Epidemiological studies have shown an inverse association between dietary intake of whole grains and the risk of chronic disease. This may be related to the ability to mediate a prebiotic modulation ...of gut microbiota. However, no studies have been conducted on the microbiota modulatory capability of whole-grain (WG) cereals. In the present study, the impact of WG wheat on the human intestinal microbiota compared to wheat bran (WB) was determined. A double-blind, randomised, crossover study was carried out in thirty-one volunteers who were randomised into two groups and consumed daily 48 g breakfast cereals, either WG or WB, in two 3-week study periods, separated by a 2-week washout period. Numbers of faecal bifidobacteria and lactobacilli (the target genera for prebiotic intake), were significantly higher upon WG ingestion compared with WB. Ingestion of both breakfast cereals resulted in a significant increase in ferulic acid concentrations in blood but no discernible difference in faeces or urine. No significant differences in faecal SCFA, fasting blood glucose, insulin, total cholesterol (TC), TAG or HDL-cholesterol were observed upon ingestion of WG compared with WB. However, a significant reduction in TC was observed in volunteers in the top quartile of TC concentrations upon ingestion of either cereal. No adverse intestinal symptoms were reported and WB ingestion increased stool frequency. Daily consumption of WG wheat exerted a pronounced prebiotic effect on the human gut microbiota composition. This prebiotic activity may contribute towards the beneficial physiological effects of WG wheat.
Wheat bran fibers are considered beneficial to human health through their impact on gut microbiota composition and activity. Here, we assessed the prebiotic potential of selected bran fractions by ...performing a series of fecal slurry anaerobic fermentation experiments using aleurone as well as total, ultrafine, and soluble wheat bran (swb) as carbon sources. By combining amplicon-based community profiling with a fluorescent
hybridization (FISH) approach, we found that incubation conditions favor the growth of Proteobacteria such as
and
. These effects were countered in all but one total wheat bran (twb) fermentation experiments. Growth of
species was stimulated after fermentation using ultrafine, soluble, and twb, in the latter two as part of a general increase in bacterial load. Both ultrafine and swb fermentation resulted in a trade-off between
and
, as previously observed in human dietary supplementation studies looking at the effect of inulin-type fructans on the human gut microbiota. Aleurone selectively stimulated growth of
and butyrate-producing
. All fermentation experiments induced enhanced gas production; increased butyrate concentrations were only observed following soluble bran incubation. Our results open perspectives for the development of aleurone as a complementary prebiotic selectively targeting colon butyrate producers.
Heat-processed diets contain high amounts of advanced glycation end products (AGEs). Here we explore the impact of an AGE-enriched diet on markers of metabolic and inflammatory disorders as well as ...on gut microbiota composition and plasma proteins glycosylation pattern. C57BL/6 mice were allocated into control diet (CD,
= 15) and AGE-enriched diet (AGE-D,
= 15) for 22 weeks. AGE-D was prepared replacing casein by methylglyoxal hydroimidazolone-modified casein. AGE-D evoked increased insulin and a significant reduction of GIP/GLP-1 incretins and ghrelin plasma levels, altered glucose tolerance, and impaired insulin signaling transduction in the skeletal muscle. Moreover, AGE-D modified the systemic glycosylation profile, as analyzed by lectin microarray, and increased Nε-carboxymethyllysine immunoreactivity and AGEs receptor levels in ileum and submandibular glands. These effects were associated to increased systemic levels of cytokines and impaired gut microbial composition and homeostasis. Significant correlations were recorded between changes in bacterial population and in incretins and inflammatory markers levels. Overall, our data indicates that chronic exposure to dietary AGEs lead to a significant unbalance in incretins axis, markers of metabolic inflammation, and a reshape of both the intestinal microbiota and plasma protein glycosylation profile, suggesting intriguing pathological mechanisms underlying AGEs-induced metabolic derangements.
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•Wolffia globosa an emerging functional food, targets obesity and metabolic disease.•Wolffia globosa rich in fiber and polyphenols modulates the gut microbiome.•Wolffia globosa ...increases microbiota phenolic acid and SCFA production in vitro.•Microbiome modulation may underpin certain health effects of Wolffia globosa ingestion.
Mankai® is a cultivated strain of Wolffia globosa an aquatic plant of the family Lemnaceae commonly known as Duckweeds. Recent studies suggest that consumption of a Mankai® enriched diet may provide positive health effects by decreasing body weight and improving glucose homeostasis and plasma lipid profiles. However, the effects of Mankai® alone on the composition and metabolic output of the human gut microbiota has not been fully investigated. Here, Mankai® was digested and fermented in vitro using a batch culture model of the proximal colon. Inulin and cellulose were used as readily and poorly fermentable control fibers respectively. Mankai® significantly stimulated the production of phenolic metabolites and short chain fatty acids by the gut microbiota (p<0.05). Three major microbial metabolites, 3-4-hydroxyphenyl propionic acid, 3-3-hydroxyphenyl propanoic acid and protocatechuic acid were significantly increased after 24 h fermentation. Moreover, Mankai® treatment lowered the overall microbial diversity (p<0.05), in line with a selective microbiome modulation.
Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, ...infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807G > A; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratio = 2.27, 95% Confidence Interval 1.54-3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53-3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Q ≥ 23 in the androgen receptor (OR 3.26, 95% CI 1.41-7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor.
Sauerkraut is a traditionally fermented cabbage, and recent evidence suggests that it has beneficial properties for human health. In this work, a multi-disciplinary approach was employed to ...characterize the fermentation process and gut health-promoting properties of locally produced, organic sauerkraut from two distinct producers, SK1 and SK2. 16S rRNA metataxonomics showed that bacterial diversity gradually decreased as fermentation progressed. Differences in sauerkraut microbiota composition were observed between the two producers, especially at the start of fermentation. Lactic acid bacteria (LAB) dominated the microbiota after 35 days, with
Lactiplantibacillus
being the dominant genus in both sauerkraut products, together with
Leuconostoc
and
Paucilactobacillus
in SK1, and with
Pediococcus, Levilactibacillus
, and
Leuconostoc
in SK2. LAB reached between 7 and 8 Log CFU/mL brine at the end of fermentation (35 days), while pH lowering happened within the first week of fermentation. A total of 220 LAB strains, corresponding to 133 RAPD-PCR biotypes, were successfully isolated.
Lactiplantibacillus plantarum
and
Lactiplantibacillus pentosus
accounted for 67% of all SK1 isolates, and
Lactiplantibacillus plantarum/paraplantarum
and
Leuconostoc mesenteroides
represented 72% of all the isolates from SK2.
1
H-NMR analysis revealed significant changes in microbial metabolite profiles during the fermentation process, with lactic and acetic acids, as well as amino acids, amines, and uracil, being the dominant metabolites quantified. Sauerkraut brine did not affect trans-epithelial electrical resistance through a Caco-2 cell monolayer as a measure of gut barrier function. However, significant modulation of inflammatory response after LPS stimulation was observed in PBMCs-Caco-2 co-culture. Sauerkraut brine supported a robust inflammatory response to endotoxin, by increasing TNF-α and IL-6 production while also stimulating the anti-inflammatory IL-10, therefore suggesting positive resolution of inflammation after 24 h and supporting the potential of sauerkraut brine to regulate intestinal immune function.
During the last two decades incidences of fungal infections dramatically increased and the often accompanying failure of available antifungal therapies represents a substantial clinical problem. The ...urgent need for novel antimycotics called particular attention to the study of natural products. The genus
includes many species that are used in the traditional medicine to treat pathological states like inflammations and infections caused by fungi. However, despite the diffused use of
-based products the antifungal potential of the genus is still poorly investigated. In this study five
species autochthonous of Central and Eastern Europe were evaluated regarding their polyphenolic content, their toxicological safety and their antifungal potential against a broad panel of clinical fungal isolates. LC-MS analysis led to the identification and quantification of 52 compounds, revealing that
extracts are rich sources of flavonols, benzoates and cinnamates, and of flavan-3-ols. An in-depth screen of the biological activity of crude extracts clearly unveiled
subsp.
as a promising candidate species for the search of novel antifungals.
is diffused in the Mediterranean basin from Spain to Turkey where it is traditionally used to prepare a herbal tea indicated for the treatment of respiratory tract disorders, several of which are caused by fungi. Noteworthy, the infusion of
subsp.
excreted broad antifungal activity against
and non
isolates comprising strains both sensitive and resistant to fluconazole. Additionally, it showed no cytotoxicity on human cells and the chemical characterization of the
subsp.
infusion revealed high amounts of the metabolite hyperoside. These results scientifically support the traditional use of
extracts for the treatment of respiratory tract infections and suggest the presence of exploitable antifungal principles for further investigations aimed at developing novel antifungal therapies.
Recent evidence suggests the substantial pathogenic role of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in the development of low-grade chronic inflammatory ...response, known as “metaflammation,” which contributes to obesity and type 2 diabetes. In this study, we investigated the effects of the JAK1/2 inhibitor baricitinib, recently approved for the treatment of rheumatoid arthritis, in a murine high-fat-high sugar diet model.
Male C57BL/6 mice were fed with a control normal diet (ND) or a high-fat-high sugar diet (HD) for 22 weeks. A sub-group of HD fed mice was treated with baricitinib (10 mg/kg die, p.o.) for the last 16 weeks (HD + Bar).
HD feeding resulted in obesity, insulin-resistance, hypercholesterolemia and alterations in gut microbial composition. The metabolic abnormalities were dramatically reduced by chronic baricitinib administration. Treatment of HD mice with baricitinib did not change the diet-induced alterations in the gut, but restored insulin signaling in the liver and skeletal muscle, resulting in improvements of diet-induced myosteatosis, mesangial expansion and associated proteinuria. The skeletal muscle and renal protection were due to inhibition of the local JAK2-STAT2 pathway by baricitinib. We also demonstrated that restored tissue levels of JAK2-STAT2 activity were associated with a significant reduction in cytokine levels in the blood.
In summary, our data suggest that the JAK2-STAT2 pathway may represent a novel candidate for the treatment of diet-related metabolic derangements, with the potential for EMA- and FDA-approved JAK inhibitors to be repurposed for the treatment of type 2 diabetes and/or its complications.
•The Jak/Stat signaling pathway is dysregulated in metabolic diseases.•The Jak2 inhibitor baricitinib exerts multi-organ protection against diet-induced metabolic derangements.•Targeting the chronic metabolic inflammation (termed metaflammation) represents an effective strategy for metabolic diseases.
•Increase in relative abundances of beneficial gut microbes observed for SDB and BYB.•Acetate and butyrate levels were higher for SDB after 24-h faecal fermentation.•Inflammatory cytokines were ...downregulated by SDB fermentation supernatants.•Spontaneous sourdough fermentation influences gut health at the metabolite level.
Spontaneous fermentation of Tritordeum flour enhances the nutritional potential of this hybrid cereal. However, the effect of consumption of Tritordeum sourdough bread (SDB) on gut health remains to be elucidated. This study investigated the effect of in vitro digestion and faecal fermentation of SDB compared to that of traditional baker's yeast (BYB) Tritordeum bread. After 24-h anaerobic faecal fermentation, both SDB and BYB (1% w/v) induced an increase in the relative abundances of Bifidobacterium, Megasphaera, Mitsuokella, and Phascolarctobacterium genera compared to baseline, while concentrations of acetate and butyrate were significantly higher at 24 h for SDB compared to those for BYB. Integrity of intestinal epithelium, as assessed through in vitro trans-epithelial electrical resistance (TEER) assay, was slightly increased after incubation with SDB fermentation supernatants, but not after incubation with BYB fermentation supernatants. The SDB stimulated in vitro mucosal immune response by inducing early secretion of inflammatory cytokines, IL-6 and TNF-α, followed by downregulation of the inflammatory trigger through induction of anti-inflammatory IL-10 expression. Overall, our findings suggest that Tritordeum sourdough can modulate gut microbiota fermentation activity and positively impact the gut health.
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