Search Results (18)

Background/Objectives: Gut microbiota is essential for maintaining host immune homeostasis and has been confirmed to be closely related to some intestinal and extraintestinal diseases. Bacteroides, as the dominant bacterial genus in the human gut, has attracted great attention due to its excellent metabolic activity, but there are few studies on Bacteroides dorei species. In our previous study, a gut commensal strain, Bacteroides dorei RX2020 (B. dorei), was isolated from healthy human feces and exhibited superior flavonoid metabolic activity, prompting further analysis of its uncharacterized genomic features, probiotic potential, safety, and immunomodulatory activity. Results: The results showed that B. dorei exhibited intrinsic probiotic functionalities with preserved genomic and phenotypic stability, demonstrated safety profiles in murine models through in vivo assessments, and conferred antagonistic activity against enteric foodborne pathogens via competitive exclusion. The strain also demonstrated abundant metabolic activity and was involved in the metabolism of tryptophan and bile acids (BAs). Moreover, B. dorei can promote the production of IFNβ by dendritic cells (DCs) to inhibit the replication of influenza virus in epithelial cells, which may be achieved by regulating host metabolism. Conclusions: This study reveals the potential of B. dorei as next-generation probiotics (NGPs), contributing to a broader understanding and application of these novel probiotics in health and disease management. Full article

The present study evaluates the effects of açai juice containing gluco-oligosaccharides and dextran, fermented by Bifidobacterium breve NRRL B-41408 (synbiotic juice), on the human fecal microbiota. The juice is subjected to simulated digestion and fecal fermentation after production and 42 days of refrigerated storage. High throughput 16S rRNA sequencing and HPLC are used to identify the bacterial cells and metabolites. The results show that the viability of B. breve is stable during the refrigerated storage, indicating that the metabolism is maintained even under low temperatures and pH. Furthermore, gluco-oligosaccharides and dextran prove to be resistant to gastrointestinal conditions and are quickly consumed during fecal fermentation. The synbiotic açai juice enhances the microbial diversity and stimulates the production of short-chain fatty acids (SCFA), including acetate, propionate, and isobutyrate. Elevated propionate levels are directly associated with an increased abundance of Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides xylanisolvens, Bacteroides dorei, Bacteroides stercoris, and Bacteroides massiliensis after 48 h of fermentation. This highlights the potential of synbiotic açai juice as a functional beverage, supported by the significant increase in microbial diversity reflected in the Shannon and Simpson’s diversity indexes (Shannon = 116.6%, 117.2%, 125.15%, and 116.02%; Simpson’s = 151.86%, 177.22%, 152.5%, and 163.73%). Full article

GoodBiome™ Foods are functional foods containing a probiotic (Bacillus subtilis HU58™) and prebiotics (mainly inulin). Their effects on the human gut microbiota were assessed using ex vivo SIFR^® technology, which has been validated to provide clinically predictive insights. GoodBiome™ Foods (BBM/LCM/OSM) were subjected to oral, gastric, and small intestinal digestion/absorption, after which their impact on the gut microbiome of four adults was assessed (n = 3). All GoodBiome™ Foods boosted health-related SCFA acetate (+13.1/14.1/13.8 mM for BBM/LCM/OSM), propionate (particularly OSM; +7.4/7.5/8.9 mM for BBM/LCM/OSM) and butyrate (particularly BBM; +2.6/2.1/1.4 mM for BBM/LCM/OSM). This is related to the increase in Bifidobacterium species (B. catenulatum, B. adolescentis, B. pseudocatenulatum), Coprococcus catus and Bacteroidetes members (Bacteroides caccae, Phocaeicola dorei, P. massiliensis), likely mediated via inulin. Further, the potent propionogenic potential of OSM related to increased Bacteroidetes members known to ferment oats (s key ingredient of OSM), while the butyrogenic potential of BBM related to a specific increase in Anaerobutyricum hallii, a butyrate producer specialized in the fermentation of erythritol (key ingredient of BBM). In addition, OSM/BBM suppressed the pathogen Clostridioides difficile, potentially due to inclusion of HU58™ in GoodBiome™ Foods. Finally, all products enhanced a spectrum of metabolites well beyond SCFA, including vitamins (B3/B6), essential amino acids, and health-related metabolites such as indole-3-propionic acid. Overall, the addition of specific ingredients to complex foods was shown to specifically modulate the gut microbiome, potentially contributing to health benefits. Noticeably, our findings contradict a recent in vitro study, underscoring the critical role of employing a physiologically relevant digestion/absorption procedure for a more accurate evaluation of the microbiome-modulating potential of complex foods. Full article

The impact of prebiotics on human health is associated with their capacity to modulate microbiota, improving beneficial microbiota–host interactions. Herein, the prebiotic potential of microbial-fructo-oligosaccharides (microbial-FOSs) produced by a co-culture of Aspergillus ibericus plus Saccharomyces cerevisiae was evaluated on seven- and nine-strain bacterial consortia (7SC and 9SC, respectively), designed to represent the human gut microbiota. The 7SC was composed of Bacteroides dorei, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Escherichia coli, Lactobacillus acidophilus, and Lactobacillus rhamnosus. The 9SC also comprised the aforementioned bacteria, with the addition of Bacteroides thetaiotaomicron and Roseburia faecis. The effect of microbial-FOSs on the metabolic activity of intestinal Caco-2/HT29-MTX-E12 co-culture was also assessed. The results showed that microbial-FOS selectively promoted the growth of probiotic bacteria and completely suppressed the growth of E. coli. The microbial-FOSs promoted the highest production rates of lactate and total short-chain fatty acids (SCFA) as compared to the commercial prebiotic Frutalose^® OFP. Butyrate was only produced in the 9SC consortium, which included the R. faecis—a butyrate-producing bacteria. The inclusion of this bacteria plus another Bacteroides in the 9SC promoted a greater metabolic activity in the Caco-2/HT29-MTX-E12 co-culture. The microbial-FOSs showed potential as promising prebiotics as they selectively promote the growth of probiotic bacteria, producing high concentrations of SCFA, and stimulating the metabolic activity of gut cells. Full article

Gut microbiota has been described as a new ‘organ’ that interferes with host physiology by its metabolites produced from the utilization and biotransformation of undigested food components. Fu Ling (FL), the sclerotia of fungi Wolfiporia cocos, contains β-glucan, which is a known natural polysaccharide with strong medicinal efficacy. This study endeavors to evaluate the fermentability of FL and polysaccharides extracted from its sclerotia. An in vitro fermentation of structurally characterized FL and its β-glucan by human fecal microbiota was conducted. Total bacterial count, pH change, short-chain fatty acid profile and microbiota profile were assessed post-fermentation. FL containing over 70% of β-(1 → 3) and (1 → 6)-glucans with a low degree of branching of 0.24 could enhance acetic acid (a major microbial metabolite) production. Both FL and its extracted β-glucan had similar modulation on microbial composition. They enriched Phascolarctobacterium faecium, Bacteroides dorei and Parabacteroides distasonis, all of which are shown to possess anti-inflammatory effects. FL polysaccharide can be utilized as a natural whole food for its potential health benefits to human gut bacteria. Full article

This study aims to combine computed tomography (CT)-based texture analysis (QTA) and a microbiome-based biomarker signature to predict the overall survival (OS) of immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients by analyzing their CT scans (n = 129) and fecal microbiome (n = 58). One hundred and five continuous CT parameters were obtained, where principal component analysis (PCA) identified seven major components that explained 80% of the data variation. Shotgun metagenomics (MG) and ITS analysis were performed to reveal the abundance of bacterial and fungal species. The relative abundance of Bacteroides dorei and Parabacteroides distasonis was associated with long OS (>6 mo), whereas the bacteria Clostridium perfringens and Enterococcus faecium and the fungal taxa Cortinarius davemallochii, Helotiales, Chaetosphaeriales, and Tremellomycetes were associated with short OS (≤6 mo). Hymenoscyphus immutabilis and Clavulinopsis fusiformis were more abundant in patients with high (≥50%) PD-L1-expressing tumors, whereas Thelephoraceae and Lachnospiraceae bacterium were enriched in patients with ICI-related toxicities. An artificial intelligence (AI) approach based on extreme gradient boosting evaluated the associations between the outcomes and various clinicopathological parameters. AI identified MG signatures for patients with a favorable ICI response and high PD-L1 expression, with 84% and 79% accuracy, respectively. The combination of QTA parameters and MG had a positive predictive value of 90% for both therapeutic response and OS. According to our hypothesis, the QTA parameters and gut microbiome signatures can predict OS, the response to therapy, the PD-L1 expression, and toxicity in NSCLC patients treated with ICI, and a machine learning approach can combine these variables to create a reliable predictive model, as we suggest in this research. Full article

The pharmacokinetic variability of nifedipine widely observed in the clinic cannot be fully explained by pharmacogenomics. As a new factor affecting drug metabolism, how the gut microbiota affects the pharmacokinetics of nifedipine needs to be explored. Spontaneously hypertensive rats (SHRs) have been commonly used in hypertension-related research and served as the experimental groups; Wistar rats were used as control groups. In this study, the bioavailability of nifedipine decreased by 18.62% (p < 0.05) in the SHRs compared with the Wistar rats. Changes in microbiota were associated with the difference in pharmacokinetics. The relative abundance of Bacteroides dorei was negatively correlated with AUC_0–t (r = −0.881, p = 0.004) and C_max (r = −0.714, p = 0.047). Analysis of serum bile acid (BA) profiles indicated that glycoursodeoxycholic acid (GUDCA) and glycochenodeoxycholic acid (GCDCA) were significantly increased in the SHRs. Compared with the Wistar rats, the expressions of CYP3A1 and PXR were upregulated and the enzyme activity of CYP3A1 increased in the SHRs. Spearman’s rank correlation revealed that Bacteroides stercoris was negatively correlated with GUDCA (r = −0.7126, p = 0.0264) and GCDCA (r = −0.6878, p = 0.0339). Moreover, GUDCA was negatively correlated with C_max (r = −0.556, p = 0.025). In primary rat hepatocytes, GUDCA could induce the expressions of PXR target genes CYP3A1 and Mdr1a. Furthermore, antibiotic treatments in SHRs verified the impact of microbiota on the pharmacokinetics of nifedipine. Generally, gut microbiota affects the pharmacokinetics of nifedipine through microbial biotransformation or by regulating the enzyme activity of CYP3A1. Full article

The human gut microbiota is characterized by large interpersonal differences, which are not only linked to health and disease but also determine the outcome of nutritional interventions. In line with the growing interest for developing targeted gut microbiota modulators, the selectivity of a carrot-derived rhamnogalacturonan I (cRG-I) was compared to substrates with demonstrated low (inulin, IN) and high selectivity (xanthan, XA), at a human equivalent dose (HED) of 1.5 g/d. The high throughput of the ex vivo SIFR^® technology, validated to generate predictive insights for clinical findings, enabled the inclusion of 24 human adults. Such an unprecedented high number of samples in the context of in vitro gut microbiota modelling allowed a coverage of clinically relevant interpersonal differences in gut microbiota composition and function. A key finding was that cRG-I supplementation (already at an HED of 0.3 g/d) lowered interpersonal compositional differences due to the selective stimulation of taxa that were consistently present among human adults, including OTUs related to Bacteroides dorei/vulgatus and Bifidobacterium longum (suspected keystone species), Bacteroides thetaiotaomicron, Bifidobacterium adolescentis and butyrate-producing taxa such as Blautia sp., Anaerobutyricum hallii, and Faecalibacterium prausnitzii. In contrast, both IN and XA treatments increased interpersonal compositional differences. For IN, this followed from its low specificity. For XA, it was rather the extremely high selectivity of XA fermentation that caused large differences between 15 responders and 9 nonresponders, caused by the presence/absence of highly specific XA-fermenting taxa. While all test compounds significantly enhanced acetate, propionate, butyrate, and gas production, cRG-I resulted in a significantly higher acetate (+40%), propionate (+22%), yet a lower gas production (–44%) compared to IN. cRG-I could thus result in overall more robust beneficial effects, while also being better tolerated. Moreover, owing to its remarkable homogenization effect on microbial composition and metabolite production, cRG-I could lead to more predictable outcomes compared to substrates that are less specific or overly specific. Full article

Extended-spectrum β-lactamases confer resistance to a variety of β-lactam antimicrobials, and the genes for these enzymes are often found on plasmids that include additional antimicrobial resistance genes (ARG). We surveyed aquatic environments in the Indiana Lake Michigan watershed in proximity to areas with high densities of residential septic systems to determine if human fecal contamination from septic effluent correlated with the presence of antimicrobial resistance genes and phenotypically resistant bacteria. Of the 269 E. coli isolated from environmental samples and one septic source, 97 isolates were resistant to cefotaxime, a third-generation cephalosporin. A subset of those isolates showed phenotypic resistance to other β-lactams, fluoroquinolones, sulfonamides, and tetracyclines. Quantitative PCR was used to quantify human-associated Bacteroides dorei gene copies (Human Bacteroides) from water samples and to identify the presence of ARG harbored on plasmids from E. coli isolates or in environmental DNA. We found a strong correlation between the presence of ARG and human fecal concentrations, which supports our hypothesis that septic effluent is a source of ARG and resistant organisms. The observed plasmid-based resistance adds an additional level of risk, as human-associated bacteria from septic systems may expand the environmental resistome by acting as a reservoir of transmissible resistance genes. Full article

Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation. Full article

Intestinal dysbiosis is a key feature in the pathogenesis of inflammatory bowel disease (IBD). Acyl-homoserine lactones (AHL) are bacterial quorum-sensing metabolites that may play a role in the changes in host cells-gut microbiota interaction observed during IBD. The objective of our study was to investigate the presence and expression of AHL synthases and receptor genes in the human gut ecosystem during IBD. We used an in silico approach, applied to the Inflammatory Bowel Disease Multi’omics Database comprising bacterial metagenomic and metatranscriptomic data from stools of patients with Crohn’s disease (CD) (n = 50), ulcerative colitis (UC) (n = 27) and non-IBD controls (n = 26). No known putative AHL synthase gene was identified; however, several putative luxR receptors were observed. Regarding the expression of these receptor genes, the luxR gene from Bacteroides dorei was under-expressed in IBD patients (p = 0.02) compared to non-IBD patients, especially in CD patients (p = 0.02). In the dysbiosis situation, one luxR receptor gene from Bacteroides fragilis appeared to be over-expressed (p = 0.04) compared to that of non-dysbiotic patients. Targeting LuxR receptors of bacterial quorum sensing might represent a new approach to modulate the gut microbiota in IBD. Full article

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell’s stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3–V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results. Full article

The human gut microbiome is currently recognized to play a vital role in human biology and development, with diet as a major modulator. Therefore, novel indigestible polysaccharides that confer a health benefit upon their fermentation by the microbiome are under investigation. Based on the recently demonstrated prebiotic potential of a carrot-derived pectin extract enriched for rhamnogalacturonan I (cRG-I), the current study aimed to assess the impact of cRG-I upon repeated administration using the M-SHIME technology (3 weeks at 3g cRG-I/d). Consistent effects across four simulated adult donors included enhanced levels of acetate (+21.1 mM), propionate (+17.6 mM), and to a lesser extent butyrate (+4.1 mM), coinciding with a marked increase of OTUs related to Bacteroides dorei and Prevotella species with versatile enzymatic potential likely allowing them to serve as primary degraders of cRG-I. These Bacteroidetes members are able to produce succinate, explaining the consistent increase of an OTU related to the succinate-converting Phascolarctobacterium faecium (+0.47 log₁₀(cells/mL)). While the Bifidobacteriaceae family remained unaffected, a specific OTU related to Bifidobacterium longum increased significantly upon cRG-I treatment (+1.32 log₁₀(cells/mL)). Additional monoculture experiments suggested that Bifidobacterium species are unable to ferment cRG-I structures as such and that B. longum probably feeds on arabinan and galactan side chains of cRG-I, released by aforementioned Bacteroidetes members. Overall, this study confirms the prebiotic potential of cRG-I and additionally highlights the marked consistency of the microbial changes observed across simulated subjects, suggesting the involvement of a specialized consortium in cRG-I fermentation by the human gut microbiome. Full article

In our previous study the enrichment of the intestinal proteome of type 1 diabetes (T1D) children with Bacteroides proteins was observed, which led us to our current study that aimed to isolate and characterize Bacteroides species from fecal samples of T1D and control children. Repetitive sequence-based PCR (rep-PCR) was used for typing the isolated Bacteroides species. The antibiotic susceptibility and mucinolytic activity of the isolates was determined. The quantification of specific bacterial groups in the fecal samples was determined by qPCR. The ability to adhere and invade the human colonic cell line HT29-MTX-E12 of strains of P. dorei, B. uniformis and P. distasonis was determined and their whole genome sequencing was performed. The results showed similar numbers of Bacteroides species in T1D and control samples, but unique Bacteroides species and a higher recovery of P. distasonis from T1D samples was observed. Rep-PCR grouped the different Bacteroides species, but no discrimination by origin was achieved. T1D children showed a significant increase in Proteobacteria and a depletion in Lactobacillus sp. All tested P. dorei, B. uniformis and P. distasonis were able to adhere to HT29-MTX-E12 cells but significant differences (p < 0.05) in the ability to invade was observed. The highest ability to invade was exhibited by P. distasonis PtF D14MH1 and P. dorei PtFD16P1, while B. uniformis strains were unable to invade. The damage to tight junctions was also observed. The presence of Lactobacillus sp. inhibited the invasion ability of P. distasonis PtF D14MH1 but not P. dorei PtFD16P1. Sequences of agonist peptides of the human natural preproinsulin and the insulin B chain insB:9-23 peptide mimics were identified. The results reported in our study stresses the continued efforts required to clarify the link between T1D and gut microbiota. Full article

Background: Gut microbiota metabolize select dietary (poly)phenols to absorbable metabolites that exert biological effects important in metabolic health. Microbiota composition associated with health/disease status may affect its functional capacity to yield bioactive metabolites from dietary sources. Therefore, this study assessed gut microbiome composition and its related functional capacity to metabolize fruit (poly)phenols in individuals with prediabetes and insulin resistance (PreDM-IR, n = 26) compared to a metabolically healthy Reference group (n = 10). Methods: Shotgun sequencing was used to characterize gut microbiome composition. Targeted quantitative metabolomic analyses of plasma and urine collected over 24 h were used to assess microbial-derived metabolites in response to a (poly)phenol-rich raspberry test drink. Results: PreDM-IR compared to the Reference group: (1) enriched Blautia obeum and Blautia wexlerae and depleted Bacteroides dorei and Coprococcus eutactus. Akkermansia muciniphila and Bacteroides spp. were depleted in the lean PreDM-IR subset; and (2) impaired microbial catabolism of select (poly)phenols resulting in lower 3,8-dihydroxy-urolithin (urolithin A), phenyl-γ-valerolactones and various phenolic acids concentrations (p < 0.05). Controlling for obesity revealed relationships with microbial species that may serve as metagenomic markers of diabetes development and therapeutic targets. Conclusions: Data provide insight from multi-omics approaches to advance knowledge at the diet–gut–disease nexus serving as a platform for devising dietary strategies to improve metabolic health. Full article