Flavonifractor Plautii Research Articles

Gut microbiota dysbiosis in Chinese children with type 1 diabetes mellitus: An observational study.

BACKGROUNDGut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus (T1DM). However, the alterations in the gut microbiota and their correlation with fasting blood glucose (FBG) in Chinese children with T1DM remain unclear. AIMTo investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.METHODSSamples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained, to explore the structural and functional alterations in the fecal microbiota. The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument, and the association with FBG were analyzed. RESULTSWe found that the bacterial diversity was significantly increased in the T1DM-associated fecal microbiota, and changes in the microbial composition were observed at different taxonomic levels. The T1DM-reduced differential taxa, such as Bacteroides vulgatus ATCC8482, Bacteroides ovatus, Bacteroides xylanisolvens, and Flavonifractor plautii, were negatively correlated with FBG, while the T1DM-enriched taxa, such as Blautia, Eubacterium hallii group, Anaerostipes hadrus, and Dorea longicatena, were positively correlated with FBG. Bacteroides vulgatus ATCC8482, Bacteroides ovatus, the Eubacterium hallii group, and Anaerostipes hadrus, either alone or in combination, could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls. In addition, the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities, such as glycan biosynthesis and metabolism and lipid metabolism, which might play vital roles in the pathogenesis and development of T1DM. CONCLUSIONOur present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.

Ecological and network analyses identify four microbial species with potential significance for the diagnosis/treatment of ulcerative colitis (UC)

BackgroundUlcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis.ResultsIn total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic “pathogens” (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic “pathogens” associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect.ConclusionsOur results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.

Oral Administration of Flavonifractor plautii, a Bacteria Increased With Green Tea Consumption, Promotes Recovery From Acute Colitis in Mice via Suppression of IL-17.

Flavonifractor plautii (FP) has been reported to participate in the metabolism of catechins in the human gut. However, there is limited information on the immune regulatory effects of this bacterium. We confirmed that the administration of green tea increases the abundance of FP in the gut microbiota and investigated the effect of FP in a mouse colitis model. Mice were orally administered FP for 10 consecutive days; colonic inflammation was evaluated daily on the basis of stool consistency, gross rectal bleeding, and body weight. In the dextran sodium sulfate model, FP-exposed animals exhibited lower levels of inflammation and strong inhibition of interleukin (IL)-17 signaling. Moreover, lipoteichoic acid from FP was identified as the active component mediating IL-17 suppression. Thus, oral administration of FP appears to modulate gut inflammation and represents a viable and inexpensive oral microbial therapeutic.

Discovery of an ene-reductase for initiating flavone and flavonol catabolism in gut bacteria

Gut microbial transformations of flavonoids, an enormous class of polyphenolic compounds abundant in plant-based diets, are closely associated with human health. However, the enzymes that initiate the gut microbial metabolism of flavones and flavonols, the two most abundant groups of flavonoids, as well as their underlying molecular mechanisms of action remain unclear. Here, we discovered a flavone reductase (FLR) from the gut bacterium, Flavonifractor plautii ATCC 49531 (originally assigned as Clostridium orbiscindens DSM 6740), which specifically catalyses the hydrogenation of the C2–C3 double bond of flavones/flavonols and initiates their metabolism as a key step. Crystal structure analysis revealed the molecular basis for the distinct catalytic property of FLR. Notably, FLR and its widespread homologues represent a class of ene-reductases that has not been previously identified. Genetic and biochemical analyses further indicated the importance of FLR in gut microbial consumption of dietary and medicinal flavonoids, providing broader insight into gut microbial xenobiotic transformations and possible guidance for personalized nutrition and medicine.

Gut-derived Flavonifractor species variants are differentially enriched during in vitro incubation with quercetin

Flavonoids are a common component of the human diet with widely reported health-promoting properties. The gut microbiota transforms these compounds affecting the overall metabolic outcome of flavonoid consumption. Flavonoid-degrading bacteria are often studied in pure and mixed cultures but the multiple interactions between quercetin-degraders and the rest of the community have been overlooked. In this study, a comparative metataxonomic analysis of fecal communities supplemented with the flavonoid quercetin led us to identify a potential competitive exclusion interaction between two sequence variants related to the flavonoid-degrading species, Flavonifractor plautii, that belong to the same genus but different species. During incubation of fecal slurries with quercetin, the relative abundance of these two variants was inversely correlated; one variant, ASV_65f4, increased in relative abundance in half of the libraries and the other variant, ASV_a45d, in the other half. This pattern was also observed with 6 additional fecal samples that were transplanted into germ-free mice fed two different diets. Mouse’s diet did not change the pattern of dominance of either variant, and initial relative abundances did not predict which one ended up dominating. Potential distinct metabolic capabilities of these two Flavonifractor-related species were evidenced, as only one variant, ASV_65f4, became consistently enriched in complex communities supplemented with acetate but without quercetin. Genomic comparison analysis of the close relatives of each variant revealed that ASV_65f4 may be an efficient utilizer of ethanolamine which is formed from the phospholipid phosphatidylethanolamine that is abundant in the gut and feces. Other discordant features between ASV_65f4- and ASV_a45d-related groups may be the presence of flagellar and galactose-utilization genes, respectively. Overall, we showed that the Flavonifractor genus harbors variants that present a pattern of negative co-occurrence and that may have different metabolic and morphological traits, whether these differences affect the dynamic of quercetin degradation warrants further investigation.

The associations of the gut microbiome composition and short-chain fatty acid concentrations with body fat distribution in children

Previous studies linking the gut microbiome with childhood obesity largely used the body mass index to measure obesity and reached inconsistent findings. Little evidence has linked the gut microbiome to regional body fat deposition. We investigated whether the abundance of specific taxa in the gut microbiota and the concentrations of short-chain fatty acids (SCFAs) were associated with the content and regional deposition of body fat in children. This cross-sectional study involved 236 children aged 6-9 years. The fat mass contents/percentages in the total body and the android, gynoid, and limb regions were determined by dual-energy X-ray absorptiometry, and the android-to-gynoid fat mass ratio and fat-to-lean mass ratios were calculated. Fecal samples were subjected to16S rRNA amplicon sequencing, and the fecal SCFA concentrations were quantified via high-performance liquid chromatography. A weighted gene co-expression network analysis identified seven modules of co-expressed operational taxonomic units (OTUs). A total of 57 OTUs from 4 key modules were selected for further analysis. After adjustment of covariates and controlling for the false discovery rate (FDR), a multiple linear regression analysis revealed significant correlations of the abundances of some OTUs with obesity and body fat measures. For instance, the OTUs classified to the species Ruminococcus gnavus and Flavonifractor plautii showed significant negative correlations with the total and regional body fat (β:-0.250 to-0.180, PFDR: 0.041-0.049), whereas OTUs belonging to the genera Blautia and Romboutsia exhibited positive correlations with body fat measures (β: 0.184-0.222, PFDR: 0.041-0.049). The fecal concentrations of acetic, propionic, and butyric acids and total SCFAs were significantly positively correlated with various parameters of body fat distribution (β: 0.160-0.275, PFDR: <0.001-0.042). The gut microbiome and SCFAs are significantly associated with obesity and body fat distribution in pediatric population.

Oral administration of Flavonifractor plautii attenuates inflammatory responses in obese adipose tissue.

Adipose tissue inflammation enhances the symptoms of metabolic syndrome. Flavonifractor plautii, a bacterium present in human feces, has been reported to participate in the metabolism of catechin in the gut. The precise function of F. plautii remains unclear. We assessed the immunoregulatory function of F. plautii both in vitro and in vivo. In vitro, we showed that both viable and heat-killed F. plautii attenuated TNF-α transcript accumulation in lipopolysaccharide-stimulated RAW 264.7 cells. For the in vivo experiment, male C57BL/6 were placed on a high-fat diet (HFD) for 11weeks. During the final two weeks on the HFD, the animals were administered with F. plautii by once-daily oral gavage. The oral administration of F. plautii attenuated the increase in TNF-α transcription otherwise seen in the epididymal adipose tissue of HFD-fed obese mice (HFD + F. plautii). The composition of the microbial population (at the genus level) in the cecal contents of the HFD + F. plautii mice was altered considerably. In particular, the level of Sphingobium was decreased significantly, and that of Lachnospiraceae was increased significantly, in the HFD + F. plautii group. Obesity is closely associated with the development of inflammation in adipose tissue. F. plautii may be involved in inhibition of TNF-α expression in inflammatory environments. Our results demonstrated that F. plautii may be useful for alleviating the inflammatory responses of adipose tissue.

Complete Genome Sequence of Flavonifractor plautii JCM 32125T.

We report the complete genome sequence of Flavonifractor plautii JCM 32125T (=VPI 0310T). The genome consists of a single circular chromosome of 3,985,392 bp (G+C content, 60.9%) and was predicted to contain 3 complete sets of rRNA genes, 63 tRNA genes, and 3,764 protein-coding sequences.

Oral Administration of Flavonifractor plautii Strongly Suppresses Th2 Immune Responses in Mice.

The bacterium Flavonifractor plautii (FP), which is found in human feces, has been reported to participate in catechin metabolism in the gut, but this bacterium's effects on immune function are unclear. We assessed the effect of oral administration of FP on the immune response in ovalbumin (OVA) -sensitized mice. We demonstrated that the FP treatment suppressed interleukin (IL)-4 in splenocytes and OVA-specific IgE production in serum from OVA-sensitized mice. Moreover, oral administration of FP augmented CD4+CD25+ T cells and CD103+CD11c+ DCs. In animals of the FP group, the proportion of FP was increased in the mesenteric lymph nodes (MLNs), as was the proportion of Deferribacteres in the cecum. Oral administration of FP may inhibit the Th2 immune response by incorporation into the MLNs and/or by inducing changes in the gut microbiota. Thus, FP may be useful in alleviating antigen-induced Th2 immune responses.

Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment.

Introduction. Ankylosing spondylitis (AS) is a systemic progressive disease with an unknown etiology that may be related to the gut microbiome. Therefore, a more thorough understanding of its pathogenesis is necessary for directing future therapy.Aim. We aimed to determine the differences in intestinal microbial composition between healthy individuals and patients with AS who received and who did not receive treatment interventions. In parallel, the pathology of AS in each patient was analysed to better understand the link between AS treatment and the intestinal microbiota of the patients.Methodology. Sixty-six faecal DNA samples, including 37 from healthy controls (HCs), 11 from patients with untreated AS (NM), 7 from patients treated with nonsteroidal anti-inflammatory drugs (e.g. celecoxib; WM) and 11 from patients treated with Chinese herbal medicine (CHM), such as the Bushen–Qiangdu–Zhilv decoction, were collected and used in the drug effect analysis. All samples were sequenced using Illumina HiSeq 4000 and the microbial composition was determined.Results. Four species were enriched in the patients with AS: Flavonifractor plautii , Oscillibacter , Parabacteroides distasonis and Bacteroides nordii (HC vs. NM, P<0.05); only F. plautii was found to be significantly changed in the NM-HC comparison. No additional species were found in the HC vs. CHM analysis, which indicated a beneficial effect of CHM in removing the other three strains. F. plautii was found to be significantly increased in the comparison between the HC and WM groups, along with four other species ( Clostridium bolteae , Clostridiales bacterium 1_7_47FAA, C. asparagiforme and C. hathewayi ). The patients with AS harboured more bacterial species associated with carbohydrate metabolism and glycan biosynthesis in their faeces. They also had bacterial profiles less able to biodegrade xenobiotics or synthesize and transport vitamins.Conclusion. The gut microbiota of the patients with AS varied from that of the HCs, and the treatment had an impact on this divergence. Our data provide insight that could guide improvements in AS treatment.

Association of Flavonifractor plautii, a Flavonoid-Degrading Bacterium, with the Gut Microbiome of Colorectal Cancer Patients in India.

Recently, dysbiosis in the human gut microbiome and shifts in the relative abundances of several bacterial species have been recognized as important factors in colorectal cancer (CRC). However, these studies have been carried out mainly in developed countries where CRC has a high incidence, and it is unclear whether the host-microbiome relationships deduced from these studies can be generalized to the global population. To test if the documented associations between the microbiome and CRC are conserved in a distinct context, we performed metagenomic and metabolomic association studies on fecal samples from 30 CRC patients and 30 healthy controls from two different locations in India, followed by a comparison of CRC data available from other populations. We confirmed the association of Bacteroides and other bacterial taxa with CRC that have been previously reported in other studies. However, the association of CRC with Flavonifractor plautii in Indian patients emerged as a novel finding. The plausible role of F. plautii appears to be linked with the degradation of beneficial anticarcinogenic flavonoids, which was also found to be significantly correlated with the enzymes and modules involved in flavonoid degradation within Indian CRC samples. Thus, we hypothesize that the degradation of beneficial flavonoids might be playing a role in cancer progression within this Indian cohort. We also identified 20 potential microbial taxonomic markers and 33 potential microbial gene markers that discriminate the Indian CRC from healthy microbiomes with high accuracy based on machine learning approaches.IMPORTANCE This study provides novel insights on the CRC-associated microbiome of a unique cohort in India, reveals the potential role of a new bacterium in CRC, and identifies cohort-specific biomarkers, which can potentially be used in noninvasive diagnosis of CRC. The study gains additional significance, as India is among the countries with a very low incidence of CRC, and the diet and lifestyle in India have been associated with a distinct gut microbiome in healthy Indians compared to other global populations. Thus, in this study, we hypothesize a unique relationship between CRC and the gut microbiome in an Indian population.

An enzymatic pathway in the human gut microbiome that converts A to universal O type blood.

Access to efficient enzymes that can convert A and B type red blood cells to 'universal' donor O would greatly increase the supply of blood for transfusions. Here we report the functional metagenomic screening of the human gut microbiome for enzymes that can remove the cognate A and B type sugar antigens. Among the genes encoded in our library of 19,500 expressed fosmids bearing gut bacterial DNA, we identify an enzyme pair from the obligate anaerobe Flavonifractor plautii that work in concert to efficiently convert the A antigen to the H antigen of O type blood, via a galactosamine intermediate. The X-ray structure of the N-acetylgalactosamine deacetylase reveals the active site and mechanism of the founding member of an esterase family. The galactosaminidase expands activities within the CAZy family GH36. Their ability to completely convert A to O of the same rhesus type at very low enzyme concentrations in whole blood will simplify their incorporation into blood transfusion practice, broadening blood supply.

Gut microbial beta-glucuronidase and glycerol/diol dehydratase activity contribute to dietary heterocyclic amine biotransformation

BackgroundConsuming red and processed meat has been associated with an increased risk of colorectal cancer (CRC), which is partly attributed to exposure to carcinogens such as heterocyclic amines (HCA) formed during cooking and preservation processes. The interaction of gut microbes and HCA can result in altered bioactivities and it has been shown previously that human gut microbiota can transform mutagenic HCA to a glycerol conjugate with reduced mutagenic potential. However, the major form of HCA in the colon are glucuronides (HCA-G) and it is not known whether these metabolites, via stepwise microbial hydrolysis and acrolein conjugation, are viable precursors for glycerol conjugated metabolites. We hypothesized that such a process could be concurrently catalyzed by bacterial beta-glucuronidase (B-GUS) and glycerol/diol dehydratase (GDH) activity. We therefore investigated how the HCA-G PhIP-N2-β-D-glucuronide (PhIP-G), a representative liver metabolite of PhIP (2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), which is the most abundant carcinogenic HCA in well-cooked meat, is transformed by enzymatic activity of human gut microbial representatives of the phyla Firmicutes, Bacteroidetes, and Proteobacteria.ResultsWe employed a combination of growth and enzymatic assays, and a bioanalysis approach combined with metagenomics. B-GUS of Faecalibacterium prausnitzii converted PhIP-G to PhIP and GDH of Flavonifractor plautii, Blautia obeum, Eubacterium hallii, and Lactobacillus reuteri converted PhIP to PhIP-M1 in the presence of glycerol. In addition, B-GUS- and GDH-positive bacteria cooperatively converted PhIP-G to PhIP-M1. A screen of genes encoding B-GUS and GDH was performed for fecal microbiome data from healthy individuals (n = 103) and from CRC patients (n = 53), which revealed a decrease in abundance of taxa with confirmed GDH and HCA transformation activity in CRC patients.ConclusionsThis study for the first time demonstrates that gut microbes mediate the stepwise transformation of PhIP-G to PhIP-M1 via the intermediate production of PhIP. Findings from this study suggest that targeted manipulation with gut microbes bearing specific functions, or dietary glycerol supplementation might modify gut microbial activity to reduce HCA-induced CRC risk.

Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome

Accurate diagnosis and stratification of children with irritable bowel syndrome (IBS) remain challenging. Given the central role of recurrent abdominal pain in IBS, we evaluated the relationships of pediatric IBS and abdominal pain with intestinal microbes and fecal metabolites using a comprehensive clinical characterization and multiomics strategy. Using rigorous clinical phenotyping, we identified preadolescent children (aged 7 to 12 years) with Rome III IBS (n = 23) and healthy controls (n = 22) and characterized their fecal microbial communities using whole-genome shotgun metagenomics and global unbiased fecal metabolomic profiling. Correlation-based approaches and machine learning algorithms identified associations between microbes, metabolites, and abdominal pain. IBS cases differed from controls with respect to key bacterial taxa (eg, Flavonifractor plautii and Lachnospiraceae bacterium 7_1_58FAA), metagenomic functions (eg, carbohydrate metabolism and amino acid metabolism), and higher-order metabolites (eg, secondary bile acids, sterols, and steroid-like compounds). Significant associations between abdominal pain frequency and severity and intestinal microbial features were identified. A random forest classifier built on metagenomic and metabolic markers successfully distinguished IBS cases from controls (area under the curve, 0.93). Leveraging multiple lines of evidence, intestinal microbes, genes/pathways, and metabolites were associated with IBS, and these features were capable of distinguishing children with IBS from healthy children. These multi-omics features, and their links to childhood IBS coupled with nutritional interventions, may lead to new microbiome-guided diagnostic and therapeutic strategies.

Using Decision Tree Aggregation with Random Forest Model to Identify Gut Microbes Associated with Colorectal Cancer.

The imbalance of human gut microbiota has been associated with colorectal cancer. In recent years, metagenomics research has provided a large amount of scientific data enabling us to study the dedicated roles of gut microbes in the onset and progression of cancer. We removed unrelated and redundant features during feature selection by mutual information. We then trained a random forest classifier on a large metagenomics dataset of colorectal cancer patients and healthy people assembled from published reports and extracted and analysed the information from the learned decision trees. We identified key microbial species associated with colorectal cancers. These microbes included Porphyromonas asaccharolytica, Peptostreptococcus stomatis, Fusobacterium, Parvimonas sp., Streptococcus vestibularis and Flavonifractor plautii. We obtained the optimal splitting abundance thresholds for these species to distinguish between healthy and colorectal cancer samples. This extracted consensus decision tree may be applied to the diagnosis of colorectal cancers.

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

BackgroundInflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis.ResultsIgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not.ConclusionUsing IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.

Lawsonibacter asaccharolyticus gen. nov., sp. nov., a butyrate-producing bacterium isolated from human faeces.

An obligately anaerobic, Gram-positive, non-spore-forming, straight rod-shaped bacterium, designated strain 3BBH22T, was isolated from a faecal sample of a healthy Japanese woman. The 16S rRNA gene sequence analysis showed that strain 3BBH22T formed a monophyletic cluster with species in the genera Pseudoflavonifractor and Flavonifractor within the family Ruminococcaceae and had highest similarity to Pseudoflavonifractor capillosus ATCC 29799T (96.7 % sequence similarity), followed by Flavonifractor plautii ATCC 29863T (96.4 %). Acetate and butyrate were produced by strain 3BBH22T as metabolic end-products. The major cellular fatty acids were C14 : 0, C16 : 0, C18 : 1ω9c, C16 : 0 dimethyl acetal, C18 : 0 and C18 : 2ω6,9c. No respiratory quinones were detected. In contrast to F. plautii JCM 32125T, strain 3BBH22T did not degrade quercetin, one of the flavonoids. P. capillosus JCM 32126T also did not. Strain 3BBH22T was differentiated from P. capillosus JCM 32126T by its inability to hydrolyse aesculin. The G+C content of the genomic DNA was 61.2±1.0 mol%. On the basis of these data and the phylogenetic tree based on 89 proteins, strain 3BBH22T represents a novel species in a novel genus of the family Ruminococcaceae, for which the name Lawsonibacter asaccharolyticus gen. nov., sp. nov. is proposed. The type strain of L. asaccharolyticus is 3BBH22T (=JCM 32166T=DSM 106493T).

The urinary phenolic acid profile varies between younger and older adults after a polyphenol-rich meal despite limited differences in in vitro colonic catabolism

PurposeTo investigate whether age influences colonic polyphenol metabolism.MethodsHealthy participants, younger (n = 8; 23–43 years) and older (n = 13; 51–76 years), followed a 3-day low-polyphenol diet (LPD) and a 3-day high-polyphenol diet (HPD). Urinary phenolic acids (PA), short chain fatty acids (SCFA), pH and gas were monitored, alongside selected colonic bacteria. Human faecal in vitro fermentations of rutin with or without raftiline were used to evaluate the gut microbiota capacity in a subset of both groups.ResultsTotal urinary PA were higher in the older group after HPD compared to the younger group (1.5-fold; p = 0.04), with no difference between groups in terms of a change between diets (Δ high-low diet). While 17 PA were detected in all younger participants after HPD, a narrower range (n = 8 to 16 PA) was detected in most (n = 9/13) older participants, with lower level of benzoic acid (19-fold; p = 0.03), vanillic acid (4.5-fold; p = 0.04) but higher hippuric acid (2.7-fold; p = 0.03). Faecal SCFA concentration did not change after HPD within group, with similar differential excretion (Δ high-low diet) between groups. There were no differences between groups for faecal pH, total, faecal bacteria including Flavonifractor plautii, bifidobacteria, and bacteroides. In human in vitro faecal fermentations, seven PAs were detected in both groups after 24 h of rutin fermentation, with no quantitative and modest qualitative differences between groups. Total SCFA in faecal fermentation did not differ between groups, except for butyric acid (twofold higher in the older group; p = 0.009) when rutin was fermented with raftiline over 24 h.ConclusionsUrinary phenolic acids were less diverse in older participants despite limited difference in functional capacity of in vitro faecal fermentations.

Body Mass Index and Sex Affect Diverse Microbial Niches within the Gut.

Gut microbiota is considered a separate organ with endocrine capabilities, actively contributing to tissue homeostasis. It consists of at least two separate microbial populations, the lumen-associated (LAM) and the mucosa-associated microbiota (MAM). In the present study, we compared LAM and MAM, by collecting stools and sigmoid brush samples of forty adults without large-bowel symptoms, and through a 16S rRNA gene next-generation sequencing (NGS) approach. MAM sample analysis revealed enrichment in aerotolerant Proteobacteria, probably selected by a gradient of oxygen that decreases from tissue to lumen, and in Streptococcus and Clostridium spp., highly fermenting bacteria. On the other hand, LAM microbiota showed an increased abundance in Bacteroides, Prevotella, and Oscillospira, genera able to digest and to degrade biopolymers in the large intestine. Predicted metagenomic analysis showed LAM to be enriched in genes encoding enzymes mostly involved in energy extraction from carbohydrates and lipids, whereas MAM in amino acid and vitamin metabolism. Moreover, LAM and MAM communities seemed to be influenced by different host factors, such as diet and sex. LAM is affected by body mass index (BMI) status. Indeed, BMI negatively correlates with Faecalibacterium prausnitzii and Flavonifractor plautii abundance, putative biomarkers of healthy status. In contrast, MAM microbial population showed a significant grouping according to sex. Female MAM was enriched in Actinobacteria (with an increased trend of the genus Bifidobacterium), and a significant depletion in Veillonellaceae. Interestingly, we found the species Gemmiger formicilis to be associated with male and Bifidobacterium adolescentis, with female MAM samples. In conclusion, our results suggest that gut harbors microbial niches that differ in both composition and host factor susceptibility, and their richness and diversity may be overlooked evaluating only fecal samples.

Flavonifractor (Eubacterium) plautii bloodstream infection following acute cholecystitis.

Flavonifractor plautii (formerly Eubacterium plautii) is an anaerobic gram positive rod shaped bacterium belonging to the family of Clostridiales, and a common member of the human gut microbiome. However, it is very rarely isolated from clinical human specimens, so data about its clinical significance are scarce. Here we report of a bloodstream infection due to F. plautii following gangrenous cholecystitis in a 69 year old man. After cholecystectomy and empirical antimicrobial treatment with ceftriaxone and metronidazole the patient recovered.F. plautii was the only bacterium detected in blood culture, suggesting that it might have been causative for cholecystitis. Antimicrobial resistance testing identified decreased susceptibilities against linezolid and penicillin indicating that a targeted therapy might be necessary. F. plautii can be considered a potential pathogen for cholecystitis.