Parabacteroides Distasonis Research Articles

Intermittent fasting promotes repair of rotator cuff injury in the early postoperative period by regulating the gut microbiota.

BackgroundThe repair of rotator cuff injury is affected by lifestyle and metabolic factors. Intermittent fasting (IF) can promote repair of damaged tissue by regulating intestinal flora, which provides an idea of therapy for rotator cuff injury. The aim of this study was to investigate the effects of fasting on rotator cuff repair after injury, and the role of intestinal flora or a single strain in this process.MethodsMice underwent rotator cuff injury were treated with intermittent fasting or fed ad libitum. Fasting began one month before surgery and continued until euthanasia. Fresh feces were collected at 2 weeks before surgery, on the day of surgery, and 2, 4, 8 weeks postoperatively for 16S rRNA microbiome sequencing. Supraspinatus tendon-humerus ​(SSTH) complex was collected at 2, 4 and 8 weeks after surgery. Live parabacteroides distasonis (Parabacteroides distasonis) was used for repair of rotator cuff injury, with equal amount of pasteurized P. distasonis (KPD) or sterile anaerobic phosphate buffer saline (PBS) as control. Biomechanical, radiological, histological analysis were used to assess the effect of rotator cuff repair.ResultsBiomechanical, radiological and histological analysis indicated that intermittent fasting significantly promoted the repair of rotator cuff injury in the early postoperative period (P ＜ 0.05), but significantly inhibited the repair of rotator cuff injury at 4 weeks postoperatively (P ＜ 0.05). 16S rRNA Microbiome sequencing result showed that P. distasonis was the species with the most obvious changes in intestinal flora of mice after fasting. The results of tensile test, X-ray analysis and histological analysis indicated that the live P. distasonis (LPD) significantly impaired the biomechanical properties, bone regeneration and fibrocartilage regeneration of enthesis postoperatively (P ＜ 0.05).ConclusionIntermittent fasting promoted repair of rotator cuff injury in the early postoperative period by regulating the gut microbiota, in which P. distasonis played an important role.The translational potential of this articleIntermittent fasting (IF) may be a beneficial lifestyle for the repair of rotator cuff injury in the early postoperative period in clinical, and the influence of a certain strain on the repair of rotator cuff injury may also provide an idea for the treatment of rotator cuff injury in the future.

In Silico Study of Cell Surface Structures of Parabacteroides distasonis Involved in Its Maintenance within the Gut Microbiota.

The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and potential as a new biotherapeutic product. However, no study has yet investigated the cell surface molecules and structures of P. distasonis that allow its maintenance within the gut microbiota. Moreover, although P. distasonis is strongly recognized as an intestinal commensal species with benefits for its host, several works displayed controversial results, showing it as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-typing classification in order to better understand and characterize the beneficial/pathogenic behavior related to P. distasonis strains. Two different types of fimbriae, three different types of pilus and up to fourteen capsular polysaccharide loci were identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed of P. distasonis adhesion capacities and its potential pathogenicity, but no specific structure related to P. distasonis beneficial or detrimental activity was identified.

Roles of intestinal Parabacteroides in human health and diseases.

The stability of gut microbiota is essential for the host's health. Parabacteroides spp., core members of the human gut microbiota, have an average abundance of 1.27% in humans of 12 populations. Parabacteroides have recently been reported to have a close relationship with host health (e.g. metabolic syndrome, inflammatory bowel disease and obesity). Parabacteroides have the physiological characteristics of carbohydrate metabolism and secreting short chain fatty acids. However, antimicrobial resistance of Parabacteroides to antibiotics (such as clindamycin, moxifloxacin and cefoxitin) should not be ignored. In this review, we primarily focus on Parabacteroides distasonis, Parabacteroides goldsteinii, Parabacteroides johnsonii and Parabacteroides merdae and discuss their relationships with host disease, diet and the prevention or induction of diseases. Pa. distasonis and Pa. goldsteinii may be viewed as potential next generation probiotic candidates due to their protective effects on inflammation and obesity in mice. We also discuss the potential therapeutic application of Parabacteroides spp. in maintaining host-intestine homeostasis.

A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. One of the earliest aspects of this process is the development of autoantibodies and T cells directed at an epitope in the B-chain of insulin (insB:9-23). Analysis of microbial protein sequences with homology to the insB:9-23 sequence revealed 17 peptides showing >50% identity to insB:9-23. Of these 17 peptides, the hprt4-18 peptide, found in the normal human gut commensal Parabacteroides distasonis, activated both human T cell clones from T1D patients and T cell hybridomas from nonobese diabetic (NOD) mice specific to insB:9-23. Immunization of NOD mice with P. distasonis insB:9-23 peptide mimic or insB:9-23 peptide verified immune cross-reactivity. Colonization of female NOD mice with P. distasonis accelerated the development of T1D, increasing macrophages, dendritic cells, and destructive CD8+ T cells, while decreasing FoxP3+ regulatory T cells. Western blot analysis identified P. distasonis-reacting antibodies in sera of NOD mice colonized with P. distasonis and human T1D patients. Furthermore, adoptive transfer of splenocytes from P. distasonis-treated mice to NOD/SCID mice enhanced disease phenotype in the recipients. Finally, analysis of human children gut microbiome data from a longitudinal DIABIMMUNE study revealed that seroconversion rates (i.e., the proportion of individuals developing two or more autoantibodies) were consistently higher in children whose microbiome harbored sequences capable of producing the hprt4-18 peptide compared to individuals who did not harbor it. Taken together, these data demonstrate the potential role of a gut microbiota-derived insB:9-23-mimic peptide as a molecular trigger of T1D pathogenesis.

Similar bacterial signatures in the gut microbiota of type 1 and type 2 diabetes patients and its association with G protein-coupled receptor 41 and 43 gene expression.

There are conflicting reports regarding the abundance of short-chain fatty acids producing bacteria in the gut microbiota in patients with type 1 and type 2 diabetes. We aimed to determine the amount of Akkermansia muciniphila, Anaerobutyricum hallii, Bifidobacterium adolescentis, Bifidobacterium longum, Collinsella aerofaciens, Faecalibacterium prausnitzii, Lacticaseibacillus rhamnosus, and Parabacteroides distasonis in the gut microbiota in patients with type1 and type2 diabetes, compared with the healthy controls and analyze the correlation between the gene expression levels of two short-chain fatty acids receptors GPR41 and GPR43. Forty type 1, 40 type 2 stool and blood samples of diabetes patients, and 40 healthy control samples were studied. DNA and RNA were extracted, and bacteria were detected using a Microbial DNA qPCR Assay kit. Gene expressions were detected with GPR41 and GPR43 primers via in-house qPCR. Compared with healthy controls, B.longum and F.prausnitzii abundance were significantly decreased in patients with type1 and type2 diabetes, A.hallii abundance was increased in patients with type1 and decreased in type2 diabetes contrarily A.muciniphila abundance was decreased in patients with type1 and increased in type2 diabetes. GPR43 gene expression was upregulated in both patients group, however GPR41 was upregulated only in patients with type2 diabetes. Elevated B. longum and F. prausnitzii abundances were detected in the gut microbiota of patients with type1 and type2 diabetes and compared with healthy controls. B. longum and F.prausnitzii abundances were also correlated with the GPR43 gene expression level in type1 diabetes patients. Extensive studies determining bacteria producing short-chain fatty acids in gut microbiota, and their contribution in the pathogenesis of diabetes, are needed to understand better the mechanism of these diseases.

The Distinguishing Bacterial Features From Active and Remission Stages of Ulcerative Colitis Revealed by Paired Fecal Metagenomes.

Ulcerative colitis (UC) is a serious chronic intestinal inflammatory disease, with an increased incidence in recent years. The intestinal microbiota plays a key role in the pathogenesis of UC. However, there is no unified conclusion on how the intestinal microbiota changes. Most studies focus on the change between UC patients and healthy individuals, rather than the active and remission stage of the same patient. To minimize the influences of genetic differences, environmental and dietary factors, we studied the intestinal microbiota of paired fecal samples from 42 UC patients at the active and remission stages. We identified 175 species of microbes from 11 phyla and found no difference of the alpha and beta diversities between the active and remission stages. Paired t-test analysis revealed differential microbiota at levels of the phyla, class, order, family, genus, and species, including 13 species with differential abundance. For example, CAG-269 sp001916005, Eubacterium F sp003491505, Lachnospira sp000436475, et al. were downregulated in the remission, while the species of Parabacteroides distasonis, Prevotellamassilia sp900540885, CAG-495 sp001917125, et al. were upregulated in the remission. The 13 species can effectively distinguish the active and remission stages. Functional analysis showed that the sporulation and biosynthesis were downregulated, and the hydrogen peroxide catabolic process was upregulated in remission of UC. Our study suggests that the 13 species together may serve as a biomarker panel contributing to identify the active and remission stages of UC, which provides a valuable reference for the treatment of UC patients by FMT or other therapeutic methods.

Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression.

Simple SummaryAdvanced epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer due to the lack of available early screening methods that are available in clinical settings. Unique gastrointestinal (GI) microbiota have been detected in the ovaries and peritoneal fluid of women with EOC that are not found in women without disease. However, there are limited data available to determine possible links in GI microbiota composition and early ovarian cancer development while women are largely asymptomatic. This research utilizes an EOC animal model to investigate the effects of GI microbial disruption on systemic inflammation during early disease development and progression. The identification of distinct GI microbial communities that may potentially mediate systemic immune response during carcinogenesis can open new opportunities to disentangle the complex ovarian tumor microenvironment for the discovery of valid clinical tools for early EOC detection.GI microbiota has been implicated in producing the inflammatory tumor microenvironment of several cancers. Women with ovarian cancer often report GI-related symptoms at diagnosis although minimal is known about the possible GI bacteria that may trigger pro-tumorigenic immune responses in early EOC. The purpose of this study was to investigate the influences of GI microbiota dysbiosis on serum inflammatory markers during EOC utilizing a rodent model. This experimental design consisted of C57BL/6 mice randomly assigned to either the microbiota dysbiosis group (n = 6) or control group (n = 5). The CD7BL/6 mice assigned to the microbiota dysbiosis group were administered a mixture of broad-spectrum antibiotics (bacitracin and neomycin) for 2 weeks. Both groups were injected intraperitoneally with mouse ovarian epithelial cells that induce ovarian tumorigenesis. Levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were assessed in the serum, and the composition of the GI microbiota in fecal samples was measured using 16S rRNA gene sequencing. Overall CRP serum levels were significantly lower and TNFα levels were significantly higher in the microbiota dysbiosis group compared to the control group. The abundances of microbiota that correlated with CRP serum levels in the combined groups were genus Parabacteroides, Roseburia, and Emergencia and species Ruminococcus faecis, Parabacteroides distasonis, Roseburia Faecis, and Emergencia timonensis. This study provides evidence to support for further investigation of the GI microbial profiles in patients at risk of EOC.

Understanding the Dynamics of Gut Microbiota Composition and Function Following Short-Term Resistant Starch Supplementation

ObjectivesIncreased dietary fiber intake is recommended as a potential gut microbiota-targeted nutritional strategy to reduce the risk of metabolic diseases. However, individuals’ gut microbiome composition can change differently in response to specific dietary fibers. The objective of this study is to assess, through a resistant starch intervention, the factors that could be responsible for this heterogeneity in gut microbial alterations such as baseline gut microbiota and usual dietary fiber intake.MethodsHealthy adults (n = 75) were enrolled in a 7.5-week randomized crossover dietary intervention study consisting of three 10-day treatment periods during which they consumed resistant starch type 2 (RS2), resistant starch type 4 (RS4), or a control digestible starch, in the form of crackers. The three treatment periods were separated by 5-day washouts with no cracker consumption. We performed 16S rRNA gene sequencing on fecal samples to characterize the gut microbiota, and measured fecal short-chain fatty acids (SCFA) and bile acids. We used QIIME2 to identify amplicon sequence variants (ASVs) in the 16S rRNA sequence data, MaAsLin2 to evaluate the effect of predictor variables on differential abundances of microbes, and linear mixed models to analyze changes in fecal SCFA and bile acids.ResultsWe found significant changes in microbial composition after RS consumption but not after the control. Specifically, six ASVs were enriched including R. bromii and F. prausnitzii, which have been associated with butyrate production, after RS2 but not after RS4. Twelve ASVs increased after RS4, including Parabacteroides distasonis, which has been shown to be associated with protection against diseases like type 2 diabetes. There were no ASVs that significantly differed after the control. For all reported significant findings, q < 0.05.ConclusionsA short-term RS intervention resulted in RS type-specific gut microbial composition changes in healthy individuals. Ongoing analyses will further evaluate the predictors of gut microbiome changes in response to RS consumption by incorporating usual dietary intake, baseline gut microbiome composition, and host genetics.Funding SourcesNIH NIDDK T32 Award and the President's Council of Cornell Women.

Visceral Adiposity Is Associated With Shifts in the Gut Bacterial and Phage Microbiome in Postmenopausal Women

ObjectivesMore than 40% of U.S. adults are obese. Obesity, and in particular abdominal obesity, is associated with increased risk for developing a variety of chronic diseases. Obesity, aging, and menopause are each associated with differential shifts in the gut microbiome. We examined the association of visceral adiposity tissue (VAT) and the gut bacterial and phage microbiome.MethodsWe selected postmenopausal women (mean age 78 yrs) from the extremes of VAT (n = 25 per group; low VAT area (45.6 ± 12.5 cm2) and high VAT area (179.6 ± 30.4 cm2)) using data from dual x-ray absorptiometry (DXA) scans and performed shotgun metagenomic sequencing on fecal DNA collected at the time of DXA scan. Women with history of hypertension, diabetes, hormone therapy use, or antibiotic use within 90 days from sample collection were excluded. DNA libraries were prepared using the Illumina Nextera XT library preparation kit and libraries were sequenced on an Illumina HiSeq platform to generate 150-bp paired-ends reads. We examined the α-diversity (Shannon or Chao1), principal coordinate analysis β-diversity distances, and prevalence of microbiome taxa comparing the high vs. low VAT groups.ResultsThere was no significant difference in α-diversity or β-diversity between VAT groups. At the phyla level, women with high VAT displayed elevated Bacteroidetes and Proteobacteria proportional abundance (p < 0.05). At the species level, women with low VAT displayed significantly elevated proportional abundance of Alistipes shahii, Anaerostipes hadrus, and Blautia wexlerae. Women with high VAT area displayed significantly elevated Parabacteroides distasonis, Bacteroides uniformis, and Roseburia intestinalis. Women with high VAT displayed elevated proportional abundance of Escherichia phage TL-2011b (p < 0.05).ConclusionsData suggest that postmenopausal women with high VAT display a differential bacterial microbiome and phage profile compared to postmenopausal women with low VAT, consistent with changes seen with age. Moreover, we identified an elevated proportional abundance of Alistipes shahii, Anaerostipes hadrus, and Blautia wexlerae in women with low VAT, suggesting potential for anti-obesity activity of these microbes in postmenopausal women.Funding SourcesDOD BCRP Breakthrough Award to KLC. The WHI program is funded by the NHLBI/NIH. NIDCR/NIH R01 to JW-W.

A Prebiotic Diet Alters the Fecal Microbiome and Improves Sleep in Response to Sleep Disruption in Rats.

Sleep disruption is a challenging and exceedingly common physiological state that contributes to a wide range of biochemical and molecular perturbations and has been linked to numerous adverse health outcomes. Modern society exerts significant pressure on the sleep/wake cycle via myriad factors, including exposure to electric light, psychological stressors, technological interconnection, jet travel, shift work, and widespread use of sleep-affecting compounds. Interestingly, recent research has identified a link between the microbiome and the regulation of sleep, suggesting that interventions targeting the microbiome may offer unique therapeutic approaches to challenges posed by sleep disruption. In this study, we test the hypothesis that administration of a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) in adult male rats improves sleep in response to repeated sleep disruption and during recovery sleep. We found that animals fed the GOS/PDX prebiotic diet for 4 weeks exhibit increased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during 5 days of sleep disruption and increased total sleep time during 24 h of recovery from sleep disruption compared to animals fed a control diet, despite similar baseline sleep characteristics. Further, the GOS/PDX prebiotic diet led to significant changes in the fecal microbiome. Consistent with previous reports, the prebiotic diet increased the relative abundance of the species Parabacteroides distasonis, which positively correlated with sleep parameters during recovery sleep. Taken together, these findings suggest that the GOS/PDX prebiotic diet may offer an approach to improve resilience to the physiologic challenge of sleep disruption, in part through impacts on the microbiome.

Alterations in the Gut Microbiota of Tibetan Patients With Echinococcosis.

There are two main types of echinococcosis, namely alveolar echinococcosis (AE) and cystic echinococcosis (CE). They are zoonotic parasitic diseases caused by the metacestodes of Echinococcus multilocularis and Echinococcus granulosus. In order to explore the gut microbiome composition of patients with echinococcosis, we analyzed fecal samples of seven patients with AE, six patients with CE, and 13 healthy individuals from the Qinghai-Tibetan Plateau, China. Using metagenomic next-generation sequencing, we identified fecal bacteria in the patients with AE and CE. The gut microbiota was analyzed by next-generation metagenomic sequencing (mNGS) to compare patients with either AE or CE against healthy individuals. We found there were some differences between them in abundant bacteria. Our results led to five findings: (1) Between patients with echinococcosis and healthy individuals, the differential bacteria were from four phyla: Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria. (2) Rothia mucilaginosa, Veillonella dispar, Veillonella atypica, Streptococcus parasanguinis, Streptococcus salivarius, and Alistipes finegoldii were abundant in the feces of patients with AE. (3) Bacteroides dorei, Parabacteroides distasonis, Escherichia sp_E4742, and Methanobrevibacter smithii were abundant in the feces of the patients with CE. (4) At the phylum and class level, compared to the AE group, the healthy group was characterized by higher numbers of Actinobacteria. (5) At the family level, Lachnospiraceae and Eubacteriaceae were more abundant in the feces of healthy individuals than in AE patients. The genera Coprococcus, Eubacterium, and Bilophia were more abundant in the healthy group, while the genus Rothia was more abundant in the AE group. The results of this study enrich our understanding of the gut microbiome composition of patients with AE and CE in the Qinghai-Tibetan Plateau.

Structural analysis and immunomodulatory activity of a homopolysaccharide isolated from Parabacteroides distasonis

A homopolysaccharide fraction (PEP-1A) with desired immunomodulatory activity was isolated from culture broth of Parabacteroides distasonis . Structural characterization uncovered that PEP-1A had a molecular weight of 3.40 × 10 6 Da and possessed mannose merely. Comprehensive analysis of FT-IR, GC–MS and 1D/2D NMR confirmed that the structure of PEP-1A was expected as follows: Finally, the activity assays on RAW 264.7 macrophages showed that PEP-1A could promote proliferation, increase the production of reactive oxygen species (ROS), enhance the phagocytosis, and promote the secretion of nitric oxide (NO) and inflammatory cytokines including IL-1β, IL-6 and TNF-α. Furthermore, PEP-1A could give play to immunoregulation effect through NF-κB, MAPK and Akt signaling pathways. Collectively, the study of PEP-1A offers a molecular underpinning for the future application of PEP-1A as a potential immunostimulant.

Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice

Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut microbiome associated with energy harvest alters dramatically in response to nutrient deprivation. Here, we reported that CR and high-fat diet (HFD) both remodeled the gut microbiota with similar microbial composition, Parabacteroides distasonis was most significantly decreased after CR or HFD. CR altered microbiota and reprogramed metabolism, resulting in a distinct serum bile acid profile characterized by depleting the proportion of non-12α-hydroxylated bile acids, ursodeoxycholic acid and lithocholic acid. Downregulation of UCP1 expression in brown adipose tissue and decreased serum GLP-1 were observed in the weight-rebound mice. Moreover, treatment with Parabacteroides distasonis or non-12α-hydroxylated bile acids ameliorated weight regain via increased thermogenesis. Our results highlighted the gut microbiota-bile acid crosstalk in rebound weight gain and Parabacteroides distasonis as a potential probiotic to prevent rapid post-CR weight gain.

Gut Microbiota Dysbiosis and Altered Bile Acid Catabolism Lead to Metabolic Disorder in Psoriasis Mice.

Patients with psoriasis tend to have significant comorbidities, such as hyperlipemia, diabetes mellitus, and obesity, which belong to metabolic disorders. The specific mechanism through which psoriasis increases the metabolic disorder risk is uncertain. In this study, we demonstrated that the dysbiotic gut microbiota of 6-month-old psoriasis-like model mice (K14-VEGF-A-transgenic) exacerbated psoriasis disease and induced metabolic disorder when transferred into 2-month-old mice. By 16S rRNA gene sequencing, we confirmed that the Parabacteroides distasonis decreased with age in K14-VEGF mice, and P. distasonis also decreased in the transferred mice. Metabolomic screening identified an altered bile acid profile, including a decrease in chenodeoxycholic acid (CDCA) in the feces of transferred mice. Additionally, CDCA supplements prevented metabolic disorders in K14-VEGF-A-transgenic mice. Consequently, we found that aberrant bile acid metabolism may contribute to metabolic disorder in K14-VEGF-A-transgenic mice, indicating the possibility to prevent and treat the metabolic disorder in psoriasis mice by targeting gut microbial metabolites.

Cigarette smoke promotes colorectal cancer through modulation of gut microbiota and related metabolites

ObjectiveCigarette smoking is a major risk factor for colorectal cancer (CRC). We aimed to investigate whether cigarette smoke promotes CRC by altering the gut microbiota and related metabolites.DesignAzoxymethane-treated C57BL/6 mice...

Diet Supplementation with NUTRIOSE, a Resistant Dextrin, Increases the Abundance of Parabacteroides distasonis in the Human Gut.

ScopeAn imbalance of the gut microbiota (“dysbiosis”) is associated with numerous chronic diseases, and its modulation is a promising novel therapeutic approach. Dietary supplementation with soluble fiber is one of several proposed modulation strategies. This study aims at confirming the impact of the resistant dextrin NUTRIOSE (RD), a soluble fiber with demonstrated beneficial health effects, on the gut microbiota of healthy individuals.Methods and resultsFifty healthy women are enrolled and supplemented daily with either RD (n = 24) or a control product (n = 26) during 6 weeks. Characterization of the fecal metagenome with shotgun sequencing reveals that RD intake dramatically increases the abundance of the commensal bacterium Parabacteroides distasonis. Furthermore, presence in metagenomes of accessory genes from P. distasonis, coding for susCD (a starch‐binding membrane protein complex) is associated with a greater increase of the species. This suggests that response to RD might be strain‐dependent.ConclusionSupplementation with RD can be used to specifically increase P. distasonis in gut microbiota of healthy women. The magnitude of the response may be associated with fiber‐metabolizing capabilities of strains carried by subjects. Further research will seek to confirm that P. distasonis directly modulates the clinical effects observed in other studies.

The microbiota-gut-kidney axis mediates host osmoregulation in a small desert mammal

Regulating sodium and water balances is crucial for survival of small, desert mammals. Studies demonstrate that the gut microbiota and their metabolites are involved in host energy homeostasis, but little is known on the interactions among salt loading, gut microbiota, and osmoregulation. The aim of this study was to fill this gap. Mongolian gerbils (Meriones unguiculatus) were offered drinking water (Con) and either water containing moderate (4%, MS) or high NaCl (8%, HS) ad libitum. Intake of HS reduced α diversity of the microbial community and, at the genus level, reduced the relative abundances of Rikenella and Christensenella but increased Atopobium. To confirm the function of gut microbiota in host osmoregulation, we transplanted caecal microbiota in HS gerbils. To cope with salt loading, the gerbils concentrated urine, resulting in negative energy balance and systemic inflammation. The HS gerbils increased hypothalamic arginine vasopressin and intestinal and renal aquaporin 2 to support water retention, and reduced intestinal and renal epithelial sodium channel α to promote sodium excretion. However, HS gerbils with caecal microbiota transplant (CMT) from Con donors maintained energy balance and osmoregulation, and had a much reduced systemic inflammation. Further, CMT from Con donors to HS recipients reshaped the gut microbiota, particularly by reducing Parabacteroides distasonis and Prevotella copri, and increasing Lactobacillus reuteri abundances, with a resulting increase in bacterial metabolites such as butyrate. These findings highlight a vital role of the microbiota-gut-kidney axis in mediating salt-related osmoregulation, allowing small mammals to adapt to high salt loads in a desert habitat.

Gut Microbiota Feature of Senile Osteoporosis by Shallow Shotgun Sequencing Using Aged Rats Model.

Senile osteoporosis is defined as an age-related bone metabolic disorder, which is characterized by bone loss and decreased bone fragility. Gut microbiota (GM) could regulate the bone metabolic process and be closely related to senile osteoporosis. Several genus-level GM were found to increase in osteoporotic animals and patients. However, to reveal the pathogenic bacteria in senile osteoporosis, further studies are still needed to investigate the complete characteristics of bacteria species. In the present study, the rats were equally divided into two groups: the control group (Con, 6-month-old) and the osteoporosis group (OP, 22-month-old). Fecal samples were freshly collected to conduct the shallow shotgun sequencing. Then, we compared the species numbers, microbial diversity, GM composition at genus and species-level, and functional metabolic pathways in the two groups. The results showed that the species number was lower in the OP group (1272) than in the control group (1413), and 1002 GM species were shared between the two groups. The OP group had the decreased α diversity compared with the control group. As for β diversity, The PCA revealed that samples in the two groups had distinguishable ecological distance in each coordinate. At the species level, Bacteroide coprocola (B. coprocola), Acinetobacter baumannii (A. baumannii), Parabacteroides distasonis (P. distasonis), and Prevotella copri (P. copri) were higher in the OP group, while Corynebacterium stationis (C. stationis), Akkermansia muciniphila (A. muciniphila), and Alistipes indistinctus (A. indistinctus) were decreased. Moreover, functional metabolic analysis revealed that metabolic pathways of fatty acid biosynthesis, valine/isoleucine biosynthesis, GABA biosynthesis, and ubiquinone biosynthesis were enriched in the senile osteoporotic rats. In conclusion, GM at the species level in senile osteoporotic rats was significantly altered in structure, composition, and function. The altered GM structure, increased GM species such as P. copri, and decreased GM species such as A. muciniphila might be linked with the development of senile osteoporosis.

Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver by Remodeling the Liver Immune Microenvironment

Background/AimsThis study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis.MethodsA series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis.ResultsFewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniformis were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B. vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration.ConclusionsAn increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Increasing the diversity of dietary fibers in a daily-consumed bread modifies gut microbiota and metabolic profile in subjects at cardiometabolic risk

ABSTRACT Some cardiometabolic risk factors such as dyslipidemia and insulin resistance are known to be associated with low gut microbiota richness. A link between gut microbiota richness and the diversity of consumed dietary fibers (DF) has also been reported. We introduced a larger diversity of consumed DF by using a daily consumed bread in subjects at cardiometabolic risk and assessed the impacts on the composition and functions of gut microbiota as well as on cardiometabolic profile. Thirty-nine subjects at cardiometabolic risk were included in a double-blind, randomized, cross-over, twice 8-week study, and consumed daily 150 g of standard bread or enriched with a 7-dietary fiber mixture (5.55 g and 16.05 g of fibers, respectively). Before and after intervention, stool samples were collected for gut microbiota analysis from species determination down to gene-level abundance using shotgun metagenomics, and cardiometabolic profile was assessed. Multi-fiber bread consumption significantly decreased Bacteroides vulgatus, whereas it increased Parabacteroides distasonis, Fusicatenibacter saccharivorans, an unclassified Acutalibacteraceae and an unclassified Eisenbergiella (q < 0.1). The fraction of gut microbiota carrying the gene coding for five families/subfamilies of glycoside hydrolases (CAZymes) were also increased and negatively correlated with peaks and total/incremental area under curve (tAUC/iAUC) of postprandial glycemia and insulinemia. Compared to control bread, multi-fiber bread decreased total cholesterol (−0.42 mM; q < 0.01), LDL cholesterol (−0.36 mM; q < 0.01), insulin (−2.77 mIU/l; q < 0.05), and HOMA (−0.78; q < 0.05). In conclusion, increasing the diversity of DF in a daily consumed product modifies gut microbiota composition and function and could be a relevant nutritional tool to improve cardiometabolic profile.