Abstract Racial health disparities persist among black and white women for colorectal cancer (CRC). Since the gut microbiota has been linked to CRC, understanding racial differences in the gut microbiota may yield new insight into unexplained disparities in CRC incidence. Generally healthy non-Hispanic black or white females who were at least 19 years old provided survey data, anthropometrics, and stool samples. Fecal DNA was collected and isolated from a wipe. PCR was used to amplify the V4 region of the 16SrRNA gene and 250 bases were sequenced using the MiSeq platform. Microbiome data were analyzed using the QIIME package. OTU data were log transformed and normalized. Linear models in R Package “limma” were used to test statistical significance differences. Fecal samples were analyzed for 80 females (47 black, 33 white). Mean age and BMI were 39.9 years and 30.1 kg/m2, respectively. Blacks had a higher average BMI than whites (33.3 vs. 27.5 kg/m2; p<0.01) and larger waist circumference (98.3 vs. 86.6 cm; p<0.01). Unadjusted comparisons revealed no racial differences in alpha diversity. Racial differences were observed in beta diversity and abundance of top-10 OTUs. Blacks had higher abundances than whites of Faecalibacterium (p=0.03) and Bacteroides (p=0.04). The association between race and Bacteroides (logFC=1.72; 0=0.02) persisted in fully adjusted models. Black race was associated with a higher abundance of Bacteroides, which has been linked to CRC. Other racial differences in the gut microbiota were also observed. Efforts to cultivate an “ideal” gut microbiota may help reduce CRC risk and health disparities. Citation Format: Tiffany L. Carson, Fuchenchu Wang, Xiangqin Cui, Bradford E. Jackson, Liam Van Der Pol, Elliot J. Lefkowitz, Casey Morrow, Monica Baskin. Racial comparisons of the gut microbiota of generally healthy black and white women for insights into colorectal cancer disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A59.
Human immunodeficiency virus (HIV-1) exclusively selects and utilizes tRNALys,3 as the primer for initiation of reverse transcription. Several elements within the TPsiC stem loop of tRNALys,3 are postulated to be important for selection and use in reverse transcription. The post-transcriptional modification at nucleotide 58 could play a role during plus-strand synthesis to stop reverse transcriptase from re-copying the tRNA primer. Nucleotides 53 and 54 within the TPsiC stem loop of the tRNA have been shown to be important to form the complex between tRNA and the HIV-1 viral genome during initiation of reverse transcription.To further delineate the features of the TPsiC stem loop of tRNALys,3 in reverse transcription, we have developed a complementation system in which E. coli tRNALys,3 is provided in trans to an HIV-1 genome in which the PBS is complementary to this tRNA. Successful selection and use of E. coli tRNALys,3 results in the production of infectious virus. We have used this single round infectious system to ascertain the effects that different mutants in the TPsiC stem loop of tRNALys,3 have on complementation. Mutants were designed within the TPsiC loop (nucleotide 58) and within the stem and loop of the TPsiC loop (nucleotides 53 and 54). Analysis of the expression of E. coli tRNALys,3 mutants revealed differences in the capacity for aminoacylation, which is an indication of intracellular stability of the tRNA. Alteration of nucleotide 58 from A to U (A58U), T54G and TG5453CC all resulted in tRNALys,3 that was aminoacylated when expressed in cells, while a T54C mutation resulted in a tRNALys,3 that was not aminoacylated. Both the A58U and T54G mutated tRNALys,3 complemented HIV-1 replication similar to wild type E. coli tRNALys,3. In contrast, the TG5453CC tRNALys,3 mutant did not complement replication.The results demonstrate that post-transcriptional modification of nucleotide 58 in tRNALys,3 is not essential for HIV-1 reverse transcription. In contrast, nucleotides 53 and 54 of tRNALys,3 are important for aminoacylation and selection and use of the tRNALys,3 in reverse transcription.
Metabolic disorders (e.g., impaired glucose tolerance, insulin resistance, and type 2 diabetes) are more prevalent in people with spinal cord injury (SCI) than able-bodied individuals. Dietary modification is a more cost-effective treatment option than pharmacological therapies for reducing the risk of metabolic dysfunction. Lowering carbohydrate, increasing protein, and maintaining a proper dietary fat intake are expected to induce favorable adaptations in glucose control, body fat distribution, and the composition of the gut microbiome. However, dietary modification has not been rigorously investigated in people with SCI. The purpose of this study is to determine if an 8-week low-carbohydrate/high-protein (LC/HP) dietary intervention will show improvements in clinically important metrics of metabolic function, body composition, the composition of gut bacteria, and quality of life. We intend to recruit 100 participants with chronic traumatic SCI (3 years postinjury, C5–L2, American Spinal Injury Association impairment scale A–D, and aged 18–65 years) and insulin resistance, impaired glucose tolerance or untreated type 2 diabetes and randomly assign them to an 8-week LC/HP dietary intervention group or a control group. The daily LC/HP dietary intervention includes ~ 30% total energy as protein (1.6 g/kg per day) with a carbohydrate-to-protein ratio < 1.5 and fat intake set at ~ 30% of the total energy intake. The control group does not receive any dietary intervention and are continuing with their regular daily diets. Glucose tolerance, insulin sensitivity, β-cell function, body composition, gut microbiome composition, and quality of life measures are assessed at week 1, before starting the LC/HP dietary intervention, and at week 8, after completion of the LC/HP dietary intervention. New information derived from this project will result in the development of a low-cost, simple, self-administered LC/HP dietary intervention for improving metabolic function in individuals with chronic SCI, improved understanding of the composition of gut bacteria in SCI, and how a LC/HP dietary intervention alters gut bacteria composition. In addition, this project will improve our understanding of the relationship between metabolic function and quality of life in individuals with long-standing SCI. ClinicalTrials.gov, NCT03207841 . Registered on 5 June 2017.
The B lymphocyte subpopulations producing immunoglobulin (Ig)E and the regulatory T cells modulating this IgE production in normals, and in atopic patients with respiratory allergy, atopic dermatitis, and markedly elevated serum IgE levels (>5,000 ng/ml), were investigated. Peripheral blood lymphocytes (PBL) were separated into T and B cell fractions and the ability of B cells to produce IgE in the presence or absence of pokeweed mitogen (PWM) and/or T cells ws determined. The patients had a circulating population of cells which spontaneously produced up to 6 ng of IgE in vitro (per 4 X 10(5) non-E-rosetting cells) in the absence of T lymphocytes and PWM. PBL from normals did not possess such cells. This IgE synthesis occurred primarily (>75%) over the first 72 h of culture. There was a wide range in their activity between patients and from the same patient studied on repeated occasions (from <300 to 6,000 pg per culture). This spontaneous IgE production was inhibited by PWM (mean inhibition, 37%) or normal T lymphocytes (mean inhibition, 42%). The patients lacked T lymphocytes capable of inhibiting this spontaneous IgE synthesis in 7 of 13 experiments. Functionally distinct B cells were identified in the patients and normals that responded to PWM with IgE production in vitro and required T-helper cell activity. Patients had normal PWM-responsive B cell IgE biosynthetic activity and T-helper function for these B cells. Suppressor T cell activity for PWM-driven IgE synthesis was also evaluated. Both the normals' and the patients' T lymphocytes provided similar levels of T cell suppressor function for PWM-driven IgE production. Patients with elevated serum IgE possessed these inhibitory T cells at times when the T lymphocytes which suppressed spontaneous igE production were absent from their PBL.
Background: Persons with dementia usually receive mouth care from nursing assistants. Inadequate mouth care causes poor oral health, a risk for systemic diseases like pneumonia. Nursing assistants struggle with balancing optimal mouth care against triggering care-resistant behaviors. Purpose: To evaluate the feasibility of a once-daily mouth care protocol on the outcomes of dental plaque and oral microbiome composition. Sample: Six nursing home residents with documented mouth care-resistant behavior: mean age was 66.3 years, 50% were African-American, and 50% were female. They all had moderate dementia and significant dental plaque (mean surface covered=50.7%, sd=20.8%) Methods: All subjects received 6 days of once-daily mouth care. Supragingival plaque and the anterior dorsum of the tongue were accessed for the microbiome samples, which were obtained before and after Day 1 and Day 6 mouth care activities. An intraoral camera (Soprocare™) was used to obtain video recorded images of all new plaque on all dentition before Day 1 mouth care and after Day 6 mouth care. Data Analysis: Plaque scores were analyzed using an adaptation of the Planimetric plaque index for 5 participants (one person’s decayed dentition precluded plaque measurements). Microbiome samples were descriptively analyzed at the genus level. Results: Mean plaque scores fell from 50.7% to 24%. Changes in tongue and plaque of at least 6% of the microbiome at the genus level were observed for Streptococcus, Veillonella, Prevotella, Haemophilus, and Rothia. Conclusion: Once-daily mouth care may be effective in reducing plaque and changing the oral microbiome composition.
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.
All pairwise comparisons were conducted between each post-FMT gnotobiotic dam (BRD) vs. their F1 progenies (F1-1, F1-2, F1-3, and F1-4). The resultant WSS scores are represented as a numerical value along with the data bar graphs. The WSS scores that were above the cut-off (CO) values are in red. CO: NA=no cut-off value assigned, thus excluded to distinguish a related strain pair.
