Many studies have examined the evolution of bacterial mutants that are resistant to specific antibiotics, and many of these focus on concentrations at and above the MIC. Here we ask for the minimum concentration at which existing resistant mutants can outgrow sensitive wild-type strains in competition experiments at antibiotic levels significantly below the MIC, and we define a minimum selective concentration (MSC) in Escherichia coli for two antibiotics, which is near 1/5 of the MIC for ciprofloxacin and 1/20 of the MIC for tetracycline. Because of the prevalence of resistant mutants already in the human microbiome, allowable levels of antibiotics to which we are exposed should be below the MSC. Since this concentration often corresponds to low or trace levels of antibiotics, it is helpful to have simple tests to detect such trace levels. We describe a simple ultrasensitive test for detecting the presence of antibiotics and genotoxic agents. The test is based on the use of chromogenic proteins as color markers and the use of single and multiple mutants of Escherichia coli that have greatly increased sensitivity to either a wide range of antibiotics or specific antibiotics, antibiotic families, and genotoxic agents. This test can detect ciprofloxacin at 1/75 of the MIC.

There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on the musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) that added to the diet protects female mice from musculoskeletal loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased the endogenous antioxidant response by bypassing the traditional antioxidant transcription factor Nrf2 and without activating estrogen receptor canonical signaling. Remarkably, Mont did not protect the male skeleton from androgen‐induced bone loss. Moreover, Mont increased the variety of bacterial communities in the gut microbiome (α‐diversity) more in female than in male mice; shifted the phylogenetic relatedness of bacterial communities (β‐diversity) further in females than males; and increased the prevalence of the taxon Ruminococcus1 in females but not males. Therefore, this nonpharmacologic intervention (i) protects from estrogen but not androgen deficiency; (ii) preserves bone, skeletal muscle, and body composition; (iii) elicits antioxidant defense responses independently of classical antioxidant/estrogenic signaling; and (iv) increases gut microbiome diversity toward a healthier signature. These findings highlight the impact of nutrition on musculoskeletal and gut microbiome homeostasis and support the precision medicine principle of tailoring dietary interventions to patient individualities, like sex. © 2020 American Society for Bone and Mineral Research (ASBMR).

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Epidemiological studies have shown associations between polyphenol-rich fruit intake and bone health, and preclinical studies have shown that blueberries improve bone health. To determine the genotype and dose of blueberries that are effective in ameliorating age-related bone loss, a multi-institutional team of investigators performed in vitro, preclinical, and clinical studies on blueberry varieties that differed in flavonoid profiles. Principal component analysis was used to select blueberry genotypes that varied in anthocyanin profiles. Total phenolic content did not predict the bioavailability of polyphenolic compounds in rats. A range in bioavailability was observed in individual polyphenolic compounds across genotypes. Both alpha and beta diversity analyses indicated that gut microbiome profiles varied with blueberry dose in rats. Additionally, the identification of specific taxa, such as Prevotellaceae_UCG-001 and Coriobacteriales, increasing after blueberry consumption adds to the mounting evidence of their role in polyphenol metabolism. All of the sources of variation can inform blueberry breeding practices to influence precision nutrition.

Objectives Determine the effects of an 8-wk chronic consumption of two different blueberry varieties at varying doses on calcium balance, calcium kinetics, bone microarchitecture and polyphenol metabolism and distribution in ovariectomized rats. Methods Eighty 5-mo old ovariectomized rats were sorted by weight and block-randomized to an 8-wk chronic feeding treatment of a polyphenol-free (control), 2.5% or 5% `Montgomery ́ (Mont) rabbiteye blueberry (V. ashei) or 5% wild lowbush blueberry (Wild BB) (V. angustifolium) (% w/w). During week 0 and week 8, rats went through a calcium balance study to determine calcium absorption and retention. At the end of week 8, rats were dosed with 45Ca and serial blood draws were done from baseline up to 48 h post-dose to map Ca kinetics. At sacrifice, the right femur was collected to determine differences in bone strength and microarchitecture of trabecular and cortical bone through MicroCT and a three-point bending test. A 24 h urine collection was done at baseline and during week 8 of treatment to determine urinary phenolic acid excretion and the left femur bone marrow phenolic acid accumulation through UPLC-MS/MS. Results A blueberry enriched diet had no effect on cortical bone microarchitecture, with a trend towards increased trabecular bone protection (p = 0.08). No differences were observed in bone strength. During baseline, a 2.5% Mont diet significantly increased Ca retention, but the effect was lost after the 8 weeks of treatment when rats had stabilized to treatment. Calcium kinetics showed that Mont 5% significantly increased Ca absorption and bone turnover (p < 0.05), while Mont 2.5% and Wild BB 5% did not. An accumulation of hippuric acid in the bone marrow was detected with the Mont blueberry treatments and it was significantly and positively correlated with bone deposition. The metabolism of phenolic acids was significantly affected by a chronic consumption of the treatment diets, resulting in significant phenolic acid profiles and excretion shifts. Conclusions A blueberry-enriched diet had minimal effects on bone after stabilized to ovariectomy and the effects differ depending on blueberry variety and dose. Funding Sources National Institute of Health (NIH) and National Center for Complementary and Integrative Health (NCCIH).