Associations between dietary habits, socio-demographics and gut microbial composition in adolescents.

The relationship between dietary habits and microbiota composition during adolescence has not been well examined. This is a crucial knowledge gap to fill considering that diet-microbiota interactions influence neurodevelopment, immune system maturation and metabolic regulation. This study examined the associations between diet and the gut microbiota in a school-based sample of 136 adolescents (Mage = 12·1 years; age range 11-13 years; 48 % female; 47 % Black, 38 % non-Hispanic White, 15 % Hispanic or other minorities) from urban, suburban and rural areas in the Southeast USA. Adolescents completed the Rapid Eating Assessment for Participants and provided stool samples for 16S ribosomal RNA gene sequencing. Parents reported their child and family socio-demographic characteristics. The associations between diet and socio-demographics with gut microbiota diversity and abundance were analysed using multivariable regression models. Child race and ethnicity, sex, socio-economic status and geographic locale contributed to variation within microbiota composition (ß-diversity). Greater consumption of processed meat was associated with a lower microbial α-diversity after adjusting for socio-demographic variables. Multi-adjusted models showed that frequent consumption of nutrient-poor, energy-dense foods (e.g. sugar-sweetened beverages, fried foods, sweets) was negatively associated with abundances of genera in the family Lachnospiraceae (Anaerostipes, Fusicatenibacter and Roseburia), which are thought to play a beneficial role in host health through their production of short-chain fatty acids (SCFAs). These results provide new insights into the complex relationships among socio-demographic factors, diet and gut microbiota during adolescence. Adolescence may represent a critical window of opportunity to promote healthy eating practices that shape a homoeostatic gut microbiota with life-long benefits.

Mood disturbance, but not overall diet quality, is associated with fecal microbiome diversity in free-living adults.

OBJECTIVES: To investigate the gut-brain axis, we explored the relationships among mood disturbance (MD), diet quality (DQ), and fecal microbiota in free-living adults. METHODS: A cross-sectional analysis was conducted with data from 75 healthy adults enrolled in two studies. Anthropometrics, 16s rRNA gene sequencing of fecal microbes, DQ as assessed by Healthy Eating Index-2015 (HEI), and MD determined by Profile of Mood States (POMS) were included. Alpha-diversity and DQ differences were explored between low (n = 37) and high MD (n = 38) groups. Spearman correlations were used to investigate relationships between alpha-diversity, DQ, and POMS subscales. Moderation analysis explored the effect of HEI score on the relationship between MD and alpha-diversity. RESULTS: Participants were mostly white (67%), 54.5 years old (±11.8), and overweight (28.5 ± 6.5 kg/m2). Shannon and Simpson indices indicate higher alpha-diversity in participants with low MD compared to high MD (p = 0.004 and p = 0.008, respectively). Simpson and Shannon indices were correlated with subscale of anger (rho = -0.303, p = 0.011; rho = -0.265, p = 0.027, respectively)and total MD (rho = -0.404, p = 0.001; rho = -0.357, p = 0.002, respectively). Refined grains were associated with fatigue and tension subscales (rho = 0.428, p < 0.001; rho = 0.302, p = 0.014, respectively). DQ did not significantly moderate the relationship between alpha-diversity and mood disturbance (F(7, 53) = 2.00, p = 0.072, R2 = 0.209). Shannon index was a significant predictor of MD (b = -4.39, t(53) = -2.55, p = 0.014), but total HEI score and the interaction (Shannon index*HEI score) were not significant. DISCUSSION: Greater bacterial diversity was associated with lower MD, and DQ was associated with various mood state subscales in this sample of adults.

ICOS ligand and IL-10 synergize to promote host-microbiota mutualism.

Genome-wide association studies have identified ICOSLG, which encodes the inducible costimulator ligand (ICOSLG or ICOSL) as a susceptibility locus for inflammatory bowel disease. ICOSL has been implicated in the enhancement of pattern recognition receptor signaling in dendritic cells, induction of IL-10 production by CD4 T cells, and the generation of high-affinity antibodies to specific antigens-all of which can potentially explain its involvement in gastrointestinal inflammation. Here, we show that murine ICOSL deficiency results in significant enrichment of IL-10-producing CD4 T cells particularly in the proximal large intestine. Transient depletion of IL-10-producing cells from adult ICOSL-deficient mice induced severe colonic inflammation that was prevented when mice were first treated with metronidazole. ICOSL-deficient mice displayed reduced IgA and IgG antibodies in the colon mucus and impaired serum antibody recognition of microbial antigens, including flagellins derived from mucus-associated bacteria of the Lachnospiraceae family. Confirming the synergy between ICOSL and IL-10, ICOSL deficiency coupled with CD4-specific deletion of the Il10 gene resulted in juvenile onset colitis that was impeded when pups were fostered by ICOSL-sufficient dams. In this setting, we found that both maternally acquired and host-derived antibodies contribute to the life anti-commensal antibody repertoire that mediates this protection in early life. Collectively, our findings reveal a partnership between ICOSL-dependent anti-commensal antibodies and IL-10 in adaptive immune regulation of the microbiota in the large intestine. Furthermore, we identify ICOSL deficiency as an effective platform for exploring the functions of anti-commensal antibodies in host-microbiota mutualism.

Gastrointestinal symptoms, diagnostic evaluations, and abdominal pathology in children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) frequently present with acute pain. The abdomen, a common site of acute SCD-related pain, may be present in a variety of gastrointestinal (GI) pathologies. Limited data exist on prevalence and workup of abdominal pain in patients with SCD during acute pain events. OBJECTIVES: Determine prevalence of GI symptoms, GI-specific evaluation and risks of hospitalization in children with SCD presenting to the emergency department (ED) or hospitalized with abdominal pain. METHODS: Retrospective study of children less than 21 years presenting to the ED or hospitalized with pain in our center over 2 years. Descriptive statistics were used to report clinical characteristics, frequency of GI symptoms, workup by age (<5 vs. ≥5 years), and genotype (sickle cell anemia [SCA] vs. non-SCA). Logistic regression models were used to identify risks associated with hospitalization. RESULTS: A total of 1279 encounters in 378 patients were analyzed; 23% (n = 291) encounters were associated with abdominal pain. More abdominal pain-associated hospitalizations occurred in older children, SCA, children with lower mean hemoglobin (8.7 ± 1.9 vs. 9.6 ± 1.6 g/dL, p < .001) and higher mean white blood cell (WBC) count (14.9 ± 6.6 vs. 13.2 ± 5.3 × 103 /µL, p = .02). We identified that less than 50% of patients presenting to the ED with abdominal pain received a GI-specific evaluation. CONCLUSION: Children with SCD frequently present with abdominal pain and other GI symptoms, with limited GI evaluations performed. GI-specific evaluation may increase diagnosis of GI pathologies, rule out GI pathologies, and contribute to the limited knowledge of the abdomen as a primary site of SCD pain.

The faecal microbiota is distinct in HLA-B27+ ankylosing spondylitis patients versus HLA-B27+ healthy controls.

OBJECTIVES: Spondyloarthritis (SpA) results from the interplay between genetic and environmental factors. An emerging modifiable factor is the human intestinal microbiota, which multiple studies in children and adults have shown to be abnormal in SpA patients, including enthesitis related arthritis and ankylosing spondylitis (AS). However, HLA-B27 itself appears to impact the contents of the microbiota and is more common in SpA patients versus controls, thus serving as a confounding factor in most comparative studies. METHODS: This was a cross-sectional study that evaluated the contents of the faecal microbiota among 29 patients with HLA-B27+ AS and 43 healthy adults who underwent 16S sequencing and genotyping as part of the TwinsUK Programme. RESULTS: HLA-B27 positive+ patients and healthy controls demonstrated substantial clustering based upon diagnosis. Decreased richness was observed among the AS patients, although measures of evenness were similar. After correction for multiple comparisons, several taxa - including Faecalibacterium prausnitzii and Coprococcus - were elevated in AS patients compared to controls, even when restricted to female subjects, while Bacteroides fragilis, Ruminococcus, and Akkermansia muciniphila were depleted in AS patients. CONCLUSIONS: Consistent with some previous studies, our study demonstrates in patients with AS associations with Coprococcus, Bacteroides, and Ruminococcus. Other findings, including increased Faecalibacterium, are inconsistent with previous studies and thus potentially underscore the necessity of evaluating HLA-B27 positive controls in studies evaluating the impact of the intestinal microbiota on SpA.

Dietary Supplementation of Inulin Contributes to the Prevention of Estrogen Receptor-Negative Mammary Cancer by Alteration of Gut Microbial Communities and Epigenetic Regulations.

Breast cancer (BC) is among the most frequently diagnosed malignant cancers in women in the United States. Diet and nutrition supplementation are closely related to BC onset and progression, and inulin is commercially available as a health supplement to improve gut health. However, little is known with respect to inulin intake for BC prevention. We investigated the effect of an inulin-supplemented diet on the prevention of estrogen receptor-negative mammary carcinoma in a transgenic mouse model. Plasma short-chain fatty acids were measured, the gut microbial composition was analyzed, and the expression of proteins related to cell cycle and epigenetics-related genes was measured. Inulin supplementation greatly inhibited tumor growth and significantly delayed tumor latency. The mice that consumed inulin had a distinct microbiome and higher diversity of gut microbial composition compared to the control. The concentration of propionic acid in plasma was significantly higher in the inulin-supplemented group. The protein expression of epigenetic-modulating histone deacetylase 2 (Hdac2), Hdac8, and DNA methyltransferase 3b decreased. The protein expression of factors related to tumor cell proliferation and survival, such as Akt, phospho-PI3K, and NF-kB, also decreased with inulin administration. Furthermore, sodium propionate showed BC prevention effect in vivo through epigenetic regulations. These studies suggest that modulating microbial composition through inulin consumption may be a promising strategy for BC prevention.

Health-related quality of life is associated with fecal microbial composition in breast cancer survivors.

PURPOSE: To investigate relationships between body size, gut microbiome, and health-related quality of life (QOL) in breast cancer survivors (BCS) in a clinical trial. METHODS: A cross-sectional substudy was conducted using baseline data from 70 BCS participating in a randomized controlled trial of a lifestyle intervention. Measures included anthropometrics, QOL (Short Form Health-related QOL Survey-36 [SF-36]), and 16S rRNA gene sequencing of fecal microbes. Participants were categorized by body mass index (BMI) into without obesity (≤ 29.9 kg/m2; n = 38) and with obesity (≥ 30.0 kg/m2; n = 32) groups. Differences in bacterial taxa between groups were assessed using Kruskal-Wallis one-way analysis of variance. Spearman and partial correlations explored associations between taxa and SF-36 subscales. Mediation analysis explored the relationship between BMI and SF-36 mental health summary score with alpha diversity as a mediator. RESULTS: Most BCS (72.9%) were non-Hispanic White with average age of 61.6 (± 8.7) years. No differences were observed for SF-36 subscales between groups. Physical functioning, vitality, and mental health subscales were negatively associated with Ruminococcus (ρ = - 0.304, p = 0.036; ρ = - 0.361, p = 0.012; ρ = - 0.495, p < 0.001) and Dorea (ρ = - 0.378, p = 0.028; ρ = - 0.33, p = 0.022; ρ = - 0.388, p = 0.006) abundance controlling for BMI. BCS without obesity had a significantly higher relative abundance of Ruminococcus (p = 0.003), Streptococcus (p = 0.049), Roseburia (p = 0.035), and Dorea (p = 0.003). CONCLUSIONS: Fecal microbial composition differed between BCS with and without obesity, with associations between QOL and several microbial taxa. Several of these genera, previously identified as potentially beneficial, may also influence QOL in BCS. These results support further studies to determine the role of individual microbiota in QOL and obesity in cancer survivors.

Microbial Composition and Genes for Key Metabolic Attributes in the Gut Digesta of Sea Urchins Lytechinus variegatus and Strongylocentrotus purpuratus Using Shotgun Metagenomics.

This paper describes the microbial community composition and genes for key metabolic genes, particularly the nitrogen fixation of the mucous-enveloped gut digesta of green (Lytechinus variegatus) and purple (Strongylocentrotus purpuratus) sea urchins by using the shotgun metagenomics approach. Both green and purple urchins showed high relative abundances of Gammaproteobacteria at 30% and 60%, respectively. However, Alphaproteobacteria in the green urchins had higher relative abundances (20%) than the purple urchins (2%). At the genus level, Vibrio was dominant in both green (~9%) and purple (~10%) urchins, whereas Psychromonas was prevalent only in purple urchins (~24%). An enrichment of Roseobacter and Ruegeria was found in the green urchins, whereas purple urchins revealed a higher abundance of Shewanella, Photobacterium, and Bacteroides (q-value < 0.01). Analysis of key metabolic genes at the KEGG-Level-2 categories revealed genes for amino acids (~20%), nucleotides (~5%), cofactors and vitamins (~6%), energy (~5%), carbohydrates (~13%) metabolisms, and an abundance of genes for assimilatory nitrogen reduction pathway in both urchins. Overall, the results from this study revealed the differences in the microbial community and genes designated for the metabolic processes in the nutrient-rich sea urchin gut digesta, suggesting their likely importance to the host and their environment.

Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy.

BACKGROUND: To understand inter-individual variability of fecal microbe transplantation (FMT) to enhance anti-PD-1 immunotherapy (IT) for melanoma, we analyzed the data sets from two recent publications with a microbial strain-tracking tool to determine if donor strains were dominant in the recipient feces following FMT. RESULTS: Analysis of the Baruch et al. data set found that the presence of commensal donor microbes in recipient feces post-FMT did not correlate with the patient response to IT. From the Davar et al., data set, we found 4 patients that responded to IT had donor's related strain post-FMT, while 2 patients that did not respond to the IT also had donor's strain post-FMT. Importantly, we identified no donor microbes in the feces in one recipient post-FMT that responded to IT. Furthermore, in depth analysis from two patients who responded to IT revealed both donor and recipient strains at different times post-FMT. Colonization of the gastrointestinal tract niches is important for the interaction with the host immune system. Using a separate data set, we show that mucosa from the cecum, transverse colon, and sigmoid colon share strains, providing a large reservoir of niches containing recipient microbes. CONCLUSIONS: We demonstrated using strain-tracking analysis individual variation with the respect to the presence of fecal dominant donor microbes in the recipient following FMT that did not correlate with the response to anti-PD-1 immunotherapy. The inter-individual differences of FMT to enhance IT might be explained by the variability of the donor microbes to occupy and outcompete recipient microbes for the gastrointestinal niches. The result from our study supports the use of new approaches to clear the niches in the gastrointestinal tract to promote donor colonization to reduce inter-individual variability of IT for melanoma and potentially other cancers.

Changes in the gut microbiome community of nonhuman primates following radiation injury.

BACKGROUND: Composition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive weapon, on the composition of the gut microbiome. Therefore, we sought to analyze alterations to the gut microbiome of nonhuman primates (NHPs) exposed to high doses of radiation. Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) 1 day prior and 1 and 4 days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD70-80/60). The 16S V4 rRNA sequences were extracted from each sample, followed by bioinformatics analysis using the QIIME platform. RESULTS: Alpha Diversity (Shannon Diversity Index), revealed no major difference between pre- and post-irradiation, whereas Beta diversity analysis showed significant differences in the microbiome after irradiation (day + 4) compared to baseline (pre-irradiation). The Firmicutes/Bacteriodetes ratio, a factor known to be associated with disruption of metabolic homeostasis, decreased from 1.2 to less than 1 post-radiation exposure. Actinobacillus, Bacteroides, Prevotella (Paraprevotellaceae family) and Veillonella genera were significantly increased by more than 2-fold and Acinetobacter and Aerococcus genus were decreased by more than 10-fold post-irradiation. Fifty-two percent (10/19) of animals exposed to radiation demonstrated diarrhea at day 4 post-irradiation. Comparison of microbiome composition of feces from animals with and without diarrhea at day 4 post-irradiation revealed an increase in Lactobacillus reuteri associated with diarrhea and a decrease of Lentisphaerae and Verrucomicrobioa phyla and Bacteroides in animals exhibiting diarrhea. Animals with diarrhea at day 4 post-irradiation, had significantly lower levels of Lentisphaere and Verrucomicrobia phyla and Bacteroides genus at baseline before irradiation, suggesting a potential association between the prevalence of microbiomes and differential susceptibility to radiation-induced diarrhea. CONCLUSIONS: Our findings demonstrate that substantial alterations in the microbiome composition of NHPs occur following radiation injury and provide insight into early changes with high-dose, whole-body radiation exposure. Future studies will help identify microbiome biomarkers of radiation exposure and develop effective therapeutic intervention to mitigate the radiation injury.

Associations between Dietary Fiber, the Fecal Microbiota and Estrogen Metabolism in Postmenopausal Women with Breast Cancer.

Breast cancer is a hormonally-driven cancer, and various dietary factors are associated with estrogen metabolism, including dietary fiber. Several studies report associations between dietary fiber and breast cancer; however, research on whether fiber influences circulating estrogens through the gut microbiota is rare. The objective of this cross-sectional study among 29 newly-diagnosed (stage 0-II), post-menopausal breast cancer patients is to examine associations between dietary fiber and the gut microbiota that are linked with ß-glucuronidase activity, and purportedly increase circulating estrogens. Spearman's and partial correlations controlling for body mass index and age were performed using dietary recall data, Illumina MiSeq generated microbiota relative abundance, and HPLC-mass spectrometry-derived estradiol and estrone levels.Major findings are: (1) total dietary fiber is inversely associated with Clostridium hathewayi (r= -0.419; p = 0.024); (2) soluble fiber is inversely associated with Clostridium (r=-0.11; p = 0.02); (3) insoluble fiber is positively associated with Bacteroides uniformis sp. (r = 0.382; p = 0.041); and (4) serum estradiol and estrone levels are not correlated with species/genera or dietary fiber, though there is a trend toward an inverse association between soluble fiber and estradiol levels (r= -0.30; p = 0.12). More studies are needed to understand the complex interaction between dietary fiber, intestinal microbiota, and hormonal levels in older females.

In Silico and Experimental Evaluation of Primer Sets for Species-Level Resolution of the Vaginal Microbiota Using 16S Ribosomal RNA Gene Sequencing.

Background: Identification of bacteria in human vaginal specimens is commonly performed using 16S ribosomal RNA (rRNA) gene sequences. However, studies utilize different 16S primer sets, sequence databases, and parameters for sample and database clustering. Our goal was to assess the ability of these methods to detect common species of vaginal bacteria. Methods: We performed an in silico analysis of 16S rRNA gene primer sets, targeting different hypervariable regions. Using vaginal samples from women with bacterial vaginosis, we sequenced 16S genes using the V1-V3, V3-V4, and V4 primer sets. For analysis, we used an extended Greengenes database including 16S gene sequences from vaginal bacteria not already present. We compared results with those obtained using the SILVA 16S database. Using multiple database and sample clustering parameters, each primer set's ability to detect common vaginal bacteria at the species level was determined. We also compared these methods to the use of DADA2 for denoising and clustering of sequence reads. Results: V4 sequence reads clustered at 99% identity and using the 99% clustered, extended Greengenes database provided optimal species-level identification of vaginal bacteria. Conclusions: This study is a first step toward standardizing methods for 16S rRNA gene sequencing and bioinformatics analysis of vaginal microbiome data.

Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis.

Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler's Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5 vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.

Ultraviolet radiation, both UVA and UVB, influences the composition of the skin microbiome.

BACKGROUND: Studies have begun to investigate the complex relationship between host and microorganisms in non-infectious pathologies such as acne, atopic dermatitis and psoriasis. Though the skin is exposed to environmental stressors such as ultraviolet radiation (UVR), no studies exist examining the effects of both UVA and UVB on the skin microbiome. OBJECTIVE: To test the effect of UVA and UVB on human skin microbiome. METHODS: To test whether UV will alter the cutaneous microbiome, participants were exposed to doses of UVA (22-47 J/cm2 ) or UVB (100-350 mJ/cm2 ) and samples were collected. DNA was isolated and sequenced to identify the microbial composition of each sample. RESULTS: There was vast intra- and inter-subject variation at all time points, and phylum and species-level differences were identified. These included an increase in the phylum Cyanobacteria and a decrease in the family Lactobacillaceae and Pseudomonadaceae. The sensitivity of microbes to UVR and their re-colonization potential following exposure differed in UVA vs UVB samples. LIMITATIONS: The sample size was small, and the study was limited to males. CONCLUSION: The results demonstrate that UVR has profound qualitative and quantitative influences on the composition of the skin microbiome, possibly effecting skin pathology in which UVR is a factor.

Gut microbiota diversity is associated with cardiorespiratory fitness in post-primary treatment breast cancer survivors.

NEW FINDINGS: What is the central question of this study? Does the link between cardiorespiratory fitness and gut microbiota diversity persist after adjusting for the potential effects of percentage body fat and activity-related energy expenditure (AEE)? What is the main finding and its importance? This is the first study to examine the link between cardiorespiratory fitness and gut microbiota diversity while accounting for the underlying effects of percentage body fat and free-living AEE. Results from the present work suggest that cardiorespiratory fitness, not physical activity, is a superior correlate of gut microbiota diversity among post-primary treatment, non-metastatic breast cancer survivors. ABSTRACT: Cancer treatment uniquely triggers multiple physiological shifts detrimental to overall health. Although previous research indicates a link between the gut microbiota and cardiorespiratory fitness, it is unclear whether these findings are attributable to potential underlying effects of percentage body fat or free-living activity energy expenditure (AEE). The microbe composition of faecal specimens from 37 breast cancer survivors was determined using 16S microbiome analyses. Individual-sample microbiota diversity (α-diversity) and between-sample community differences (ß-diversity) were examined. Peak oxygen uptake ( V̇O2peak ) was estimated from a graded exercise test consistent with the modified Naughton protocol, in which exercise terminates at 85% of age-predicted maximal heart rate. The AEE was measured over 10 days using doubly labelled water, wherein the percentage body fat was calculated from total body water. Pearson correlations revealed α-diversity indices (Chao1, observed species, PD whole tree and Shannon) to be positively associated with V̇O2peak (r = 0.34-0.51; P < 0.05), whereas the percentage of maximal heart rate during stages 1-4 of the graded exercise test (r = -0.34 to -0.50; P < 0.05) and percentage body fat (r = -0.32 to -0.41; P < 0.05) were negatively associated with the same α-diversity indices. Multiple linear regression models showed that V̇O2peak accounted for 22 and 26% of the variance in taxonomic richness (observed species) and phylogenic diversity after adjustment for percentage body fat and menopausal status. Unweighted UniFrac (ß-diversity) was significant for several outcomes involving cardiorespiratory fitness, and significant taxa comparisons were found. Associations between gut microbiota and free-living AEE were not found. Results from the present work suggest that cardiorespiratory fitness, not physical activity, is a superior correlate of gut microbiota diversity.

Ocean warming alters predicted microbiome functionality in a common sea urchin.

The microbiome of sea urchins plays a role in maintaining digestive health and innate immunity. Here, we investigated the effects of long-term (90 day) exposure to elevated seawater temperatures on the microbiome of the common, subtropical sea urchin Lytechinus variegatus The community composition and diversity of microbes varied according to the type of sample collected from the sea urchin (seawater, feed, intestines, coelomic fluid, digested pellet and faeces), with the lowest microbial diversity (predominately the order Campylobacterales) located in the intestinal tissue. Sea urchins exposed to near-future seawater temperatures maintained the community structure and diversity of microbes associated with their tissues. However, marginal, non-significant shifts in microbial community structure with elevated temperature resulted in significant changes in predicted metagenomic functions such as membrane transport and amino acid and carbohydrate metabolism. The predicted changes in key metabolic categories suggest that near-future climate-induced increases in seawater temperature could shift microbial community function and impact sea urchin digestive and immune physiology.

Gut Microbial Dysbiosis Due to Helicobacter Drives an Increase in Marginal Zone B Cells in the Absence of IL-10 Signaling in Macrophages.

It is clear that IL-10 plays an essential role in maintaining homeostasis in the gut in response to the microbiome. However, it is unknown whether IL-10 also facilitates immune homeostasis at distal sites. To address this question, we asked whether splenic immune populations were altered in IL-10-deficient (Il10(-/-)) mice in which differences in animal husbandry history were associated with susceptibility to spontaneous enterocolitis that is microbiome dependent. The susceptible mice exhibited a significant increase in splenic macrophages, neutrophils, and marginal zone (MZ) B cells that was inhibited by IL-10 signaling in myeloid, but not B cells. The increase in macrophages was due to increased proliferation that correlated with a subsequent enhancement in MZ B cell differentiation. Cohousing and antibiotic treatment studies suggested that the alteration in immune homeostasis in the spleen was microbiome dependent. The 16S rRNA sequencing revealed that susceptible mice harbored a different microbiome with a significant increase in the abundance of the bacterial genus Helicobacter. The introduction of Helicobacter hepaticus to the gut of nonsusceptible mice was sufficient to drive macrophage expansion and MZ B cell development. Given that myeloid cells and MZ B cells are part of the first line of defense against blood-borne pathogens, their increase following a breach in the gut epithelial barrier would be protective. Thus, IL-10 is an essential gatekeeper that maintains immune homeostasis at distal sites that can become functionally imbalanced upon the introduction of specific pathogenic bacteria to the intestinal track.

Gut microbiota composition associated with alterations in cardiorespiratory fitness and psychosocial outcomes among breast cancer survivors.

PURPOSE: In this proof-of-concept pilot study, our purpose was to determine correlations between gut microbiota composition and alterations in cardiorespiratory fitness and psychosocial outcomes among post-primary treatment breast cancer survivors (BCS). METHODS: Composition of the gut microbiota in BCS (n = 12) was assessed at baseline (M0) and at the end of 3 months (M3) using Illumina MiSeq DNA Sequencing of the 16S rRNA gene. Gut microbiota composition was analyzed using the QIIME bioinformatics software and represented through diversity metrics and taxa analyses. Cardiorespiratory fitness, fatigue, anxiety, depression, and sleep dysfunction were assessed at M0 and M3 via the submaximal treadmill test, Fatigue Symptom Inventory, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index, respectively. RESULTS: Increased fatigue interference in BCS was associated with increased mean within-sample Shannon diversity (organism richness and evenness) (p = 0.009). Weighted UniFrac analysis (shifts in taxa relative abundance) revealed significant differences in between-sample (beta) diversity for changes in fatigue interference (p = 0.01) and anxiety (p = 0.022), with a trend observed for fatigue intensity and sleep dysfunction (p < 0.1). Unweighted UniFrac analysis (shifts in taxa types) found significant beta diversity differences for cardiorespiratory fitness (p = 0.026). Prior to false discovery correction (FDR), changes in fitness, fatigue, anxiety, and sleep dysfunction were associated with the frequency of certain gut bacteria genera (e.g., Faecalibacterium, Prevotella, Bacteroides) (p < 0.05). CONCLUSIONS: Correlations may exist between alterations in gut microbiota composition and longitudinal changes in cardiorespiratory fitness, fatigue, and anxiety in BCS. Further research examining the role of the microbiota-gut-brain axis in exercise-induced effects on psychosocial outcomes in BCS is warranted.

Response of germ-free mice to colonization with O. formigenes and altered Schaedler flora.

Colonization with Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stone disease. To improve our limited understanding of host/O.formigenes and microbe/O.formigenes interactions, germ-free or altered Schaedler flora (ASF) mice were colonized with O.formigenes Germ-free mice were stably colonized with O.formigenes suggesting O.formigenes does not require other organisms to sustain its survival. Examination of intestinal material indicated no viable O.formigenes in the small intestine, ∼4 × 106 O.formigenes per 100mg contents in the cecum and proximal colon, and ∼0.02% of total cecal O. formigenes cells were tightly associated to the mucosa. O.formigenes did not alter the overall microbial composition of ASF, and ASF did not impact O.formigenes capacity to degrade dietary oxalate in the cecum. 24-hour urine and fecal collections within metabolic cages in semi-rigid isolators demonstrated that introduction of ASF into germ-free mice significantly reduced urinary oxalate excretion. These experiments also showed that mono-colonized O.formigenes mice excrete significantly more urinary calcium compared to germ-free mice, which may be due to degradation of calcium oxalate crystals by O.formigenes and the subsequent intestinal absorption of free calcium. In conclusion, the successful establishment of defined-flora O.formigenes mouse models should improve our understanding of O.formigenes host and microbe interactions. These data support the use of O.formigenes as a probiotic that has limited impact on the composition of the resident microbiota but providing efficient oxalate degrading function. IMPORTANCE: Despite evidence suggesting a lack of O. formigenes colonization is a risk factor for calcium oxalate stone formation, little is known about O. formigenes biology. This study is the first to utilize germ-free mice to examine the response to mono-colonization with O. formigenes and the impact of a defined bacterial cocktail, altered Schaedler flora, on O. formigenes colonization. This study demonstrates that germ-free mice on their regular diet remain mono-colonized with O. formigenes, and suggests that further studies with O. formigenes gnotobiotic mouse models could improve our understanding of O. formigenes biology and host/O. formigenes and microbe/O. formigenes interactions.

Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile.

BACKGROUND: Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient's gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice. RESULTS: A total of nine samples from three human donors, recipient's pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01%). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8%, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55%, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2-4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7% of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10%. CONCLUSION: We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections.