A case-control study of the association between the gut microbiota and colorectal cancer: exploring the roles of diet, stress, and race.

BACKGROUND: The gut microbiota is associated with risk for colorectal cancer (CRC), a chronic disease for which racial disparities persist with Black Americans having a higher risk of CRC incidence and mortality compared to other groups. Given documented racial differences, the gut microbiota may offer some insight into previously unexplained racial disparities in CRC incidence and mortality. A case-control analysis comparing 11 women newly diagnosed with CRC with 22 cancer-free women matched on age, BMI, and race in a 1:2 ratio was conducted. Information about participants' diet and perceived stress levels were obtained via 24-h Dietary Recall and Perceived Stress Scale-10 survey, respectively. Participants provided stool samples from which microbial genomic DNA was extracted to reveal the abundance of 26 genera chosen a priori based on their previously observed relevance to CRC, anxiety symptoms, and diet. RESULTS: Significantly lower alpha diversity was observed among cancer-free Black women compared to all other race-cancer status combinations. No group differences were observed when comparing beta diversity. Non-Hispanic White CRC cases tended to have higher relative abundance of Fusobacteria, Gemellaceae, and Peptostreptococcus compared to all other race-cancer combination groups. Perceived stress was inversely associated with alpha diversity and was associated with additional genera. CONCLUSIONS: Our findings suggest that microbiome-CRC associations may differ by racial group. Additional large, racially diverse population-based studies are needed to determine if previously identified associations between characteristics of the gut microbiome and CRC are generalizable to Black women and other racial, ethnic, and gender groups.

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.

Factors Affecting the Gut Microbiome in Pediatric Intestinal Failure.

BACKGROUND: There is little data on gut microbiome and various factors that lead to dysbiosis in pediatric intestinal failure (PIF). This study aimed to characterize gut microbiome in PIF and determine factors that may affect microbial composition in these patients. METHODS: This is a single-center, prospective cohort study of children with PIF followed at our intestinal rehabilitation program. Stool samples were collected longitudinally at regular intervals over a 1-year period. Medical records were reviewed, and demographic and clinical data were collected. Medication history including the use of acid blockers, scheduled prophylactic antibiotics, and bile acid sequestrants was obtained. Gut microbial diversity among patients was assessed and compared according to various host characteristics of interest. RESULTS: The final analysis included 74 specimens from 12 subjects. Scheduled prophylactic antibiotics, presence of central line associated bloodstream infection (CLABSI) at the time of specimen collection, use of acid blockers, and ≥50% calories delivered via parenteral nutrition (PN) was associated with reduced alpha diversity, whereas increasing age was associated with improved alpha diversity at various microbial levels ( P value <0.05). Beta diversity differed with age, presence of CLABSI, use of scheduled antibiotics, acid blockers, percent calories via PN, and presence of oral feeds at various microbial levels ( P value <0.05). Single taxon analysis identified several taxa at several microbial levels, which were significantly associated with various host characteristics. CONCLUSION: Gut microbial diversity in PIF subjects is influenced by various factors involved in the rehabilitation process including medications, percent calories received parenterally, CLABSI events, the degree of oral feeding, and age. Additional investigation performed across multiple centers is needed to further understand the impact of these findings on important clinical outcomes in PIF.

A case-control study of the association between the gut microbiota and colorectal cancer: exploring the roles of diet, stress, and race.

Background: The gut microbiota is associated with risk for colorectal cancer (CRC), a chronic disease for which racial disparities persist with Black Americans having a higher risk of CRC incidence and mortality compared to other groups. Given documented racial differences, the gut microbiota may offer some insight into previously unexplained racial disparities in CRC incidence and mortality. A case-control analysis comparing 11 women newly diagnosed with CRC with 22 cancer-free women matched on age, BMI, and race in a 1:2 ratio was conducted. Information about participants' diet and perceived stress levels were obtained via 24-hour Dietary Recall and Perceived Stress Scale-10 survey, respectively. Participants provided stool samples from which microbial genomic DNA was extracted to reveal the abundance of 26 genera chosen a priori based on their previously observed relevance to CRC, anxiety symptoms, and diet. Results: Significantly lower alpha diversity was observed among cancer-free Black women compared to all other race-cancer status combinations. No group differences were observed when comparing beta diversity. Non-Hispanic White CRC cases tended to have higher relative abundance of Fusobacteria, Gemellaceae, and Peptostreptococcus compared to all other race-cancer combination groups. Perceived stress was inversely associated with alpha diversity and was associated with additional genera. Conclusions: Our findings suggest that microbiome-CRC associations may differ by racial group. Additional large, racially diverse population-based studies are needed to determine if previously identified associations between characteristics of the gut microbiome and CRC are generalizable to Black women and other racial, ethnic, and gender groups.

A modified standard American diet induces physiological parameters associated with metabolic syndrome in C57BL/6J mice.

Investigations into the causative role that western dietary patterns have on obesity and disease pathogenesis have speculated that quality and quantity of dietary fats and/or carbohydrates have a predictive role in the development of these disorders. Standard reference diets such as the AIN-93 rodent diet have historically been used to promote animal health and reduce variation of results across experiments, rather than model modern human dietary habits or nutrition-related pathologies. In rodents high-fat diets (HFDs) became a classic tool to investigate diet-induced obesity (DIO). These murine diets often relied on a single fat source with the most DIO consistent HFDs containing levels of fat up to 45-60% (kcal), higher than the reported human intake of 33-35% (kcal). More recently, researchers are formulating experimental animal (pre-clinical) diets that reflect mean human macro- and micronutrient consumption levels described by the National Health and Nutrition Examination Survey (NHANES). These diets attempt to integrate relevant ingredient sources and levels of nutrients; however, they most often fail to include high-fructose corn syrup (HFCS) as a source of dietary carbohydrate. We have formulated a modified Standard American Diet (mSAD) that incorporates relevant levels and sources of nutrient classes, including dietary HFCS, to assess the basal physiologies associated with mSAD consumption. Mice proffered the mSAD for 15 weeks displayed a phenotype consistent with metabolic syndrome, exhibiting increased adiposity, fasting hyperglycemia with impaired glucose and insulin tolerance. Metabolic alterations were evidenced at the tissue level as crown-like structures (CLS) in adipose tissue and fatty acid deposition in the liver, and targeted 16S rRNA metagenomics revealed microbial compositional shifts between dietary groups. This study suggests diet quality significantly affects metabolic homeostasis, emphasizing the importance of developing relevant pre-clinical diets to investigate chronic diseases highly impacted by western dietary consumption patterns.

Diet Quality and the Gut Microbiota in Women Living in Alabama.

INTRODUCTION: The gut microbiota is associated with obesity and modulated by individual dietary components. However, the relationships between diet quality and the gut microbiota and their potential interactions with weight status in diverse populations are not well understood. This study examined the associations between overall diet quality, weight status, and the gut microbiota in a racially balanced sample of adult females. METHODS: Female participants (N=71) residing in Birmingham, Alabama provided demographics, anthropometrics, biospecimens, and dietary data in this observational study from March 2014 to August 2014, and data analysis was conducted from August 2017 to March 2019. Weight status was defined as a BMI (weight [kg]/height [m2]) <30 kg/m2 for non-obese participants and ≥30 kg/m2 for participants who were obese. Dietary data collected included an Automated Self-Administered 24-Hour recall and Healthy Eating Index-2010 (HEI-2010) score. Diet quality was defined as having a high HEI score (≥median) or a low HEI score (

Comparison of the gut microbiome composition among individuals with acute or long-standing spinal cord injury vs. able-bodied controls.

Objective: Compare the gut microbiome composition among individuals with acute spinal cord injury (A-SCI), long-standing SCI (L-SCI), vs. able-bodied (AB) controls.Design: Cross-sectional study.Setting: The University of Alabama at Birmingham.Participants: Seven adults with A-SCI (36 ± 12 years, 2F/5M, C4-T10, and American Spinal Injury Association Impairment Scale [AIS] A-D), 25 with L-SCI (46 ± 13 years, 6F/19M, C4-L1, and AIS A-D), and 25 AB controls (42 ± 13 years, 9F/16M).Methods: Stool samples were collected after a median of 7 days and 18 years after injury in the A-SCI and L-SCI groups, respectively. Gut microbiome composition was analyzed using the 16S rRNA sequencing technique and QIIME software. The abundances of bacteria communities among groups were compared using the Kruskal-Wallis test adjusted for age.Results: Several alpha diversity indices were different among groups (Chao1, Observed species, and Phylogenetic Diversity), but not others (Shannon and Simpson). Beta diversity differed among each pair of groups (P < 0.05). A number of microbial communities were differentially abundant among the groups (P < 0.05).Conclusion: Our results revealed differences in the gut microbiome composition among groups. Compared to the AB controls, the SCI groups demonstrated microbiome profiles that shared features linked to metabolic syndrome, inflammation-related bowel disorders, depressive disorders, or antibiotics use, whereas the L-SCI group's microbiome included features linked to reduced physical activity compared to the A-SCI and AB controls. Our results provided preliminary data and a scientific foundation for future studies investigating the impact of the gut microbiome composition on long-term health in individuals with SCI.

The gut microbiome of extremely preterm infants randomized to the early progression of enteral feeding.

BACKGROUND: Early progression of feeding could influence the development of the gut microbiome. METHODS: We collected fecal samples from extremely preterm infants randomized to receive either early (feeding day 2) or delayed (feeding day 5) feeding progression. After study completion, we compared samples obtained at three different time points (week 1, week 2, and week 3) to determine longitudinal differences in specific taxa between the study groups using unadjusted and adjusted negative binomial and zero-inflated mixed models. Analyses were adjusted for a mode of delivery, breastmilk intake, and exposure to antibiotics. RESULTS: We analyzed 137 fecal samples from 51 infants. In unadjusted and adjusted analyses, we did not observe an early transition to higher microbial diversity within samples (i.e., alpha diversity) or significant differences in microbial diversity between samples (i.e., beta diversity) in the early feeding group. Our longitudinal, single-taxon analysis found consistent differences in the genera Lactococcus, Veillonella, and Bilophila between groups. CONCLUSIONS: Differences in single-taxon analyses independent of the mode of delivery, exposure to antibiotics, and breastmilk feeding suggest potential benefits of early progression of enteral feeding volumes. However, this dietary intervention does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02915549. IMPACT: Early progression of enteral feeding volumes with human milk reduces the duration of parenteral nutrition and the need for central venous access among extremely preterm infants. Early progression of enteral feeding leads to single-taxon differences in longitudinal analyses of the gut microbiome, but it does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Randomization in enteral feeding trials creates appealing opportunities to evaluate the effects of human milk diets on the gut microbiome.

High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling.

The neurobiological mechanisms that mediate psychiatric comorbidities associated with metabolic disorders such as obesity, metabolic syndrome and diabetes remain obscure. High fructose corn syrup (HFCS) is widely used in beverages and is often included in food products with moderate or high fat content that have been linked to many serious health issues including diabetes and obesity. However, the impact of such foods on the brain has not been fully characterized. Here, we evaluated the effects of long-term consumption of a HFCS-Moderate Fat diet (HFCS-MFD) on behavior, neuronal signal transduction, gut microbiota, and serum metabolomic profile in mice to better understand how its consumption and resulting obesity and metabolic alterations relate to behavioral dysfunction. Mice fed HFCS-MFD for 16 weeks displayed enhanced anxiogenesis, increased behavioral despair, and impaired social interactions. Furthermore, the HFCS-MFD induced gut microbiota dysbiosis and lowered serum levels of serotonin and its tryptophan-based precursors. Importantly, the HFCS-MFD altered neuronal signaling in the ventral striatum including reduced inhibitory phosphorylation of glycogen synthase kinase 3ß (GSK3ß), increased expression of ΔFosB, increased Cdk5-dependent phosphorylation of DARPP-32, and reduced PKA-dependent phosphorylation of the GluR1 subunit of the AMPA receptor. These findings suggest that HFCS-MFD-induced changes in the gut microbiota and neuroactive metabolites may contribute to maladaptive alterations in ventral striatal function that underlie neurobehavioral impairment. While future studies are essential to further evaluate the interplay between these factors in obesity and metabolic syndrome-associated behavioral comorbidities, these data underscore the important role of peripheral-CNS interactions in diet-induced behavioral and brain function. This study also highlights the clinical need to address neurobehavioral comorbidities associated with obesity and metabolic syndrome.

A Dietary Intervention High in Green Leafy Vegetables Reduces Oxidative DNA Damage in Adults at Increased Risk of Colorectal Cancer: Biological Outcomes of the Randomized Controlled Meat and Three Greens (M3G) Feasibility Trial.

Green leafy vegetables (GLV) may reduce the risk of red meat (RM)-induced colonic DNA damage and colorectal cancer (CRC). We previously reported the primary outcomes (feasibility) of a 12-week randomized controlled crossover trial in adults with habitual high RM and low GLV intake with body mass index (BMI) > 30 kg/m2 (NCT03582306). Herein, our objective was to report a priori secondary outcomes. Participants were recruited and enrolled in 2018, stratified by gender, and randomized to two arms: immediate intervention group (IG, n = 26) or delayed intervention group (DG, n = 24). During the 4 week intervention period, participants were provided with frozen GLV and counseled to consume 1 cooked cup equivalent daily. Participants consumed their normal diet for the remaining 8 weeks. At each of four study visits, anthropometrics, stool, and blood were taken. Overall, plasma Vitamin K1 (0.50 ± 1.18 ng/mL, p < 0.001) increased, while circulating 8OHdG (-8.52 ± 19.05 ng/mL, p < 0.001), fecal 8OHdG (-6.78 ± 34.86 ng/mL, p < 0.001), and TNFα (-16.95 ± 60.82 pg/mL, p < 0.001) decreased during the GLV intervention compared to control periods. Alpha diversity of fecal microbiota and relative abundance of major taxa did not differ systematically across study periods. Further investigation of the effects of increased GLV intake on CRC risk is warranted.

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.

Potential role for age as a modulator of oral nitrate reductase activity.

Reduction of salivary nitrate to nitrite by oral nitrate reductase (NR) expressing bacteria has emerged as an integral pathway in regulating nitric oxide (NO) homeostasis and signaling. The oral microbiome is critical for this pathway. Variations in this pathway may underlie variable responses in the magnitude by which dietary or therapeutic nitrate modulates NO-signaling. The relationships between oral microbes and NR activity, and the factors that affect this relationship remain unclear however. Using a cross-sectional study design, the objective of this study was to determine the relationships between oral microbes and oral NR activity using a protocol that directly measures initial NR activity. Tongue swabs were collected from 28 subjects ranging in age from 21 to 73y. Initial NR activity showed a bell-shaped dependence with age, with activity peaking at ~40-50y and being lower but similar between younger (20-30y) and older (51-73) individuals. Microbiome relative abundance and diversity analyses, using 16s sequencing, demonstrated differences across age and identified both NR expressing and non-expressing bacteria in modulating initial NR activity. Finally, initial NR activity was measured in 3mo and 13mo old C57BL/6J mice. No differences in bacterial number were observed. However initial NR activity was significantly (80%) lower in 13mo old mice. Collectively, these data suggest that age is a variable in NR activity and may modulate responsiveness to dietary nitrate.

Scheduled Empiric Antibiotics May Alter the Gut Microbiome and Nutrition Outcomes in Pediatric Intestinal Failure.

BACKGROUND: In this study, we aim to determine the effect of scheduled antibiotics on gut microbiome in pediatric intestinal failure (IF) and to evaluate the effect of the gut microbiome on nutrition outcomes in IF. METHODS: Fecal samples were collected at regular intervals from pediatric patients with IF for gut microbiome comparison between 2 cohorts: (group 1) those on scheduled prophylactic antibiotics and (group 2) those who were not on scheduled antibiotics. Gut microbiome composition and diversity were compared among the 2 cohorts. The association among gut microbiome composition, diversity, and nutrition outcomes (mainly ability to decrease parenteral nutrition [PN] energy requirement and ability to attain positive growth) was also determined. RESULTS: The microbiome of patients with IF on scheduled antibiotics differed significantly from those not on scheduled antibiotics. Abundance of certain Gram-negative and pathogenic bacteria (Pseudomonas, Prevotella, and Sutterella) was higher in the scheduled cohort. Patients with decreased Enterobacteriaceae demonstrated a greater ability to demonstrate a reduction in PN requirement, as well as attain positive growth. CONCLUSION: Scheduled antibiotics may alter the gut microbiome in children IF, which in turn may have an influence on important nutrition outcomes in pediatric IF. Further larger, multicenter studies are needed to determine the effect of scheduled antibiotics on the gut microbiome in this patient population and their overall effect on nutrition outcomes.

Age-Related Differences in the Gut Microbiome of Rhesus Macaques.

Aging is a multifactorial process characterized by progressive changes in gut physiology and the intestinal mucosal immune system. These changes, along with alterations in lifestyle, diet, nutrition, inflammation and immune function alter both composition and stability of the gut microbiota. Given the impact of environmental influences on the gut microbiota, animal models are particularly useful in this field. To understand the relationship between the gut microbiota and aging in nonhuman primates, we collected fecal samples from 20 male and 20 female rhesus macaques (Macaca mulatta), across the natural macaque age range, for 16S rRNA gene analyses. Operational taxonomic units were then grouped together to summarize taxon abundance at different hierarchical levels of classification and alpha- and beta-diversity were calculated. There were no age or sex differences in alpha diversity. At the phylum level, relative abundance of Proteobacteria and Firmicutes and Firmicutes to Bacteriodetes ratio were different between age groups though significance disappeared after correction for multiple comparisons. At the class level, relative abundance of Firmicutes_Bacilli decreased and Proteobacteria_Alphaproteobacteria and Proteobacteria_Betaproteobacteria increased with each successively older group. Only differences in Firmicutes_Bacilli remained significant after correction for multiple comparisons. No sex differences were identified in relative abundances after correction for multiple comparisons. Our results are not surprising given the known impact of environmental factors on the gut microbiota.

Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial.

BACKGROUND: Akkermansia muciniphila (AM) is a gram-negative, mucin-degrading bacteria inhabiting the gastrointestinal tract associated with host phenotypes and disease states. OBJECTIVE: Explore characteristics of overweight and obese female early-stage (0 to II) breast cancer patients with low AM relative abundance (LAM) vs high (HAM) enrolled in a presurgical weight-loss trial. DESIGN: Secondary analysis of pooled participants in a randomized controlled trial (NCT02224807). PARTICIPANTS/SETTING: During the period from 2014 to 2017, 32 female patients with breast cancer were randomized to weight-loss or attention-control arms from time of diagnosis-to-lumpectomy (mean=30±9 days). INTERVENTION: All were instructed to correct nutrient deficiencies via food sources and on upper-body exercises. The weight-loss group received additional guidance to promote 0.5 to 1 kg/wk weight-loss via energy restriction and aerobic exercise. MAIN OUTCOME MEASURES: At baseline and follow-up, sera, fecal samples, two-24 hour dietary recalls and dual x-ray absorptiometry were obtained. Bacterial DNA was isolated from feces and polymerase chain reaction (16S) amplified. Inflammatory cytokines were measured in sera. STATISTICAL ANALYSES PERFORMED: Differences between LAM and HAM participants were analyzed using t tests and nonparametric tests. Spearman correlations explored relationships between continuous variables. RESULTS: Participants were aged 61±9 years with body mass index 34.8±6. Mean AM relative abundance was 0.02% (0.007% to 0.06%) and 1.59% (0.59% to 13.57%) for LAM and HAM participants, respectively. At baseline, women with HAM vs LAM had lower fat mass (38.9±11.2 kg vs 46.4±9.0 kg; P=0.044). Alpha diversity (ie, species richness) was higher in women with HAM (360.8±84.8 vs 282.4±69.6; P=0.008) at baseline, but attenuated after weight-loss (P=0.058). At baseline, interleukin-6 level was associated with species richness (ρ=-0.471, P=0.008) and fat mass (ρ=0.529, P=0.002), but not AM. Change in total dietary fiber was positively associated with AM in LAM (ρ=0.626, P=0.002), but not HAM (ρ=0.436, P=0.180) participants. CONCLUSIONS: Among women with early-stage breast cancer, body composition is associated with AM, microbiota diversity, and interleukin-6 level. AM may mediate the effects of dietary fiber in improving microbiota composition.

Midtrimester microbial DNA variations in maternal serum of women who experience spontaneous preterm birth.

Objectives: To evaluate if midtrimester maternal serum contains microbial DNA and whether it differs between women with spontaneous preterm birth (SPTB) and those delivering at term.Study design: In this retrospective case-control study, we identified 20 healthy nulliparas with SPTB at 24-33 weeks of a nonanomalous singleton in 2014. Each case was matched by race/ethnicity to a control delivering at 39-40 weeks. Serum samples, collected at 15-20 weeks and stored at -80 C, were thawed and DNA extracted. PCR with primers targeting the 16S rDNA V4 region were used to prepare an amplicon library, sequenced using Illumina MiSeq, and analyzed using quantitative insight into microbial ecology (QIIME). Taxonomy was assigned using Ribosomal Database program (RDP) Classifier (threshold 0.8) against a modified Greengenes database. Differences in number of observed species, microbial alpha-diversity and beta-diversity, and taxa level analyses were undertaken.Results: All 40 samples were included. Women with SPTB had more unique observed species (p = .046) and higher mean alpha-diversity by Shannon index (but not Chao1 or Simpson) (p = .024). Microbial composition was different between groups by Bray-Curtis clustering (p = .03) but not by weighted (p = .13) or unweighted Unifrac (p = .11). Numerous taxa in the Firmicutes, Proteobacteria, and Actinobacteria phyla differed between groups (p < .05).Conclusions: SPTB is associated with distinct microbial DNA changes detected in midtrimester maternal serum.

Depletion of dietary aryl hydrocarbon receptor ligands alters microbiota composition and function.

The intestinal microbiota is critical for maintaining homeostasis. Dysbiosis, an imbalance in the microbial community, contributes to the susceptibility of several diseases. Many factors are known to influence gut microbial composition, including diet. We have previously shown that fecal immunoglobulin (Ig) A levels are decreased in mice fed a diet free of aryl hydrocarbon receptor (AhR) ligands. Here, we hypothesize this IgA decrease is secondary to diet-induced dysbiosis. We assigned mice to a conventional diet, an AhR ligand-free diet, or an AhR ligand-free diet supplemented with the dietary AhR ligand indole-3-carbinol (I3C). We observed a global alteration of fecal microbiota upon dietary AhR ligand deprivation. Compared to mice on the conventional diet, family Erysipelotrichaceae was enriched in the feces of mice on the AhR ligand-free diet but returned to normal levels upon dietary supplementation with I3C. Faecalibaculum rodentium, an Erysipelotrichaceae species, depleted its growth media of AhR ligands. Cultured fecal bacteria from mice on the AhR ligand-free diet, but not the other two diets, were able to alter IgA levels in vitro, as was F. rodentium alone. Our data point to the critical role of AhR dietary ligands in shaping the composition and proper functioning of gut microbiota.

Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio, leading to inflamed milieu in acute heart failure.

Calorie-dense obesogenic diet (OBD) is a prime risk factor for cardiovascular disease in aging. However, increasing age coupled with changes in the diet can affect the interaction of intestinal microbiota influencing the immune system, which can lead to chronic inflammation. How age and calorie-enriched OBD interact with microbial flora and impact leukocyte profiling is currently under investigated. Here, we tested the interorgan hypothesis to determine whether OBD in young and aging mice alters the gut microbe composition and the splenic leukocyte profile in acute heart failure (HF). Young (2-mo-old) and aging (18-mo-old) mice were supplemented with standard diet (STD, ∼4% safflower oil diet) and OBD (10% safflower oil) for 2 mo and then subjected to coronary artery ligation to induce myocardial infarction. Fecal samples were collected pre- and post-diet intervention, and the microbial flora were analyzed using 16S variable region 4 rRNA gene DNA sequencing and Quantitative Insights Into Microbial Ecology informatics. The STD and OBD in aging mice resulted in an expansion of the genus Allobaculum in the fecal microbiota. However, we found a pathologic change in the neutrophil:lymphocyte ratio in aging mice in comparison with their young counterparts. Thus, calorie-enriched OBD dysregulated splenic leukocytes by decreasing immune-responsive F4/80+ and CD169+ macrophages in aging mice. OBD programmed neutrophil swarming with an increase in isoprostanoid levels, with dysregulation of lipoxygenases, cytokines, and metabolite-sensing receptor expression. In summary, calorie-dense OBD in aging mice disrupted the composition of the gut microbiome, which correlates with the development of integrative and system-wide nonresolving inflammation in acute HF.-Kain, V., Van Der Pol, W., Mariappan, N., Ahmad, A., Eipers, P., Gibson, D. L., Gladine, C., Vigor, C., Durand, T., Morrow, C., Halade, G. V. Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio, leading to inflamed milieu in acute heart failure.