidant enzyme activities; in addition, it slightly increased Nrf2 translocation to the nucleus. These events resulted in the impairment of the glucose-induced insulin secretion. ES increased Nrf2 translocation to the nucleus and protected pancreatic ß-cells against impaired insulin secretion induced by cholesterol by preventing oxidative stress, apoptosis and mitochondrial dysfunction. Nrf2 activation seems to be involved in the mechanisms underlying the antioxidant protection exerted by ES in addition to preventing the disruption of antioxidant enzymatic defenses. Although additional in vivo experiments are required, this metabolite is suggested as a promising drug target for the prevention of the pathological development from a pre-diabetic to a diabetic state.

The intake of maqui (Aristotelia chilensis) berry extract normalizes H2O2 and IL-6 concentrations in exhaled breath condensate from healthy smokers - an explorative study.

BACKGROUND: Respiratory diseases are associated with pulmonary oxidative stress and inflammatory processes. Though studies in animal models suggest that dietary polyphenols improve lung injury, no intervention studies were carried out in humans. The aim of this study was to determine whether the intake of an anthocyanin-rich maqui extract improved H2O2 and IL-6 concentrations in exhaled breath condensates (EBCs) from asymptomatic smokers. FINDINGS: 15 asymptomatic smokers with mild cigarette smoking (3 pack-year [2.4 - 7.7]) (mean [CI95%]) were recruited in this exploratory longitudinal study. They ingested 2 g of maqui extract (polyphenol content = 5.18 ± 2.00 g GAE/100 g; FRAP value = 27.1 ± 2.0 mmol Fe(++)/100 g), twice daily for two weeks. EBCs were collected before and after treatment and the changes in H2O2 and IL-6 concentrations were determined by fluorimetry and Elisa, respectively. The EBC contents of H2O2 and IL-6 H2O2 before and after treatment in smokers were also compared with those determined in single EBC samples from 8 healthy non-smokers subjects. At baseline, the H2O2 concentrations were higher and those of IL-6 lower in the smokers than in the non-smokers. Maqui extract significantly decreased H2O2 (p < 0.0002) and increased IL-6 (p < 0.004) in the EBC from smokers. The EBC concentrations of H2O2 and IL-6 after maqui administration did not differ between smokers and non-smokers. CONCLUSIONS: Maqui extract normalizes IL-6 and H2O2 concentrations in EBC from humans with mild smoking habits. If confirmed, these results suggest that dietary polyphenols might be considered as an interesting alternative for the dietary management of respiratory disorders.

Sucralose and stevia consumption leads to intergenerational alterations in body weight and intestinal expression of histone deacetylase 3.

OBJECTIVES: It is unclear whether parental consumption of non-nutritive sweetener (NNS) can affect subsequent generations. The aim of this study was to determine whether chronic parental consumption of sucralose and stevia in mice affects body weight gain and liver and intestinal expression of histone deacetylase 3 (Hdac3) in these animals and in the subsequent first filial (F1) and second filial (F2) generations. METHODS: Male and female mice (n = 47) were divided into three groups to receive water alone or supplemented with sucralose (0.1 mg/mL) or stevia (0.1 mg/mL) for 16 wk (parental [F0] generation). F0 mice were bred to produce the F1 generation; then, F1 mice were bred to produce the F2 generation. F1 and F2 animals did not receive NNSs. After euthanasia, hepatic and intestinal expression of Hdac3 was determined by quantitative reverse transcription polymerase chain reaction. RESULTS: Body weight gain did not differ between the three groups in the F0 generation, but it was greater in the F1 sucralose and stevia groups than in the control group. Consumption of both NNSs in the F0 generation was associated with lower Hdac3 expression in the liver and higher in the intestine. Hepatic Hdac3 expression was normalized to the control values in the F1 and F2 animals of the sucralose and stevia groups. Intestinal expression was still higher in the F1 generations of the sucralose and stevia groups but was partially normalized in the F2 generation of these groups, compared with control. CONCLUSIONS: NNS consumption differentially affects hepatic and intestinal Hdac3 expression. Changes in hepatic expression are not transmitted to the F1 and F2 generations whereas those in intestinal expression are enhanced in the F1 and attenuated in the F2 generations.

Nanoemulsions Based on Soluble Chenopodin/Alginate Complex for Colonic Delivery of Quercetin.

Inflammatory bowel disease (IBD) is an autoimmune disorder caused by uncontrolled immune activation and the subsequent destruction of the colon tissue. Quercetin (Qt) is a natural antioxidant and anti-inflammatory agent proposed as an alternative to mitigate IBD. However, its use is limited by its low oral bioavailability. This study aimed to develop nanoemulsions (NEs) based on a soluble chenopodin/alginate (QPA) complex and Tween 80 (T80), intended for the colonic release of Qt, activated by the pH (5.4) and bacteria present in the human colonic microbiota. NEs with different ratios of QPA/Tw80 (F1-F6) were prepared, where F4Qt (60/40) and F5Qt (70/30) showed sizes smaller than 260 nm, PDI < 0.27, and high encapsulation efficiency (>85%). The stability was evaluated under different conditions (time, temperature, pH, and NaCl). The DSC and FTIR analyses indicated hydrophobic and hydrogen bonding interactions between QPA and Qt. F4Qt and F5Qt showed the greater release of Qt in PBS1X and Krebs buffer at pH 5.4 (diseased condition), compared to the release at pH 7.4 (healthy condition) at 8 h of study. In the presence of E. coli and B. thetaiotaomicron, they triggered the more significant release of Qt (ƒ2 < 50) compared to the control (without bacteria). The NEs (without Qt) did not show cytotoxicity in HT-29 cells (cell viability > 80%) and increased the antioxidant capacity of encapsulated Qt. Therefore, these NEs are promising nanocarriers for the delivery of flavonoids to the colon to treat IBD.

Acute administration of Calafate (Berberis microphylla) extract induce the expression of thermogenic markers and modulates gut microbiota in mice fed a high-fat chow diet.

INTRODUCTION: Obesity, characterised by excess adipose tissue, is a major public health problem worldwide. Brown (BAT) and beige adipose tissue participate in thermogenesis through uncoupling protein 1 (UCP1). Polyphenols including those from Calafate (a native polyphenol-rich Patagonian berry), are considered as potential anti-obesity compounds due to their pro-thermogenic characteristics. However, polyphenols are mainly metabolized by the colonic microbiota by the gut microbiota (GM) that may influence their bioactivity and bioavailability. The aim of this study was to determine the impact of dietary administration with a Calafate polyphenol-rich extract on thermogenic activity of BAT and beige adipose tissue and GM composition. METHODS: 8-week-old C57BL6 mice (n=30) were divided into 4 groups to receive for 24 weeks a control diet (C), a high-fat diet alone (HF) or high-fat diet supplemented with Calafate extract (HFC) or the same high-fat diet supplemented with Calafate extract but treated with antibiotics (HFCAB) from week 19 to 20. Administration with Calafate extract (50 mg/kg. day) was carried out for 3 weeks from week 21 to 23 in the HFC and HFCAB groups. After euthanasia, gene expression of thermogenic markers was analysed in BAT and inguinal white adipose tissue (iWAT). Transmission electron microscopy was performed to assess mitochondrial morphology and cristae density in BAT. GM diversity and composition was characterized by deep sequencing with the MiSeq-Illumina platform. RESULTS: Calafate extract administration had no effect on weight gain in mice fed a high-fat diet. However, it prevented alterations in mitochondrial cristae induced by HFD, and increased Dio2 expression in BAT and iWAT. The intervention also influenced the gut microbiota composition, preventing changes in specific bacterial taxa induced by the high-fat diet. However, the antibiotic treatment prevented in part these effects, suggesting the implications of GM. DISCUSSION/CONCLUSION: These results suggest that the acute administration of a Calafate extract modulates the expression of thermogenic markers, prevents alterations in mitochondrial cristae and intestinal microbiota in preclinical models. The study highlights the complex interaction between polyphenols, thermogenesis and the gut microbiota, providing valuable insights into their potential roles in the treatment of obesity-related metabolic diseases.

Stimulation of cytosolic and mitochondrial calcium mobilization by indomethacin in Caco-2 cells: modulation by the polyphenols quercetin, resveratrol and rutin.

BACKGROUND: The effect of indomethacin (INDO) on Ca(2+) mobilization, cytotoxicity, apoptosis and caspase activation and the potential protective effect of quercetin (QUE), resveratrol (RES) and rutin (RUT) were determined in Caco-2 cells. METHODS: Caco-2 cells were incubated with INDO in the presence or absence of QUE, RES or RUT. The concentrations of Ca(2+) in the cytosol (Fluo-3 AM) and mitochondria (Rhod-2 AM) were determined as well as the cytotoxicity (MTT reduction and LDH leakage), apoptosis (TUNEL) and caspase-3 and 9 activities. RESULTS: INDO promoted Ca(2+) efflux from the endoplasmic reticulum (ER), resulting in an early, but transient, increment of cytosolic Ca(2+) at 3.5min, followed by a subsequent increment of intra-mitochondrial Ca(2+) at 24min. INDO also induced cytotoxicity, apoptosis, and increased caspase activities and cytochrome c release. All these alterations were prevented by the inhibitors of the IP3R and RyR receptors, 2-Aminoethoxydiphenyl borate (2-APB) and dantrolene. QUE was the most efficient polyphenol in preventing Ca(2+) mobilization induced by INDO and all of its consequences including cytotoxicity and apoptosis. CONCLUSIONS: In Caco-2 cells, INDO stimulates ER Ca(2+) mobilization, probably through the activation of IP3R and RyR receptors, and the subsequent entry of Ca(2+) into the mitochondria. Polyphenols protected the cells against the Ca(2+) mobilization induced by INDO and its consequences on cytotoxicity and apoptosis. GENERAL SIGNIFICANCE: These results confirm the possibility of using polyphenols and particularly QUE for the protection of the gastroduodenal mucosa in subjects consuming NSAIDs.

Re-print of "Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host".

Alimentary and endogenous proteins are mixed in the small intestinal lumen with the microbiota. Although experimental evidences suggest that the intestinal microbiota is able to incorporate and degrade some of the available amino acids, it appears that the microbiota is also able to synthesize amino acids raising the view that amino acid exchange between the microbiota and host can proceed in both directions. Although the net result of such exchanges remains to be determined, it is likely that a significant part of the amino acids recovered from the alimentary proteins are used by the microbiota. In the large intestine, where the density of bacteria is much higher than in the small intestine and the transit time much longer, the residual undigested luminal proteins and peptides can be degraded in amino acids by the microbiota. These amino acids cannot be absorbed to a significant extent by the colonic epithelium, but are precursors for the synthesis of numerous metabolic end products in reactions made by the microbiota. Among these products, some like short-chain fatty acids and organic acids are energy substrates for the colonic mucosa and several peripheral tissues while others like sulfide and ammonia can affect the energy metabolism of colonic epithelial cells. More work is needed to clarify the overall effects of the intestinal microbiota on nitrogenous compound metabolism and consequences on gut and more generally host health.

Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host.

Alimentary and endogenous proteins are mixed in the small intestinal lumen with the microbiota. Although experimental evidences suggest that the intestinal microbiota is able to incorporate and degrade some of the available amino acids, it appears that the microbiota is also able to synthesize amino acids raising the view that amino acid exchange between the microbiota and host can proceed in both directions. Although the net result of such exchanges remains to be determined, it is likely that a significant part of the amino acids recovered from the alimentary proteins are used by the microbiota. In the large intestine, where the density of bacteria is much higher than in the small intestine and the transit time much longer, the residual undigested luminal proteins and peptides can be degraded in amino acids by the microbiota. These amino acids cannot be absorbed to a significant extent by the colonic epithelium, but are precursors for the synthesis of numerous metabolic end products in reactions made by the microbiota. Among these products, some like short-chain fatty acids and organic acids are energy substrates for the colonic mucosa and several peripheral tissues while others like sulfide and ammonia can affect the energy metabolism of colonic epithelial cells. More work is needed to clarify the overall effects of the intestinal microbiota on nitrogenous compound metabolism and consequences on gut and more generally host health.

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.

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.

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.

Increase of plasma fatty acids without changes in n-6/n-3-PUFA ratio in asymptomatic obese subjects.

Obesity is associated with a low grade inflammation which contributes to the development of insulin resistance and diabetes. The aim of this study was to assess the total saturated (SFAs), monounsaturated (MUFAs) and polyunsaturated fatty acids (PUFAs) in plasma from asymptomatic obese subjects and to determine the arachidonic/eicosapentanoic acid ratio [ARA/EPA] as a marker of inflammation, and its eventual association with ultrasensitive CRP. Fourteen obese (34.4 +/- 11.1y.; BMI: 36.0 +/- 4,5 kg/m2) and 12 normal-weight (30.6 +/- 7.8y.; BMI: 23,6 +/- 2,4 kg/m2) subjects were recruited and their plasma fatty acids were determined by gas chromatography. usCRP was higher in the obese subjects (p = 0.01) and correlates with their body fat content. The percentages of SFAs, MUFAs, PUFAs were not affected in the obese subjects but their concentrations were increased, compared with the control group. However, no differences in the long chain PUFAs (DHA and EPA) concentrations or in the plasmatic ARA/EPA ratio were observed in these subjects. These observations do not support a relation between the ARA/EPA ratio and the presence of low grade inflammation evaluated by plasma usCRP in this group of asymptomatic obese subjects.

Identification of Lactobacillus spp. in colostrum from Chilean mothers.

The biodiversity of Lactobacillus spp. in colostrum samples from 116 Chilean mothers was analyzed by PCR and 16S rDNA sequencing. Lactobacilli were isolated in 55.3% of the samples, with concentrations of 3.33 +/- 0.55 (log CFU/ml). The predominant species were L. plantarum (64%), L. fermentum (16%) and L. pentosus (9%). 28% of the isolated strains were resistant to gastric pH and bile salts, suggesting that they could be used as probiotics.