Bifidobacteriaceae Family Research Articles

Gut Microbiota Composition Is Causally Linked to Multiple Sclerosis: A Mendelian Randomization Analysis.

Accumulating evidence links the microbial communities inhabiting the gut to the pathophysiological processes underlying multiple sclerosis (MS). However, most studies on the microbiome in MS are correlative in nature, thus being at risk of confounding and reverse causality. Mendelian randomization (MR) analyses allow the estimation of the causal relationship between a risk factor and an outcome of interest using genetic variants as proxies for environmental exposures. Here, we performed a two-sample MR to assess the causality between the gut microbiome and MS. We extracted genetic instruments from summary statistics from three large genome-wide association studies (GWASs) on the gut microbiome (18,340, 8959, and 7738 subjects). The exposure data were derived from the latest GWAS on MS susceptibility (47,429 patients and 68,374 controls). We pinpointed several microbial strains whose abundance is linked with enhanced MS risk (Actinobacteria class, Bifidobacteriaceae family, Lactobacillus genus) or protection (Prevotella spp., Lachnospiranaceae genus, Negativibacillus genus). The largest risk effect was seen for Ruminococcus Torques (OR, 2.89, 95% C.I. 1.67-5, p = 1.51 × 10-4), while Akkermansia municiphila emerged as strongly protective (OR, 0.43, 95% C.I. 0.32-0.57, p = 1.37 × 10-8). Our findings support a causal relationship between the gut microbiome and MS susceptibility, reinforcing the relevance of the microbiome-gut-brain axis in disease etiology, opening wider perspectives on host-environmental interactions for MS prevention.

Dissecting the association between gut microbiota, body mass index and specific depressive symptoms: a mediation Mendelian randomisation study

BackgroundObservational studies highlight the association between gut microbiota (GM) composition and depression; however, evidence for the causal relationship between GM and specific depressive symptoms remains lacking.AimsWe aimed to evaluate the...

HMOs Impact the Gut Microbiome of Children and Adults Starting from Low Predicted Daily Doses.

Recent studies suggest that the dietary intake of human milk oligosaccharides (HMOs) provides health benefits from infancy up to adulthood. Thus far, beneficial changes in the adult gut microbiome have been observed at oral doses of 5-20 g/day of HMOs. Efficacy of lower doses has rarely been tested. We assessed four HMO molecular species-2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), and 6'Sialyllactose (6'SL)-at predicted doses from 0.3 to 5 g/day for 6-year-old children and adults (n = 6 each), using ex vivo SIFR® technology (Cryptobiotix, Ghent, Belgium). This technology employing bioreactor fermentation on fecal samples enables us to investigate microbial fermentation products that are intractable in vivo given their rapid absorption/consumption in the human gut. We found that HMOs significantly increased short-chain fatty acids (SCFAs), acetate, propionate (in children/adults), and butyrate (in adults) from predicted doses of 0.3-0.5 g/day onwards, with stronger effects as dosing increased. The fermentation of 6'SL had the greatest effect on propionate, LNnT most strongly increased butyrate, and 2'FL and 3'SL most strongly increased acetate. An untargeted metabolomic analysis revealed that HMOs enhanced immune-related metabolites beyond SCFAs, such as aromatic lactic acids (indole-3-lactic acid/3-phenyllactic acid) and 2-hydroxyisocaproic acid, as well as gut-brain-axis-related metabolites (γ-aminobutyric acid/3-hydroxybutyric acid/acetylcholine) and vitamins. The effects of low doses of HMOs potentially originate from the highly specific stimulation of keystone species belonging to, for example, the Bifidobacteriaceae family, which had already significantly increased at doses of only 0.5 g/day LNnT (adults) and 1 g/day 2'FL (children/adults).

Macauba (Acrocomia aculeata) pulp oil has the potential to enhance the intestinal barrier morphology, goblet cell proliferation and gut microbiota composition in mice fed a high-fat diet.

Macauba (Acrocomia aculeata) is a palm tree native from Brazil, whose pulp is rich in oil that has a high content of oleic acid and carotenoids. Macauba pulp oil can bring health benefits due to its bioactive compounds; however, its effects on gut health are unknown. Thus, the objective of this study was to evaluate the effect of macauba pulp oil on the intestinal health in mice fed a high-fat (HF) diet. Male C57BL1/6 mice were randomly divided into three groups (10 animals/group): control diet, HF diet and HF diet with 4 % of macauba pulp oil (HFM). Concentration of short-chain fatty acids (SCFA), faecal pH and histomorphometric analysis of the colon were performed. Content of colon samples was used on microbiome analysis using 16S rRNA amplicon sequencing. Animals from the HFM group had higher butyric acid content and goblet cells number, greater circular and longitudinal muscle layer and higher α-diversity compared with the HF group. Moreover, consumption of MPO reduced Desulfobacterota phylum, Ruminococcaceae, Oscillospiraceae, Prevotellaceae, Bifidobacteriaceae family, Faecalibacterium, Prevotella, Ruminococcus and Enterorhabdus genus. Therefore, macauba pulp oil was able to modulate the gut microbiota and enhance intestinal barrier morphology, showing preventive effects on gut dysbiosis in mice fed a HF diet.

Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study.

We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Microbial and immune faecal determinants in infants hospitalized with COVID-19 reflect bifidobacterial dysbiosis and immature intestinal immunity

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, seriously endangering human health. Although SARS‐CoV‐2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal (GI) symptoms at a higher rate than adults. The aim of this work was to evaluate faeces as a source of potential biomarkers of severity in the paediatric population, with an emphasis on intestinal microbiota and faecal immune mediators, trying to identify possible dysbiosis and immune intestinal dysfunction associated with the risk of hospitalization. This study involved 19 patients with COVID-19 under 24 months of age hospitalized during the pandemic at 6 different hospitals in Spain, and it included a comparable age-matched healthy control group (n = 18). Patients and controls were stratified according to their age in two groups: newborns or young infants (from 0 to 3 months old) and toddlers (infants from 6 to 24 months old). To characterize microbial intestinal communities, sequencing with Illumina technology of total 16S rDNA amplicons and internal transcribed spacer (ITS) amplicons of bifidobacteria were used. Faecal calprotectin (FC) and a range of human cytokines, chemokines, and growth factors were measured in faecal samples using ELISA and a multiplex system. Significant reduction in the abundance of sequences belonging to the phylum Actinobacteria was found in those infants with COVID-19, as well as in the Bifidobacteriaceae family. A different pattern of bifidobacteria was observed in patients, mainly represented by lower percentages of Bifidobacterium breve, as compared with controls. In the group of hospitalized young infants, FC was almost absent compared to age-matched healthy controls. A lower prevalence in faecal excretion of immune factors in these infected patients was also observed.Conclusion: Hospitalized infants with COVID-19 were depleted in some gut bacteria, such as bifidobacteria, in particular Bifidobacterium breve, which is crucial for the proper establishment of a functional intestinal microbiota, and important for the development of a competent immune system. Our results point to a possible immature immune system at intestine level in young infants infected by SARS-CoV2 requiring hospitalization.What is Known:• Although SARS‐CoV‐2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal symptoms at a higher rate than adults.• Changes in microbial composition have been described in COVID-19 adult patients, although studies in children are limited.What is New:• The first evidence that hospitalized infants with COVID-19 during the pandemic had a depletion in bifidobacteria, particularly in Bifidobacterium breve, beneficial gut bacteria in infancy that are crucial for the proper establishment of a competent immune system.• In young infants (under 3 months of age) hospitalized with SARS-CoV2 infection, the aberrant bifidobacterial profile appears to overlap with a poor intestinal immune development as seen by calprotectin and the trend of immunological factors excreted in faeces.

Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization.

Our aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods. We extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism. Two taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus. Gut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases.

Effects of bowel cleansing on the composition of the gut microbiota in inflammatory bowel disease patients and healthy controls.

In patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC), numerous cases of exacerbations could be observed after colonoscopy, raising the possible pathogenetic effect of colonic microbiota alterations in IBD flare. We aimed to investigate the changes in the fecal microbiota composition in IBD patients influenced by the bowel preparation with sodium picosulfate. We enrolled patients with IBD undergoing bowel preparation for colonoscopy in the prospective cohort study. The control group (Con) comprised non-IBD patients who underwent colonoscopy. Clinical data, blood, and stool samples were collected before colonoscopy (timepoint A), 3 days later (timepoint B), and 4 weeks later (timepoint C). Disease activity and gut microbiota changes were assessed at each timepoint. Fecal microbiota structure - at family level - was determined by sequencing the V4 region of the 16S rRNA gene. Statistical analysis included differential abundance analysis and Mann-Whitney tests. Forty-one patients (9 CD, 13 UC, and 19 Con) were included. After bowel preparation, alpha diversity was lower in the CD group than in the UC (p = 0.01) and Con (p = 0.02) groups at timepoint B. Alpha diversity was significantly higher in the UC group than in the CD and Con (p = 0.03) groups at timepoint C. Beta diversity difference differed between the IBD and Con (p = 0.001) groups. Based on the differential abundance analysis, the Clostridiales family was increased, whereas the Bifidobacteriaceae family was decreased in CD patients compared to the Con at timepoint B. Bowel preparation may change the fecal microbial composition in IBD patients, which may have a potential role in disease exacerbation after bowel cleansing.

Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogen Candida albicans.

The human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via a process called colonization resistance. Here, we investigated the antagonistic activity of human gut bacteria towards Candida albicans, an opportunistic fungal pathogen that can cause severe infections in susceptible individuals. Coculture batch incubations of C. albicans in the presence of faecal microbiota from six healthy individuals revealed varying levels of inhibitory activity against C. albicans. 16S rRNA gene amplicon profiling of these faecal coculture bacterial communities showed that the Bifidobacteriaceae family, and Bifidobacterium adolescentis in particular, were most correlated with antagonistic activity against C. albicans. Follow-up mechanistic studies performed under anaerobic conditions confirmed that culture supernatants of Bifidobacterium species, particularly B. adolescentis, inhibited C. albicans in vitro. Fermentation acids (FA), including acetate and lactate, present in the bifidobacterial supernatants were important contributors to inhibitory activity. However, increasing the pH of both bacterial supernatants and mixtures of FA reduced their anti-Candida effects, indicating a combinatorial effect of prevailing pH and FA. This work, therefore, demonstrates potential mechanisms underpinning gut microbiome-mediated colonization resistance against C. albicans, and identifies particularly inhibitory components such as bifidobacteria and FA as targets for further study.

Gut microbiota and physical exercise in obesity and diabetes – A systematic review

Background and aimThe gut microbiota (GM) plays an essential role in maintaining health, and imbalance in its composition is associated with the physiopathogenesis of metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). Diet and antibiotics are known modulators of GM, but the influence of physical exercise in modulating the diversity and abundance of hindgut bacteria is still poorly understood. The aim of this systematic review was to investigate the scientific evidence about the effect of physical exercise on GM modulation in subjects with obesity and T2DM. Methods and resultsA search in PubMed, Web of Science, Scopus, Cochrane and Embase databases using keywords related to gut microbiota, physical exercise and metabolic diseases was performed. Eight clinical studies met the inclusion criteria, six in subjects with obesity and two in individuals with T2DM. In three studies carried out in individuals with obesity, exercise was able to positively modulate the diversity of GM and the abundance of some species of bacteria, mostly by increasing the Bifidobacteriaceae family, and the Bacteroides and Akkermansia genera, and by decreasing the Proteobacteria phylum. The studies in subjects with T2DM found that physical exercise may reduce metabolic endotoxemia markers. ConclusionsPhysical exercise may be a beneficial modulation strategy of GM composition in metabolic diseases, specifically aerobic exercises carried out for at least 6 weeks with moderate or high intensity. Nevertheless, well-designed clinical trials are needed to clarify the role of physical exercise on GM in subjects with obesity and T2DM.

Dysbiosis of Gut Microbiota Promotes Hepatocellular Carcinoma Progression by Regulating the Immune Response.

Method This study included 74 Chinese male patients with HCC. They were divided into early (n = 19), intermediate (n = 37), and terminal (n = 18) groups, referred to as Barcelona Clinic Liver Cancer stage 0+A, B, and C+D, respectively. Paired fecal and plasma samples were collected. Microbial composition and profiles were analyzed by 16S rRNA gene sequencing. The levels of gut damage marker (regenerating islet-derived protein 3α (REG3α)) and microbial translocation markers (soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), peptidoglycan recognition proteins (PGRPs)) were determined in plasma samples of patients by ELISA. Twenty plasma cytokine and chemokines were determined by Luminex. Results In early, intermediate, and terminal groups, the abundance of the Bifidobacteriaceae family decreased significantly (3.52%, 1.55%, and 0.56%, respectively, P = 0.003), while the abundance of the Enterococcaceae family increased significantly (1.6%, 2.9%, and 13.4%, respectively, P = 0.022). Levels of REG3α and sCD14 were markedly elevated only in the terminal group compared with the early (P = 0.025 and P = 0.048) and intermediate groups (P = 0.023 and P = 0.046). The level of LBP significantly increased in the intermediate (P = 0.035) and terminal (P = 0.025) groups compared with the early group. The PGRP levels were elevated only in the terminal group compared with the early group (P = 0.018). The ratio of Enterococcaceae to Bifidobacteriaceae was significantly associated with the levels of REG3α, LBP, sCD14, and PGRPs. With HCC progression, increased levels of inflammatory cytokines accompanied by a T cell-immunosuppressive response and microbial translocation were observed. Conclusion Gut microbiota compositional and functional shift, together with elevated gut damage and microbial translocation, may promote HCC development by stimulating inflammatory response and suppressing T cell response.

Consistent Prebiotic Effects of Carrot RG-I on the Gut Microbiota of Four Human Adult Donors in the SHIME® Model despite Baseline Individual Variability.

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.

Bifidobacteriaceae Family Diversity in Gut Microbiota of Patients with Renal Failure.

Bifidobacteriaceae family are gut microbiota that exhibit probiotic or health promoting effects on the host. Several studies have suggested that gut microbiota are quantitatively and qualitatively altered in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The present study aimed to assess the members of Bifidobacteriaceae family in fecal samples of patients with CKD and ESRD and compare them with non-CKD/ESRD patients to find any changes in their counts and diversions in these patients. Twenty fresh fecal samples from patients with CKD/ESRD and twenty from non-CKD/ESRD patients were examined. Whole DNA was extracted from fecal samples and the gut microbiota composition was analyzed by next generation sequencing (NGS). A total of 651 strains were identified from 40 fecal samples, 8 (1.23%) strains of which were identified as family Bifidobacteriaceae. The most abundant species in both control and disease groups were Bifidobacterium adolescentis and Bifidobacterium longum subsp. longum, and the least abundant species in the disease group was Bifidobacterium animalis subsp. lactis. There was no significant difference in the abundance of various species between the disease and control groups (p &lt; 0.05). This study confirms that the members of the Bifidobacteriaceae family are not altered in patients with CKD/ESRD.

Bacillus subtilis HH2 ameliorates TNBS-induced colitis by modulating gut microbiota composition and improving intestinal barrier function in rabbit model

Inflammatory bowel disease (IBD) is known to cause inflammation, as well as intestinal flora and epithelial barrier dysfunction. We evaluated the function of Bacillus subtilis HH2 in a trinitrobenzenesulfonic acid (TNBS)-induced colitis rabbit model through the oral administration of this bacterium. Body weight, disease activity index (DAI) score, and histological changes in the rabbits were recorded. Colons were collected for ELISA, RT-PCR, and western blotting. Intestinal microflora were tested by 16S rRNA sequencing. Results showed that B. subtilis HH2 alleviated body weight loss and decreased the DAI and histological injury scores and also reduced the mRNA expression of TNF-α and IL-1β and enhanced the expression of IL-10. I n addition, B. subtilis HH2 promoted the expression of tight junction proteins, such as occludin, and the expression of related mRNA to maintain the intestinal mucosal barrier function to attenuate colitis symptoms in rabbits. By studying colonic microbiota, we observed that B. subtilis HH2 increased colonic microbial diversity after it was reduced due to TNBS administration; it also increased the relative abundance of the Bifidobacteriaceae family, but the abundances of Bacteroidetes and Proteobacteria were reduced. These results indicated that B. subtilis HH2 could decrease the severity of colitis induced by TNBS by regulating inflammatory cytokines, increasing tight junction proteins, and modulating intestinal microbiota. These findings suggest that the probiotic B. subtilis HH2 might prevent tissue damage due to colitis.

The Chronic Effect of Transgenic Maize Line with mCry1Ac or maroACC Gene on Ileal Microbiota Using a Hen Model.

The experiment was to determine the chronic effects of two transgenic maize lines that contained the mCry1Ac gene from the Bacillus thuringiensis strain (BT) and the maroACC gene from Agrobacterium tumefaciens strain (CC), respectively, on ileal microbiota of laying hens. Seventy-two laying hens were randomly assigned to one of the three dietary treatments for 12 weeks, as follows: (1) nontransgenic near-isoline maize-based diet (CT diet), (2) BT maize-based diet (BT diet), and (3) CC maize-based diet (CC diet). Ileum histological examination did not indicate a chronic effect of two transgenic maize diets. Few differences were observed in any bacterial taxa among the treatments that used high-throughput 16S rRNA gene sequencing. The only differences that were observed for bacterial genera were that Bifidobacterium belong within the Bifidobacteriaceae family tended to be greater (p = 0.114) abundant in hens fed the transgenic maize-based diet than in hens fed the CT diet. Birds that consumed the CC maize diet tended to have less abundance (p = 0.135) of Enterobacteriaceae family in the ileum than those that consumed the CT maize diet. These results indicate the lack of adverse effects of the BT maize and the CC maize lines on the ileal microbiota of hens for long term and provide important data regarding biosafety assessment of the transgenic maize lines.

The prevalence and transcriptional activity of the mucosal microbiota of ulcerative colitis patients

Active microbes likely have larger impact on gut health status compared to inactive or dormant microbes. We investigate the composition of active and total mucosal microbiota of treatment-naïve ulcerative colitis (UC) patients to determine the microbial picture at the start-up phase of disease, using both a 16S rRNA transcript and gene amplicon sequencing. DNA and RNA were isolated from the same mucosal colonic biopsies. Our aim was to identify active microbial members of the microbiota in early stages of disease and reveal which members are present, but do not act as major players. We demonstrated differences in active and total microbiota of UC patients when comparing inflamed to non-inflamed tissue. Several taxa, among them the Proteobacteria phyla and families therein, revealed lower transcriptional activity despite a high presence. The Bifidobacteriaceae family of the Actinobacteria phylum showed lower abundance in the active microbiota, although no difference in presence was detected. The most abundant microbiota members of the inflamed tissue in UC patients were not the most active. Knowledge of active members of microbiota in UC patients could enhance our understanding of disease etiology. The active microbial community composition did not deviate from the total when comparing UC patients to non-IBD controls.

Long-term intake of Lactobacillus paracasei KW3110 prevents age-related chronic inflammation and retinal cell loss in physiologically aged mice.

Age-related chronic inflammation is a major risk factor for the incidence and prevalence of age-related diseases, including infectious and neurodegenerative diseases. We previously reported that a lactic acid bacteria, Lactobacillus paracasei KW3110, activated macrophages and suppressed inflammation in mice and humans. In this study, we investigated whether long-term intake of heat-killed L. paracasei KW3110 modulated age-related inflammation and altered the gut microbiota in physiologically aged mice. Compared with age-matched control mice, fecal analyses of gut microbiota revealed that intake of L. paracasei KW3110 mitigated age-related changes of beneficial bacterial composition, including the Bifidobacteriaceae family. L. paracasei KW3110 intake also mitigated age-related immune defects by reducing the prevalence of interferon-gamma (IFN-γ) -producing inflammatory CD4-positive T cells in the lamina propia of the small intestine, and reduced serum levels of proinflammatory cytokines. Furthermore, L. paracasei KW3110 intake suppressed retinal inflammation by reducing proinflammatory cytokine-producing macrophage, and age-related retinal cell loss. Taken together, these findings suggested that L. paracasei KW3110 mitigated age-related chronic inflammation through modulation of gut microbiota composition and immune system functions in aged mice, and also reduced age-related retinal ganglion cell (RGC) loss. Further studies are needed to evaluate the effect in age-related senescent changes of the retina.

Comparative Genomics Reveals the Regulatory Complexity of Bifidobacterial Arabinose and Arabino-Oligosaccharide Utilization.

Members of the genus Bifidobacterium are common inhabitants of the human gastrointestinal tract. Previously it was shown that arabino-oligosaccharides (AOS) might act as prebiotics and stimulate the bifidobacterial growth in the gut. However, despite the rapid accumulation of genomic data, the precise mechanisms by which these sugars are utilized and associated transcription control still remain unclear. In the current study, we used a comparative genomic approach to reconstruct arabinose and AOS utilization pathways in over 40 bacterial species belonging to the Bifidobacteriaceae family. The results indicate that the gene repertoire involved in the catabolism of these sugars is highly diverse, and even phylogenetically close species may differ in their utilization capabilities. Using bioinformatics analysis we identified potential DNA-binding motifs and reconstructed putative regulons for the arabinose and AOS utilization genes in the Bifidobacteriaceae genomes. Six LacI-family transcriptional factors (named AbfR, AauR, AauU1, AauU2, BauR1 and BauR2) and a TetR-family regulator (XsaR) presumably act as local repressors for AOS utilization genes encoding various α- or β-L-arabinofuranosidases and predicted AOS transporters. The ROK-family regulator AraU and the LacI-family regulator AraQ control adjacent operons encoding putative arabinose transporters and catabolic enzymes, respectively. However, the AraQ regulator is universally present in all Bifidobacterium species including those lacking the arabinose catabolic genes araBDA, suggesting its control of other genes. Comparative genomic analyses of prospective AraQ-binding sites allowed the reconstruction of AraQ regulons and a proposed binary repression/activation mechanism. The conserved core of reconstructed AraQ regulons in bifidobacteria includes araBDA, as well as genes from the central glycolytic and fermentation pathways (pyk, eno, gap, tkt, tal, galM, ldh). The current study expands the range of genes involved in bifidobacterial arabinose/AOS utilization and demonstrates considerable variations in associated metabolic pathways and regulons. Detailed comparative and phylogenetic analyses allowed us to hypothesize how the identified reconstructed regulons evolved in bifidobacteria. Our findings may help to improve carbohydrate catabolic phenotype prediction and metabolic modeling, while it may also facilitate rational development of novel prebiotics.

Comparative genomic and phylogenomic analyses of the Bifidobacteriaceae family

BackgroundMembers of the Bifidobacteriaceae family represent both dominant microbial groups that colonize the gut of various animals, especially during the suckling stage of their life, while they also occur as pathogenic bacteria of the urogenital tract. The pan-genome of the genus Bifidobacterium has been explored in detail in recent years, though genomics of the Bifidobacteriaceae family has not yet received much attention. Here, a comparative genomic analyses of 67 Bifidobacteriaceae (sub) species including all currently recognized genera of this family, i.e., Aeriscardovia, Alloscardovia, Bifidobacterium, Bombiscardovia, Gardnerella, Neoscardovia, Parascardovia, Pseudoscardovia and Scardovia, was performed. Furthermore, in order to include a representative of each of the 67 (currently recognized) (sub) species belonging to the Bifidobacteriaceae family, we sequenced the genomes of an additional 11 species from this family, accomplishing the most extensive comparative genomic analysis performed within this family so far.ResultsPhylogenomics-based analyses revealed the deduced evolutionary pathway followed by each member of the Bifidobacteriaceae family, highlighting Aeriscardovia aeriphila LMG 21773 as the deepest branch in the evolutionary tree of this family. Furthermore, functional analyses based on genome content unveil connections between a given member of the family, its carbohydrate utilization abilities and its corresponding host. In this context, bifidobacterial (sub) species isolated from humans and monkeys possess the highest relative number of acquired glycosyl hydrolase-encoding genes, probably in order to enhance their metabolic ability to utilize different carbon sources consumed by the host.ConclusionsWithin the Bifidobacteriaceae family, genomics of the genus Bifidobacterium has been extensively investigated. In contrast, very little is known about the genomics of members of the other eight genera of this family. In this study, we decoded the genome sequences of each member of the Bifidobacteriaceae family. Thanks to subsequent comparative genomic and phylogenetic analyses, the deduced pan-genome of this family, as well as the predicted evolutionary development of each taxon belonging to this family was assessed.

In vitro and in vivo evaluation of the probiotic attributes of Lactobacillus kefiranofaciens XL10 isolated from Tibetan kefir grain.

Lactobacillus kefiranofaciens XL10, with a high yield of extracellular polysaccharide (EPS), is isolated from Tibetan kefir grain and benefits the health of human beings and has been considered to exhibit probiotic potential in vitro and in vivo. The probiotic function of the strain was studied extensively, viz., acid and bile salt tolerances, cell surface hydrophobicity and autoaggregation, the modulation of gut microbiota, and the distribution and colonization of XL10 in the mouse intestinal tract after oral administration. XL10 could survive 3-h incubation at pH3.5 and exhibited cell surface hydrophobicity of ∼79.9% and autoaggregation of ∼27.8%. After continuous oral administration of XL10 for 2weeks, the Bifidobacteriaceae family increased, accompanied by an observable decline in Proteobacteria phyla in the tested mice. Butyrivibrio and Pseudobutyrivibrio, recognized as butyric acid-producing bacteria, could also be detected at day 7 and day 14, respectively. The most abundant community in the mouse gut had formed by day 14. Additionally, we found that XL10 successfully adhered to the mucous tissue and colonized the ileum of the mice based on fluorescence imaging, flow cytometry, and qPCR. Our results suggested that XL10 has excellent probiotic properties and represents an alternative for exploitation in the development of novel functional foods.