Genus Bifidobacterium Research Articles

The Relationship Between Diet, Gut Microbiota, and Serum Metabolome of South Asian Infants at 1 Year

BackgroundDiet is known to affect the gut microbiota and the serum metabolome in adults, but this has not been fully explored in infants. Infancy is an important developmental period that may influence a person’s long-term health. Infant development can be affected by diet, which also interacts with the developing gut microbiota. ObjectivesThis study aimed to explore the associations between diet, the gut microbiota, and the serum metabolome of 1-y-old infants with the overarching goal of identifying serum biomarkers of diet and/or the gut microbiota. MethodsWe derived dietary patterns of 1-y-old infants (n = 182) participating in the Canadian South Asian Birth Cohort (START) study. We compared gut microbiota α-diversity and β-diversity and taxa relative abundance from 16S rRNA gene profiles with dietary patterns (PERMANOVA, Envfit) and investigated diet–serum metabolite associations using a multivariate analysis (partial least squares–discriminant analysis) and univariate analysis (t test). We explored the effect of nondietary factors on diet–serum metabolite relationships by incorporating diet, the gut microbiota, and maternal, perinatal, and infant characteristics in a multivariable forward stepwise regression. We replicated this analysis in White European infants, from the CHILD Cohort Study (n = 81). ResultsA dietary pattern characterized by formula consumption and negatively associated with breastfeeding most strongly predicted variation in the gut microbiota (R2 = 0.109) and serum metabolome (R2 = 0.547). Breastfed participants showed higher abundance of microbes from the genera Bifidobacterium (3.29 log2-fold) and Lactobacillus (7.93 log2-fold) and higher median concentrations of the metabolites S-methylcysteine (1.38 μM) and tryptophan betaine (0.43 μM) than nonbreastfed participants. Formula consuming infants showed higher median concentrations of branched-chain/aromatic amino acids (average 48.3 μM) than non–formula-consuming infants. ConclusionsFormula consumption and breastfeeding most strongly predicted the serum metabolites of 1-y-old infants, even when the gut microbiota, solid food consumption, and other covariates were considered.

Multi-omics reveals specific host metabolism-microbiome associations in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, but effective prevention and treatment strategies are lacking. Recently, gut microbiome and its metabolitesis are considered to be an influencing factor of stroke. However, little is known about the effects of the gut microbiome on ICH and host metabolic activity. Therefore, we used 16S sequencing, macrogenomics sequencing and untargeted metabolomics to explore the differences in gut microbial-metabolome interactions between patients with intracerebral hemorrhage and healthy control populations. We found a significant decrease in the phylum of Firmicutes and a significant increase of Bacteroidetes in ICH patients. At the genus level, Streptococcus, Bifidobacterium, Akkermansia, and Lactobacillus were more abundant in ICH patients. Macrogenomic analysis revealed active glycosaminoglycan degradation, heme synthesis, galactose degradation, lipopolysaccharide core region synthesis, and beta-Lactam resistance in ICH patients. Serum untargeted metabolomic analysis combined with ROC curves showed that octanoylcarnitine, decanoylcarnitine, dodecanoylcarnitine, glyceric acid, pyruvic acid, aspartic acid, methylcysteine, pyroglutamic acid, 9E-tetradecenoic acid, N-Acetylneuraminic acid, and aconitic acid were the best markers for the diagnosis of ICH. Correlation analysis showed that microbiome enriched in the gut of ICH patients were significantly correlated with serum metabolites, revealing a close correlation between the gut microbiome of ICH patients and the host metabolome, and significant differences from the healthy population. microbiota-host co-metabolites including pyruvic acid and 9E-tetradecenoic acid is associated with the the National Institutes of Health Stroke Scale (NIHSS) scores. In conclusion, microbiome-related metabolites in ICH patients was associated with the severity of ICH, the microbiota-host co-metabolites may be a potential may be potential therapeutic targets.

Vitamin C improves gut Bifidobacteria in humans.

Aims: Numerous beneficial effects of vitamin C (ascorbic acid) supplementation have been reported in the literature. However, data on its effects toward the gut microbiome are limited. We assessed the effect of vitamin C supplementation on the abundance of beneficial bacterial species in the gut microbiome. Materials and methods: Stool samples were analyzed for relative abundance of gut microbiome bacteria using next-generation sequencing-based profiling and metagenomic shotgun analysis. Results: Supplementation with vitamin C increased the abundance of bacteria of the genus Bifidobacterium (p=0.0001) and affected various species. Conclusion: The beneficial effects of vitamin C supplementation may be attributed to modulation of the gut microbiome and the consequent health benefits thereof.

The correlation of the fecal microbiome with the biochemical profile during menopause: a Brazilian cohort study

BackgroundHormonal, biochemical, and metabolic changes after menopause may alter the quality of life of women, leading to vasomotor, psychological, and genitourinary symptoms, and changes in their gut microbiota, which regulates estrogen levels through the estroboloma. Fecal samples were used to investigate the changes in the gut microbiota during aging and hormonal changes in women. A balanced gut microbiota has been associated with health or disease conditions and remains poorly understood after menopause. This study identified the fecal microbiota, and their association with biochemical and hormonal parameters of a cohort of women in the climacteric in the city of Ouro Preto—MG, Brazil.MethodsA total of 102 women aged 40 to 65 years old were recruited and distributed into three groups according to the STRAW criteria for reproductive stage: reproductive (n = 18), premenopausal (n = 26), and postmenopausal (n = 58). Blood samples were collected to measure their serum biochemical and hormone levels, and the participants answered a questionnaire. The gut microbiota was analyzed from fecal samples by qPCR using the genera Bifidobacterium, Bacteroides, Lactobacillus, and Clostridium.ResultsThe following parameters showed differences among the groups: total cholesterol, triglycerides, VLDL, ApoB, urea, calcium, uric acid, and alkaline phosphatase (p < 0.05). qPCR revealed the genus Clostridium to be the most abundant in all three groups. In the reproductive age group, the significant correlations were: Bacteroides with glucose (r = -0.573 p = 0.0129), and SDHEA (r = -0.583 p = 0.0111). For the premenopausal group, they were: Bifidobacteria with total cholesterol (r = 0.396 p = 0.0451), LDL (r = 0.393 p = 0.0468), ApoB (r = 0.411 p = 0.0368); Lactobacillus and calcium (r = 0.443 p = 0.0232), ALP (r = 0.543 p = 0.0041), LPa (r =-0.442 p = 0.02336); and Bacteroides and urea (r =-0.461 p = 0.0176). In the postmenopausal group, they were Bifidobacterium and ALP (r =-0.315 p = 0.0159), Lactobacillus and urea (r =-0.276 p = 0.0356), and Clostridium and beta estradiol (r =-0.355 p = 0.0062).ConclusionIn conclusion, the hormonal and metabolic changes during menopause in the population studied were accompanied by a significant change in the fecal microbiota, especially of the genus Clostridium.

QseC sensor kinase modulates the human microbiota during enterohemorrhagic Escherichia coli O157:H7 infection in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®).

Enterohemorrhagic Escherichia coli (EHEC) is an important gastrointestinal pathogen known for its ability to cause hemorrhagic colitis and induce hemolytic-uremic syndrome. The inner membrane QseC histidine kinase sensor has shown to be an important regulator of the locus of enterocyte effacement (LEE) island, where important EHEC key virulence genes are located. However, the QseC role during EHEC infection in human microbiota remains unknown. Herein, using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), we investigated whether the QseC sensor has a role in human microbiota modulation by EHEC in a dynamic model. Our data demonstrated that the QseC sensor modulates human microbiota during EHEC infection, and its absence leads to an increase in Lactobacillaceae and Bifidobacterium genus predominance, although non-effect on Bacteroides genus by EHEC strains was observed. In co-culture, the Lactobacillus acidophilus has affected EHEC growth and impaired the EHEC growth under space-niche competition, although no growth difference was observed in the QseC sensor presence. Also, differences in EHEC growth were not detected in competition with Bacteroides thetaiotaomicron and EHEC strains did not affect B. thetaiotaomicron growth either. When investigating the mechanisms behind the SHIME results, we found that hcp-2 expression for the type 6 secretion system, known to be involved in bacterial competition, is under QseC sensor regulation beneath different environmental signals, such as glucose and butyrate. Our findings broaden the knowledge about the QseC sensor in modulating the human microbiota and its importance for EHEC pathogenesis.

Leuconostoc mesenteroides CJNU 0147 균주를 적용한 발효 자몽추출물의 장내 유해세균 억제 및 비피도박테리아 증식 효과

Grapefruit extract rich in functional substances adjusting pH 5.0 and adding sucrose (final concentration, 2%) was fermented by Leuconostoc mesenteroides CJNU 0147 strain, consequently prepared a fermented grapefruit extract containing dextran. As a result of analyzing the growth inhibitory effect on gut harmful bacterium Clostridium difficile strain using the prepared fermented grapefruit extract, the viable cell count was significantly reduced (p&lt;0.05 vs. control for 0.5 brix as a final concentration; p&lt;0.001 vs. control for 1.0 brix). On the other hand, the proliferative ability of the extract for Bifidobacterium breve strain, which is one of the species of the genus Bifidobacterium well known as human gut beneficial bacteria, was confirmed (p&lt;0.001 vs. control for both 0.5 and 1.0 brix). These results indicate fermented grapefruit extract with Leu. mesenteroides CJNU 0147 strain inhibits the growth of gut harmful bacterium C. difficile and promotes the proliferation of beneficial bacterium B. breve and is expected to be used as a functional food material for gut health.

Remodeling of the microbiota improves the environmental adaptability and disease resistance in Tibetan pigs.

The establishment of intestinal microbiota and the maintenance of its equilibrium structure plays an important role in Tibetan pigs during different growth stages. Understanding the structure and function of the intestinal microbiota at different growth stages of Tibetan pigs can provide a theoretical basis for guiding nutritional regulation and feeding management in different stages. Fecal samples were collected from the Tibetan piglets at different growth stages, and the 16S rRNA was sequenced to analyze the changes of intestinal microbiota. Alpha and Beta diversity indexes showed that the diversity of the intestinal microbiota did not change during the three growth stages, and the main components of intestinal microbiota were not significantly different. At the phylum level, Firmicutes and Bacteroidetes were dominant and abundant at different growth stages and were not restricted by age. At the genus level, Streptococcus, Lactobacillus, and Bifidobacterium were the most dominant in the TP10d and TP40d groups, Streptococcus was the most dominant in the TP100d group, followed by Treponema_2 and Lactobacillus. Fusobacteria, Gluconobacter, and Synergistetes were found to be specific genera of 10-day-old Tibetan piglets by LEfSe combined with LDA score. The change of diet made Tenericutes and Epsilonbacteraeota, which are closely related to digestive fiber, become specific bacteria at the age of 40 days. With the consumption of oxygen in the intestine, obligate anaerobes, such as Verrucomicrobia, Fibrobacter, and Planctomycetes, were the characteristic genera of 100 days. KEGG function prediction analysis showed that the intestinal microbiota function of Tibetan pigs changed dynamically with the growth and development of Tibetan piglets. In conclusion, the structure and composition of the intestinal microbiota of Tibetan pigs are significantly different at different growth and development stages, which plays an important role in their immune performance.

Bifidobacterium longum, Lactobacillus plantarum and Pediococcus acidilactici Reversed ETEC-Inducing Intestinal Inflammation in Mice.

Microecological preparation could relieve Enterotoxigenic Escherichia coli (ETEC) K88-induced diarrhea in piglets, but which bacteria play a key role and the mitigation mechanism have not been fully clarified. In this study, 36 male mice were randomly divided into six groups (CON, K88, BK (Bifidobacterium longum + K88), LK (Lactobacillus plantarum + K88), PK (Pediococcus acidilactici + K88), and MK (mixed strains + K88)) to explore the prevention mechanisms. Three probiotic strains and their mixtures (TPSM) significantly relieved the weight loss and restored the ratio of villus height to crypt depth in the jejunum. Except for Bifidobacterium longum, other strains significantly decreased interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in mice serum. The TPSM treatment significantly downregulated the mRNA expression of the inflammatory cytokines and the Toll-like receptor and downstream gene (TLR4, MyD88, NF-κB) in jejunum induced by ETEC. Furthermore, the TPSM could restore dysbiosis of the intestinal microbiota caused by ETEC. The intestinal microbiota analysis demonstrated that Bifidobacterium longum enriched the Bifidobacterium genus (p < 0.05), Lactobacillus plantarum enriched the Lactobacillus genus (p < 0.05), Pediococcus acidilactici enriched the Coriobacteriaceae_UCG-002 and Christensenellaceae_R-7_group genus (p < 0.05), mixed bacteria enriched the Akkermansia genus (p < 0.05), but ETEC enriched the Desulfovibrio genus (p < 0.05). Meanwhile, the starch and sucrose metabolism, galactose and fructose metabolism, mannose metabolism and ABC transporters were increased with probiotics pre-treatment (p < 0.05). To sum up, the microecological preparation alleviated ETEC-induced diarrhea by regulating the immune response, rebalancing intestinal microbiota and improving carbohydrate metabolism.

Dihydromyricetin Enhances Exercise-Induced GLP-1 Elevation through Stimulating cAMP and Inhibiting DPP-4.

The purpose of this study was to examine whether endogenous GLP-1 (glucagon-like peptide-1) could respond to exercise training in mice, as well as whether dihydromyricetin (DHM) supplementation could enhance GLP-1 levels in response to exercise training. After 2 weeks of exercise intervention, we found that GLP-1 levels were significantly elevated. A reshaped gut microbiota was identified following exercise, as evidenced by the increased abundance of Bifidobacterium, Lactococcus, and Alistipes genus, which are involved in the production of short-chain fatty acids (SCFAs). Antibiotic treatment negated exercise-induced GLP-1 secretion, which could be reversed with gut microbiota transplantation. Additionally, the combined intervention (DHM and exercise) was modeled in mice. Surprisingly, the combined intervention resulted in higher GLP-1 levels than the exercise intervention alone. In exercised mice supplemented with DHM, the gut microbiota composition changed as well, while the amount of SCFAs was unchanged in the stools. Additionally, DHM treatment induced intracellular cAMP in vitro and down-regulated the gene and protein expression of dipeptidyl peptidase-4 (DPP-4) both in vivo and in vitro. Collectively, the auxo-action of exercise on GLP-1 secretion is associated with the gut-microbiota-SCFAs axis. Moreover, our findings suggest that DHM interacts synergistically with exercise to enhance GLP-1 levels by stimulating cAMP and inhibiting DPP-4.

Effect of natural polyphenols in Chinese herbal medicine on obesity and diabetes: Interactions among gut microbiota, metabolism, and immunity.

With global prevalence, metabolic diseases, represented by obesity and type 2 diabetes mellitus (T2DM), have a huge burden on human health and medical expenses. It is estimated that obese population has doubled in recent 40 years, and population with diabetes will increase 1.5 times in next 25 years, which has inspired the pursuit of economical and effective prevention and treatment methods. Natural polyphenols are emerging as a class of natural bioactive compounds with potential beneficial effects on the alleviation of obesity and T2DM. In this review, we investigated the network interaction mechanism of "gut microbial disturbance, metabolic disorder, and immune imbalance" in both obesity and T2DM and systemically summarized their multiple targets in the treatment of obesity and T2DM, including enrichment of the beneficial gut microbiota (genera Bifidobacterium, Akkermansia, and Lactobacillus) and upregulation of the levels of gut microbiota-derived metabolites [short-chain fatty acids (SCFAs)] and bile acids (BAs). Moreover, we explored their effect on host glucolipid metabolism, the AMPK pathway, and immune modulation via the inhibition of pro-inflammatory immune cells (M1-like Mϕs, Th1, and Th17 cells); proliferation, recruitment, differentiation, and function; and related cytokines (TNF-α, IL-1β, IL-6, IL-17, and MCP-1). We hope to provide evidence to promote the clinical application of natural polyphenols in the management of obesity and T2DM.

Effect of 30 days of ketogenic Mediterranean diet with phytoextracts on athletes' gut microbiome composition.

Recent research suggest that gut microbiome may play a fundamental role in athlete's health and performance. Interestingly, nutrition can affect athletic performance by influencing the gut microbiome composition. Among different dietary patterns, ketogenic diet represents an efficient nutritional approach to get adequate body composition in athletes, however, some concerns have been raised about its potential detrimental effect on gut microbiome. To the best of our knowledge, only one study investigated the effect of ketogenic diet on the gut microbiome in athletes (elite race walkers), whilst no studies are available in a model of mixed endurance/power sport such as soccer. This study aimed to investigate the influence of a ketogenic Mediterranean diet with phytoextracts (KEMEPHY) diet on gut microbiome composition in a cohort of semi-professional soccer players. 16 male soccer players were randomly assigned to KEMEPHY diet (KDP n = 8) or western diet (WD n = 8). Body composition, performance measurements and gut microbiome composition were measured before and after 30 days of intervention by 16S rRNA amplicon sequencing. Alpha-diversity measures and PERMANOVA was used to investigate pre-post differences in the relative abundance of all taxonomic levels (from phylum to genus) and Spearman's correlations was used to investigate associations between microbial composition and macronutrient intake. Linear discriminant analysis was also performed at the different taxonomic levels on the post-intervention data. No differences were found between pre and post- dietary intervention for microbial community diversity: no significant effects of time (p = 0.056, ES = 0.486 and p = 0.129, ES = 0.388, respectively for OTUs number and Shannon's ENS), group (p = 0.317, ES = 0.180 and p = 0.809, ES = 0.047) or time × group (p = 0.999, ES = 0.01 and p = 0.230, ES = 0.315). Post-hoc paired Wilcoxon test showed a significant time × group effect for Actinobacteriota (p = 0.021, ES = 0.578), which increased in the WD group (median pre: 1.7%; median post: 2.3%) and decreased in the KEMEPHY group (median pre: 4.3%; median post: 1.7%). At genus level, the linear discriminant analysis in the post intervention differentiated the two groups for Bifidobacterium genus (pertaining to the Actinobacteria phylum), Butyricicoccus and Acidaminococcus genera, all more abundant in the WD group, and for Clostridia UCG-014 (order, family, and genus), Butyricimonas, Odoribacterter genera (pertaining to the Marinifilaceae family), and Ruminococcus genus, all more abundant in the KEMEPHY group. Our results demonstrate that 30 days of KEMEPHY intervention, in contrast with previous research on ketogenic diet and gut microbiome, do not modify the overall composition of gut microbiome in a cohort of athletes. KEMEPHY dietary pattern may represent an alternative and safety tool for maintaining and/or regulating the composition of gut microbiome in athletes practicing regular exercise. Due to the fact that not all ketogenic diets are equal, we hypothesized that each version of ketogenic diet, with different kind of nutrients or macronutrients partitioning, may differently affect the human gut microbiome.

Fecal microbiota composition is related to brown adipose tissue 18F-fluorodeoxyglucose uptake in young adults

ObjectiveHuman brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and its related cardiometabolic diseases; however, whether the gut microbiota might be an efficient stimulus to activate BAT metabolism remains to be ascertained. We aimed to investigate the association of fecal microbiota composition with BAT volume and activity and mean radiodensity in young adults.Methods82 young adults (58 women, 21.8 ± 2.2 years old) participated in this cross-sectional study. DNA was extracted from fecal samples and 16S rRNA sequencing was performed to analyse the fecal microbiota composition. BAT was determined via a static 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography scan (PET/CT) after a 2 h personalized cooling protocol. 18F-FDG uptake was also quantified in white adipose tissue (WAT) and skeletal muscles.ResultsThe relative abundance of Akkermansia, Lachnospiraceae sp. and Ruminococcus genera was negatively correlated with BAT volume, BAT SUVmean and BAT SUVpeak (all rho ≤ − 0.232, P ≤ 0.027), whereas the relative abundance of Bifidobacterium genus was positively correlated with BAT SUVmean and BAT SUVpeak (all rho ≥ 0.262, P ≤ 0.012). On the other hand, the relative abundance of Sutterellaceae and Bifidobacteriaceae families was positively correlated with 18F-FDG uptake by WAT and skeletal muscles (all rho ≥ 0.213, P ≤ 0.042). All the analyses were adjusted for the PET/CT scan date as a proxy of seasonality.ConclusionOur results suggest that fecal microbiota composition is involved in the regulation of BAT and glucose uptake by other tissues in young adults. Further studies are needed to confirm these findings.Clinical trial informationClinicalTrials.gov no. NCT02365129 (registered 18 February 2015).

Pan-genome evolution and its association with divergence of metabolic functions in Bifidobacterium genus.

Previous studies were mainly focused on genomic evolution and diversity of type species of Bifidobacterium genus due to their health-promoting effect on host. However, those studies were mainly based on species-level taxonomic resolution, adaptation, and characterization of carbohydrate metabolic features of the bifidobacterial species. Here, a comprehensive analysis of the type strain genome unveils the association of pan-genome evolution with the divergence of metabolic function of the Bifidobacterium genus. This study has also demonstrated that horizontal gene transfer, as well as genome expansion and reduction events, leads to the divergence of metabolic functions in Bifidobacterium genus. Furthermore, the genome-based search of probiotic traits among all the available bifidobacterial type strains gives hints on type species, that could confer health benefits to nutrient-deficient individuals. Altogether, the present study provides insight into the developments of genomic evolution, functional divergence, and potential probiotic type species of the Bifidobacterium genus.

Designation of optimal reference strains representing the infant gut bifidobacterial species through a comprehensive multi-omics approach.

The genomic era has resulted in the generation of a massive amount of genetic data concerning the genomic diversity of bacterial taxa. As a result, the microbiological community is increasingly looking for ways to define reference bacterial strains to perform experiments that are representative of the entire bacterial species. Despite this, there is currently no established approach allowing a reliable identification of reference strains based on a comprehensive genomic, ecological, and functional context. In the current study, we developed a comprehensive multi-omics approach that will allow the identification of the optimal reference strains using the Bifidobacterium genus as test case. Strain tracking analysis based on 1664 shotgun metagenomics datasets of healthy infant faecal samples were employed to identify bifidobacterial strains suitable for in silico and in vitro analyses. Subsequently, an ad hoc bioinformatic tool was developed to screen local strain collections for the most suitable species-representative strain alternative. The here presented approach was validated using in vitro trials followed by metagenomics and metatranscriptomics analyses. Altogether, these results demonstrated the validity of the proposed model for reference strain selection, thus allowing improved in silico and in vitro investigations both in terms of cross-laboratory reproducibility and relevance of research findings.

Efficacy of probiotics for the treatment of irritable bowel syndrome

A review of current literature data was made, substantiating the high prevalence and social significance of irritable bowel syndrome (IBS). In different regions of the world, the prevalence of IBS ranges from 10% to 15%. The pathogenesis of IBS is a multifactorial process, including dysmotility, sluggish immune inflammation, changes in intestinal permeability, dysbiosis, exposure to infectious agents, malnutrition, neurohumoral dysregulation, changes in the central nervous system (psychological stress, cognitive dysfunction) in combination with genetic factors. The complexity of the pathogenesis determines the heterogeneity of the clinical manifestations of IBS, among which there may be forms with a predominance of pain, constipation, diarrhea, flatulence, which in turn complicates approaches to the treatment of this disease. The decisive importance of fecal dysbiosis for the pathogenesis of functional bowel pathology is now recognized. A 2019 systematic review showed a clear decrease in the genera Bifidobacterium and Faecalibacterium, an increase in the families Lactobacillaceae, Enterobacteriaceae and the genus Bacteroides in patients with IBS compared with healthy individuals. The Rome IV criteria, the recommendations of the British Society of Gastroenterology, the United European Gastroenterology and the European Society for Neurogastroenterology and Motility, the Russian Gastroenterological Association substantiate the use of probiotics for the treatment of IBS. Placebo-controlled clinical studies confirm the action of Bifidobacterium longum 35624 to normalize the frequency and form of stools, relieve general symptoms, abdominal pain, bloating, and improve the quality of life in patients with IBS. The expert council, held on March 18, 2022 in Moscow, chaired by the chief gastroenterologist of the Ministry of Health of the Russian Federation, Academician of the RAS V.T. Ivashkin, confirmed the effectiveness of probiotics for the treatment of IBS.

Changes in the gut bacteriome upon gluten-free diet intervention do not mediate beta cell preservation.

We previously detected indications that beta cell function is protected by gluten-free diet (GFD) introduced shortly after the onset of childhood type 1 diabetes. The present aim was to assess whether GFD was associated with changes in the gut bacteriome composition and in its functional capacity, and whether such changes mediated the observed effects of GFD on beta cell function. Forty-five children (aged 10.2 ± 3.3 years) were recruited into a self-selected intervention trial primarily focused on determining the role of GFD on beta cell preservation ( ClinicalTrials.gov NCT02867436). Stool samples were collected prior to the dietary intervention and then at 3-month intervals. A total of 128 samples from the GFD group and 112 from the control group were analysed for bacteriome 16S rDNA community profiles, the bacteriome functional capacity was predicted using PICRUSt2 and actual gut metabolome profiles measured using NMR. Intestinal permeability was assessed using serum zonulin concentrations at 1, 6 and 12 months and lactulose/mannitol tests at the end of intervention. Dietary questionnaires were used to ensure that the dietary intervention did not result in differences in energy or nutrient intake. The bacteriome community composition changed during the intervention with GFD: of abundant genera, a 3.3-fold decrease was noted for Bifidobacterium genus (adjusted p=1.4 × 10-4 in a DESeq2 model, p=0.026 in generalised estimating equations model), whereas a 2.4-fold increase was observed in Roseburia (adjusted p=0.02 in DESeq2 model, p=0.002 in generalised estimating equations model). The within-sample (alpha) diversity did not change, and there was no statistically significant clustering of GFD samples in the ordination graphs of beta diversity. Neither of the genera changes upon GFD intervention showed any association with the pace of beta cell loss (p>0.50), but of the remaining taxa, several genera of Bacteroidaceae family yielded suggestive signals. The faecal metabolome profile ordination correlated with that of bacteriomes but did not associate with GFD or categories of beta cell preservation. There was no indication of changes in gut permeability. The bacteriome reacted to GFD, but the changes were unrelated to the pace of beta cell capacity loss. The previously observed moderately protective effect of GFD is therefore mediated through other pathways.

Exploring the biodiversity of Bifidobacterium asteroides among honey bee microbiomes.

Bifidobacterium asteroides is considered the ancestor of the genus Bifidobacterium, which has evolved in close touch with the hindgut of social insects. However, recent studies revealed high intraspecies biodiversity within this taxon, uncovering the putative existence of multiple bifidobacterial species, thus, suggesting its reclassification. Here, a genomic investigation of 98 B. asteroides-related genomes retrieved from public repositories and reconstructed from metagenomes of the hindgut of Apis mellifera and Apis cerana was performed to shed light on the genetic variability of this taxon. Phylogenetic and genomic analyses revealed the existence of eight clusters, of which five have been recently characterized with a representative type strain of the genus and three were represented by putative novel bifidobacterial species inhabiting the honeybee gut. Then, the dissection of 366 shotgun metagenomes of honeybee guts revealed a pattern of seven B. asteroides-related taxa within A. mellifera that co-exist with the host, while A. cerana microbiome was characterized by the predominance of one of the novel species erroneously classified as B. asteroides. A further glycobiome analysis unveiled a conserved repertoire of glycosyl hydrolases (GHs) reflecting degradative abilities towards a broad range of simple carbohydrates together with genes encoding specific GHs of each B. asteroides-related taxa.

S551 Loss of Bifidobacteria in Lyme Disease: Cause or Effect

Introduction: Lyme disease is a poorly understood condition which starts with a rash but may continue with chronic fatigue and neurological symptoms. Approximately 1 in 5 early Lyme disease patients have GI symptoms, such as nausea, anorexia, abdominal pain, or diarrhea. Lyme disease is thought to be cased by microbes in the spirochetes phylum transmitted by black legged ticks. Lyme-related healthcare costs in America exceed 1.3 billion dollars annually. Bifidobacteria are known for their beneficial probiotic actions within the human gut microbiome. Their numbers are reduced in severe COVID-19, Clostridioides difficile infection and Inflammatory Bowel Disease. To our knowledge Bifidobacteria levels have not been studied in Lyme disease patients. Given the importance of Bifidobacterium abundance in other diseases, we focused on relative abundance of Bifidobacterium in fecal samples of patients with Lyme disease compared to controls. Methods: Fecal samples were assessed for relative abundance of Bifidobacterium in Healthy Control subjects without Lyme disease (n=20) compared to patients with Lyme disease (n=39). The average symptom duration in patients with Lyme disease was 5 years and none were on antibiotics 2 weeks prior to sample collection (range of symptoms from 1 month to 20 years, all treated initially with antibiotics).Metagenomics Next Generation sequencing was performed on fecal samples, where DNA samples were extracted and normalized for library downstream analysis using Shotgun Methodology. Mann-Whitney Statistical test was used for comparison. This study was IRB approved. Results: Relative Abundance of bifidobacteria was significantly decreased (p< 0.0001) in patients with Lyme disease. Median and interquartile range (IQR) were: Control (Median:4.175%; IQR:1.72-10.27%) and Lyme disease (Median:0.0014%; IQR:0.00%-0.96%)(Figure). 30/39 Lyme disease patients (77%) were found to possess < 1% relative abundance of Bifidobacterium in their stool sample. Of interest only 1/39 samples showed presence of Spirochetes in stool samples. Conclusion: This is the first study that demonstrates low levels of Bifidobacteria in patients with chronic Lyme disease. These results raise three questions; whether the disease was caused by 1. the original microbe creating loss of Bifidobacterium 2. baseline low Bifidobacteria due likely to either diet or medications or 3. excessive treatment. Given Lyme disease comprises a gut dysbiosis issue, therapies should also aim at restoration of depleted Bifidobacteria.Figure 1.: Lyme disease subjects have significantly (p<0.001) reduced relative abundance of genus bifidobacterium.

The Potential Benefits and Controversies of Probiotics Use in Patients at Different Stages of Chronic Kidney Disease.

The therapeutic modulation of the gut microbiome has been suggested to be one of the tools in the integrated management of chronic kidney disease (CKD) in recent years. Lactobacillus and Bifidobacterium genera are the two most commonly used probiotics strains. Most of the probiotics used in studies are mixed formulation. There is no consensus on the dose and duration of the probiotic administration for CKD patients Increasing evidence indicates that patients with early stage (1–2) CKD have an altered quantitative and qualitative microbiota profile. However, there was a dearth of prospective controlled studies on the use of probiotics in the early stage of the CKD population. The association between gut microbiota disturbance and advanced CKD was reported. Most randomized controlled trials on probiotic treatment used in CKD stage 3–5ND patients reported positive results. The metabolites of abnormal gut microbiota are directly involved in the pathogenetic mechanisms of cardiovascular disease and inflammation. We summarized 13 studies performed in the dialysis population, including 10 in hemodialysis (HD) patients and 3 in peritoneal dialysis (PD). Some controversial results were concluded on the decreasing plasma concentration of uremic toxin, symptoms, inflammation, and cardiovascular risk. Only three randomized controlled trials on PD were reported to show the potential beneficial effects of probiotics on inflammation, uremic toxins and gastrointestinal symptoms. There is still no standard in the dosage and duration of the use of probiotics in CKD patients. Overall, the probiotic administration may have potential benefit in improving symptoms and quality of life, reducing inflammation, and delaying the progression of kidney failure. Further research studies using a larger sample size with longer follow-up durations and a greater focus on clinical outcomes—including survival—are warranted to elucidate the significant clinical impact of the use of probiotics in CKD patients.

Selenium-Enriched Black Soybean Protein Prevents Benzo(a)pyrene-Induced Pyroptotic Colon Damage and Gut Dysbacteriosis.

Selenium-enriched black soybean protein (SeBSP) is a kind of high-quality selenium resource with many physiological functions. Benzo(a)pyrene (BaP) is a well-known injurant that widely exists in high-temperature processed food and has been previously found to cause colon injury. In this study, the effects of SeBSP on colonic damage induced by BaP in BALB/C mice were investigated by comparing it with normal black soybean protein (BSP). SeBSP inhibited the BaP-induced reductions on body weight, food intake, and water intake. Moreover, metabolic enzymes, including AhR, CYP1A1, CYP1B1, and GST-P1, that were promoted by BaP were downregulated by SeBSP, reducing oxidative damage caused by BaP in the metabolic process. The classical pyroptosis indexes (i.e., NLRP3, ASC, Caspase-1, GSDMD) and inflammatory factors (i.e., TNF-α, IL-1β, IL-18, iNOS, COX-2) were downregulated by SeBSP in BaP-treated mice, suggesting the benefits of SeBSP in reducing colonic toxicity. Notably, SeBSP enhanced microbial diversity of gut microbiota and increased relative abundances of prebiotic bacteria, for example, Lactobacillus reuteri, Bacteroides thetaiotaomicron, and genera Bifidobacterium, and Blautia, along with the promotion of short-chain fatty acids. Integrative analysis showed strong links between the antioxidant and anti-inflammatory effects of SeBSP and its altered gut microbiota. Collectively, our study demonstrates the pronounced benefits of Se-enriched black soybean in preventing the colonic toxicity of BaP, and such effects could be mediated by gut microbiota.