Microbial aromatic amino acid metabolism is modifiable in fermented food matrices to promote bioactivity.

Ingestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity relates to microbial metabolites derived from aromatic amino acids, termed aryl-lactates. Using targeted metabolomics, we established the presence of aryl-lactates in commercially available fermented foods. After pinpointing fermented food-associated lactic acid bacteria that produce high levels of aryl-lactates, we identified fermentation conditions to increase aryl-lactate production in food matrices up to 5 × 103 fold vs. standard fermentation conditions. Using ex vivo reporter assays, we found that food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and commercial products. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance AhR bioactivity of fermented foods to be leveraged to improve human health.

Acute Microbial Protease Supplementation Increases Net Postprandial Plasma Amino Acid Concentrations After Pea Protein Ingestion in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Digestibility is a primary factor in determining the quality of dietary protein. Microbial protease supplementation may be a strategy for improving protein digestion and subsequent postprandial plasma amino acid availability. OBJECTIVES: To assess the effect of co-ingesting a microbial protease mixture with pea protein on postprandial plasma amino acid concentrations. DESIGN: A mixture of 3 microbial protease preparations (P3) was tested for proteolytic efficacy in an in vitro static simulation of gastrointestinal digestion. Subsequently, in a randomized, double-blind, placebo-controlled crossover trial, 24 healthy adults (27 ± 4 y; 12 females, 12 males) ingested 25 g pea protein isolate (20 g protein, 2.2 g fat) with either P3 or maltodextrin placebo (PLA). Blood samples were collected at baseline and throughout a 0‒5 h postprandial period and both the early (0-2 h) iAUC and total (0-5 h) iAUC were examined. RESULTS: Plasma glucose concentrations decreased in both conditions (P < 0.001), with higher concentrations after P3 ingestion compared with PLA (P < 0.001). Plasma insulin concentrations increased for both conditions (P < 0.001) with no difference between conditions (P = 0.331). Plasma total amino acid (TAA) concentrations increased over time (P < 0.001) with higher concentrations observed for P3 compared with PLA (P = 0.010) during the 0‒5 h period. There was a trend for elevated essential amino acid (EAA) concentrations for P3 compared with PLA (P = 0.099) during the 0‒5 h postprandial period but not for leucine (P = 0.282) or branched-chain amino acids (BCAA, P = 0.410). The early net exposure (0‒2 h iAUC) to amino acids (leucine, BCAA, EAA, and TAA) was higher for P3 compared with PLA (all, P < 0.05). CONCLUSIONS: Microbial protease co-ingestion increases plasma TAA concentrations (0-5 h) and leucine, BCAA, EAA, and TAA availability in the early postprandial period (0‒2 h) compared with ingesting pea protein with placebo in healthy adults.

Postabsorptive and postprandial myofibrillar protein synthesis rates at rest and after resistance exercise in women with postmenopause.

Feeding and resistance exercise stimulate myofibrillar protein synthesis (MPS) rates in healthy adults. This anabolic characterization of "healthy adults" has been namely focused on males. Therefore, the purpose of this study was to examine the temporal responses of MPS and anabolic signaling to resistance exercise alone or combined with the ingestion of protein in postmenopausal females and compare postabsorptive rates with young females. Sixteen females [60 ± 7 yr; body mass index (BMI) = 26 ± 12 kg·m-2] completed an acute bout of unilateral resistance exercise before consuming either: a fortified whey protein supplement (WHEY) or water. Participants received primed continuous infusions of L-[ring-13C6]phenylalanine with bilateral muscle biopsies before and after treatment ingestion at 2 h and 4 h in nonexercised and exercised legs. Resistance exercise transiently increased MPS above baseline at 0-2 h in the water condition (P = 0.007). Feeding after resistance exercise resulted in a late phase (2-4 h) increase in MPS in the WHEY condition (P = 0.005). In both conditions, resistance exercise did not enhance the cumulative (0-4 h) MPS response. In the nonexercised leg, MPS did not differ at 0-2 h, 2-4 h, or 0-4 h of the measurement periods (all, P > 0.05). Likewise, there were no changes in the phosphorylation of p70S6K, AMPKα, or total and phosphorylated yes-associated protein on Ser127. Finally, postabsorptive MPS was lower in premenopausal versus postmenopausal females (P = 0.023). Our results demonstrate that resistance exercise-induced changes in MPS are temporally regulated, but do not result in greater cumulative (0-4 h) MPS in postmenopausal women.NEW & NOTEWORTHY An adequate quality and quantity of skeletal muscle is relevant to support physical performance and metabolic health. Muscle protein synthesis (MPS) is an established remodeling marker, which can be hypertrophic or nonhypertrophic. Importantly, protein ingestion and resistance exercise are two strategies that support healthy muscle by stimulating MPS. Our study shows postmenopause modulates baseline MPS that may diminish the MPS response to the fundamental anabolic stimuli of protein ingestion and resistance exercise in older females.

Ovarian antral follicles metabolize imidacloprid in vitro.

Neonicotinoid insecticides are synthetic nicotine derivatives that have high affinity for invertebrate nicotine receptors and low affinity for mammalian nicotine receptors. However, imidacloprid (IMI), the most commonly used neonicotinoid, can be bioactivated by the liver in mammals to desnitro-imidacloprid, an intermediate metabolite that effectively binds and activates mammalian receptors. However, it is not known if other tissues such as the ovaries can metabolize IMI. Thus, the present study tested the hypothesis that ovarian antral follicles metabolize and bioactivate IMI. Antral follicles were dissected from the ovaries of CD-1 mice and cultured in media containing dimethyl sulfoxide or IMI (0.2-200 µg/ml) for 48 and 96 h. Media were subjected to liquid chromatography-mass spectrometry for detection of phase I IMI metabolites. Follicles from the cultures were used for gene expression analysis of metabolic enzymes associated with IMI metabolism. All IMI metabolites were detected at 48 and 96 h. Oxidized IMI intermediates were detected in media from cultured follicles, but not environmental controls. Reduced IMI intermediates were detected in media from cultured follicles and the environmental controls. At 48 h, IMI did not affect expression of any metabolic enzymes compared with control. At 96 h, IMI induced Cyp2e1 and Cyp4f18 compared with control. These data indicate that mouse ovarian follicles metabolize IMI and that IMI induces ovarian Cyp expression over time.

Underpinning the Food Matrix Regulation of Postexercise Myofibrillar Protein Synthesis by Comparing Salmon Ingestion With the Sum of Its Isolated Nutrients in Healthy Young Adults.

BACKGROUND: Protein is most commonly consumed as whole foods as opposed to single nutrients. However, the food matrix regulation of the postprandial muscle protein synthetic response has received little attention. OBJECTIVES: The purpose of this study was to assess the effects of eating salmon (SAL) and of ingesting the same nutrients as an isolated mixture of crystalline amino acids and fish oil (ISO) on the stimulation of postexercise myofibrillar protein synthesis (MPS) and whole-body leucine oxidation rates in healthy young adults. METHODS: Ten recreationally active adults (24 ± 4 y; 5 men, 5 women) performed an acute bout of resistance exercise, followed by the ingestion of SAL or ISO in a crossover fashion. Blood, breath, and muscle biopsies were collected at rest and after exercise during primed continuous infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine. All data are presented as means ± SD and/or mean differences (95% CIs). RESULTS: Postprandial essential amino acid (EAA) concentrations peaked earlier (P = 0.024) in the ISO group than those in the SAL group. Postprandial leucine oxidation rates increased over time (P < 0.001) and peaked earlier in the ISO group (1.239 ± 0.321 nmol/kg/min; 63 ± 25 min) than those in the SAL group (1.230 ± 0.561 nmol/kg/min; 105 ± 20 min; P = 0.003). MPS rates for SAL (0.056 ± 0.022 %/h; P = 0.001) and ISO (0.046 ± 0.025 %/h; P = 0.025) were greater than the basal rates (0.020 ± 0.011 %/h) during the 0- to 5-h recovery period, with no differences between conditions (P = 0.308). CONCLUSION: We showed that the postexercise ingestion of SAL or ISO stimulate postexercise MPS rates with no differences between the conditions. Thus, our results indicate that ingesting protein from SAL as a whole-food matrix is similarly anabolic to ISO in healthy young adults. This trial was registered at www. CLINICALTRIALS: gov as NCT03870165.

Dual-laser self-injection locking to an integrated microresonator.

Diode laser self-injection locking (SIL) to a whispering gallery mode of a high quality factor resonator is a widely used method for laser linewidth narrowing and high-frequency noise suppression. SIL has already been used for the demonstration of ultra-low-noise photonic microwave oscillators and soliton microcomb generation and has a wide range of possible applications. Up to date, SIL was demonstrated only with a single laser. However, multi-frequency and narrow-linewidth laser sources are in high demand for modern telecommunication systems, quantum technologies, and microwave photonics. Here we experimentally demonstrate the dual-laser SIL of two multifrequency laser diodes to different modes of an integrated Si3N4 microresonator. Simultaneous spectrum collapse of both lasers, as well as linewidth narrowing and high-frequency noise suppression , as well as strong nonlinear interaction of the two fields with each other, are observed. Locking both lasers to the same mode results in a simultaneous frequency and phase stabilization and coherent addition of their outputs. Additionally, we provide a comprehensive dual-SIL theory and investigate the influence of lasers on each other caused by nonlinear effects in the microresonator.

Creatine Monohydrate Supplementation, but not Creatyl-L-Leucine, Increased Muscle Creatine Content in Healthy Young Adults: A Double-Blind Randomized Controlled Trial.

Creatine (Cr) supplementation is a well-established strategy to enhance gains in strength, lean body mass, and power from a period of resistance training. However, the effectiveness of creatyl-L-leucine (CLL), a purported Cr amide, is unknown. Therefore, the purpose of this study was to assess the effects of CLL on muscle Cr content. Twenty-nine healthy men (n = 17) and women (n = 12) consumed 5 g/day of either Cr monohydrate (n = 8; 28.5 ± 7.3 years, 172.1 ± 11.0 cm, 76.6 ± 10.7 kg), CLL (n = 11; 29.2 ± 9.3 years, 170.3 ± 10.5 cm, 71.9 ± 14.5 kg), or placebo (n = 10; 30.3 ± 6.9 years, 167.8 ± 9.9 cm, 69.9 ± 11.1 kg) for 14 days in a randomized, double-blind design. Participants completed three bouts of supervised resistance exercise per week. Muscle biopsies were collected before and after the intervention for quantification of muscle Cr. Cr monohydrate supplementation which significantly increased muscle Cr content with 14 days of supplementation. No changes in muscle Cr were observed for the placebo or CLL groups. Cr monohydrate supplementation is an effective strategy to augment muscle Cr content while CLL is not.

Canine urinary lactate and cortisol metabolites in hypercortisolism, nonadrenal disease, congestive heart failure, and health.

Spontaneous hypercortisolism (HC) is a common endocrine disease of senior dogs, often overlapping in selected clinical signs and hematologic and blood biochemical abnormalities with nonadrenal diseases (NADs). HC and NAD could differentially affect cortisol metabolism, which is a complex 10-enzymatic pathway process. HC might also affect blood and urine lactate levels through its effects on mitochondrial function. We aimed to differentiate between HC and NAD via a urinary cortisol metabolites and lactate panel. We prospectively recruited 7 healthy dogs and 18 dogs with HC, 15 with congestive heart failure (CHF), and 9 with NAD. We analyzed urine by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. We normalized urinary lactate and cortisol metabolites to urine creatinine concentration, and then compared groups using a linear-mixed model and principal component (PC) analysis. A machine-learning classification algorithm generated a decision tree (DT) model for predicting HC. The least-squares means of normalized urinary 6ß-hydroxycortisol and PC1 of the HC and CHF groups were higher than those of the healthy and NAD groups (p = 0.05). Creatinine-normalized urinary 6ß-hydroxycortisol had better sensitivity (Se, 0.78; 95% CI: 0.55-0.91), specificity (Sp, 0.89; 95% CI: 0.57-0.99), and a likelihood ratio (LR; 7), than the Se (0.72; 95% CI: 0.49-0.88), Sp (0.89; 95% CI: 0.57-0.99), and LR (6.5) of PC1 for distinguishing HC from NAD. Lactate and dihydrocortisone had the highest decreasing node-weighted impurity value and were considered the most important features in the DT model; dihydrocortisol had no role in determining whether a dog had HC.

Pharmacokinetic profiles of three dose rates of morphine sulfate following single intravenous, intramuscular, and subcutaneous administration in the goat.

This study aimed to evaluate pharmacokinetic profiles of morphine in goats following a single dose administered intravenously, intramuscularly, or subcutaneously at 0.1 mg/kg, 0.25 mg/kg, and 0.4 mg/kg. Study population included eight healthy adult goats in a randomized cross-over study. Serial plasma samples were collected and morphine was quantified using high-performance liquid chromatography/mass spectrometry. Data fit a two-compartment model following intravenous administration and a non-compartmental model following both intramuscular and subcutaneous administration. Plasma elimination half-life was 2.88 ± 1.13 h (0.1 mg/kg), 2.30 ± 0.49 h (0.25 mg/kg), and 2.67 ± 0.82 h (0.4 mg/kg) following IV morphine. Intramuscular Cmax values were 13.4 ± 2.77 ng/ml (0.1 mg/kg), 34 ± 11.50 ng/ml (0.25 mg/kg), and 68.9 ± 24.5 ng/ml (0.4 mg/kg). Intramuscular Tmax f(h) or IM dosing (in hrs) was 0.19 ± 0.14 (0.1 mg/kg), 0.24 ± 0.24 (0.25 mg/kg), and 0.21 ± 0.24 (0.4 mg/kg). Subcutaneous Cmax values were 9.88 ± 3.31 ng/ml (0.1 mg/kg), 28.5 ± 11.6 ng/ml (0.25 mg/kg), and 39.4 ± 14.3 ng/ml (0.4 mg/kg). Subcutaneous Tmax (h) values for SC dosing were 0.36 ± 0.21 (0.1 mg/kg), 0.31 ± 0.17 (0.25 mg/kg), and 0.4 ± 0.13 (0.4 mg/kg). Intramuscular bioavailability values were 153.77 ± 12.60% (0.4 mg/kg), 104.8 ± 25.12% (0.25 mg/kg), and 100.7 ± 29.57% (0.1 mg/kg). Subcutaneous bioavailability values were 130.58 ± 19.07% (0.4 mg/kg), 116.6 ± 27.03% (0.25 mg/kg), and 111.6 ± 23.24% (0.1 mg/kg). No adverse effects were observed. Assuming plasma concentration required to induce analgesia is 16 ± 9 ng/ml in goats, as demonstrated in humans, it is suggested to administer morphine intramuscularly at 0.4 mg/kg every 3-4 h or SC every 2-3 h. This is a speculative conclusion therefore further studies evaluating pharmacodynamics and plasma analgesic threshold in goats is recommended.

Why the Stall? Using metabolomics to define the lack of upstream movement of invasive bigheaded carp in the Illinois River.

Bigheaded Carp have spread throughout the Mississippi River basin since the 1970s. Little has stopped the spread as carp have the ability to pass through locks and dams, and they are currently approaching the Great Lakes. However, the location of the leading edge in the Illinois River has stalled for over a decade, even though there is no barrier preventing further advancement towards the Great Lakes. Defining why carp are not moving towards the Great Lakes is important for predicting why they might advance in the future. The aim of this study was to test the hypothesis that anthropogenic contaminants in the Illinois River may be playing a role in preventing further upstream movement of Bigheaded Carp. Ninety three livers were collected from carp at several locations between May and October of 2018. Liver samples were analyzed using gas chromatography-mass spectrometry in a targeted metabolite profiling approach. Livers from carp at the leading edge had differences in energy use and metabolism, and suppression of protective mechanisms relative to downstream fish; differences were consistent across time. This body of work provides evidence that water quality is linked to carp movement in the Illinois River. As water quality in this region continues to improve, consideration of this impact on carp spread is essential to protect the Great Lakes.

Impact of Weaning and Maternal Immune Activation on the Metabolism of Pigs.

Weaning wields environmental, social, and nutritional stresses that are detectable in the blood metabolite levels of the offspring. Prenatal stress in the form of maternal immune activation (MIA) in response to infection, which is associated with health and behavior disorders, also elicits prolonged changes in blood and brain cytokine and metabolite levels of the offspring. The goal of this study was to investigate the effects of weaning and MIA on the offspring's liver function to advance the understanding of the impact of stressors on peripheral and central nervous systems, physiology, and health. Gas chromatography-mass spectrometry analysis was used to compare the level of hepatic metabolites from 22-day-old pigs (n = 48) evenly distributed among weaning (nursed or weaned), viral MIA exposure (yes or no), and sexes. Weaning effects were detected on 38 metabolites at p-value < 0.05 (28 metabolites at FDR p-value < 0.05), and sex-dependent MIA effects were detected on 11 metabolites. Multiple intermediate and final products of the enriched (FDR p-value < 0.05) glycolysis and gluconeogenesis and pentose phosphate pathways were over-abundant in nursed relative to weaned pigs. The enriched pathways confirm the impact of weaning on hepatic metabolic shift, oxidative stress, and inflammation. Higher levels of the glucogenic amino acid histidine are observed in pigs exposed to MIA relative to controls, suggesting that the role of this metabolite in modulating inflammation may supersede the role of this amino acid as an energy source. The lower levels of cholesterol detected in MIA pigs are consistent with hypocholesterolemia profiles detected in individuals with MIA-related behavior disorders. Our findings underline the impact of weaning and MIA stressors on hepatic metabolites that can influence peripheral and central nervous system metabolic products associated with health and behavior disorders.

Early resistance training-mediated stimulation of daily muscle protein synthetic responses to higher habitual protein intake in middle-aged adults.

KEY POINTS: The ingestion of protein potentiates the stimulation of myofibrillar protein synthesis rates after an acute bout of resistance exercise. Protein supplementation (eating above the protein Recommended Dietary Allowance) during resistance training has been shown to maximize lean mass and strength gains in healthy young and older adults. Here, contractile, oxidative, and structural protein synthesis were assessed in skeletal muscle in response to a moderate or higher protein diet during the early adaptive phase of resistance training in middle-aged adults. The stimulation of myofibrillar, mitochondrial or collagen protein synthesis rates during 0-3 weeks of resistance training is not further enhanced by a higher protein diet. These results show that moderate protein diets are sufficient to support the skeletal muscle adaptive response during the early phase of a resistance training programme. ABSTRACT: Protein ingestion augments muscle protein synthesis (MPS) rates acutely after resistance exercise and can offset age-related loss in muscle mass. Skeletal muscle contains a variety of protein pools, such as myofibrillar (contractile), mitochondrial (substrate oxidation), and collagen (structural support) proteins, and the sensitivity to nutrition and exercise seems to be dependent on the major protein fraction studied. However, it is unknown how free-living conditions with high dietary protein density and habitual resistance exercise mediates muscle protein subfraction synthesis. Therefore, we investigated the effect of moderate (MOD: 1.06 ± 0.22 g kg-1  day-1 ) or high (HIGH: 1.55 ± 0.25 g kg-1  day-1 ) protein intake on daily MPS rates within the myofibrillar (MyoPS), mitochondrial (MitoPS) and collagen (CPS) protein fractions in middle-aged men and women (n = 20, 47 ± 1 years, BMI 28 ± 1 kg m-2 ) during the early phase (0-3 weeks) of a dietary counselling-controlled resistance training programme. Participants were loaded with deuterated water, followed by daily maintenance doses throughout the intervention. Muscle biopsies were collected at baseline and after weeks 1, 2 and 3. MyoPS in the HIGH condition remained constant (P = 1.000), but MOD decreased over time (P = 0.023). MitoPS decreased after 0-3 weeks when compared to 0-1 week (P = 0.010) with no effects of protein intake (P = 0.827). A similar decline with no difference between groups (P = 0.323) was also observed for CPS (P = 0.007). Our results demonstrated that additional protein intake above moderate amounts does not potentiate the stimulation of longer-term MPS responses during the early stage of resistance training adaptations in middle-aged adults.

Dileucine ingestion is more effective than leucine in stimulating muscle protein turnover in young males: a double blind randomized controlled trial.

Leucine is regarded as an anabolic trigger for the mTORC1 pathway and the stimulation muscle protein synthesis rates. More recently, there has been an interest in underpinning the relevance of branched-chain amino acid (BCAA)-containing dipeptides and their intact absorption into circulation to regulate muscle anabolic responses. We investigated the effects of dileucine and leucine ingestion on postprandial muscle protein turnover. Ten healthy young men (age: 23 ± 3 yr) consumed either 2 g of leucine (LEU) or 2 g of dileucine (DILEU) in a randomized crossover design. The participants underwent repeated blood and muscle biopsy sampling during primed continuous infusions of l-[ring-13C6]phenylalanine and l-[15N]phenylalanine to determine myofibrillar protein synthesis (MPS) and mixed muscle protein breakdown rates (MPB), respectively. LEU and DILEU similarly increased plasma leucine net area under the curve (AUC; P = 0.396). DILEU increased plasma dileucine AUC to a greater extent than LEU (P = 0.013). Phosphorylation of Akt (P = 0.002), rpS6 (P < 0.001), and p70S6K (P < 0.001) increased over time under both LEU and DILEU conditions. Phosphorylation of 4E-BP1 (P = 0.229) and eEF2 (P = 0.999) did not change over time irrespective of condition. Cumulative (0-180 min) MPS increased in DILEU (0.075 ± 0.032%·h-1), but not in LEU (0.047 ± 0.029%·h-1; P = 0.023). MPB did not differ between LEU (0.043 ± 0.030%·h-1) and DILEU conditions (0.051 ± 0.027%·h-1; P = 0.659). Our results showed that dileucine ingestion elevated plasma dileucine concentrations and muscle protein turnover by stimulating MPS in young men.NEW & NOTEWORTHY The role of dipeptides as anabolic agents remains unresolved in humans. We show that the ingestion of 2 g dileucine increased plasma dileucine concentrations and resulted in an enhancement of muscle protein turnover by stimulating an increase in muscle protein synthesis rates in healthy young males. The ingestion of 2 g leucine, however, did not stimulate an increase in muscle protein turnover. Our work provides the first insights into the effects of dipeptides on human protein metabolism.

Biogenic Amines Increase the Odds of Bacterial Vaginosis and Affect the Growth of and Lactic Acid Production by Vaginal Lactobacillus spp.

Bacterial vaginosis (BV) is the most common vaginal disorder of reproductive-aged women, yet its etiology remains enigmatic. One clinical symptom of BV, malodor, is linked to the microbial production of biogenic amines (BA). Using targeted liquid chromatography mass spectrometry, we analyzed 149 longitudinally collected vaginal samples to determine the in vivo concentrations of the most common BAs and then assessed their relationship to BV and effect upon the growth kinetics of axenically cultured vaginal Lactobacillus species. Increases in cadaverine, putrescine, and tyramine were associated with greater odds of women transitioning from L. crispatus-dominated vaginal microbiota to microbiota that have a paucity of Lactobacillus spp. and from Nugent scores of 0 to 3 to Nugent scores of 7 to 10, consistent with BV. Exposure to putrescine lengthened the lag time and/or slowed the growth of all vaginal Lactobacillus spp. except L. jensenii 62G. L. iners AB107's lag time was lengthened by cadaverine but reduced in the presence of spermidine and spermine. The growth rate of L. crispatus VPI 3199 was slowed by cadaverine and tyramine, and strain-specific responses to spermine and spermidine were observed. BAs were associated with reduced production of d- and l-lactic acid by vaginal Lactobacillus spp., and this effect was independent of their effect upon Lactobacillus species growth. The exceptions were higher levels of d- and l-lactic acid by two strains of L. crispatus when grown in the presence of spermine. Results of this study provide evidence of a direct impact of common biogenic amines on vaginal Lactobacillus spp.IMPORTANCELactobacillus spp. are credited with providing the primary defense against gynecological conditions, including BV, most notably through the acidification of the vaginal microenvironment, which results from their production of lactic acid. The microbial production of BAs has been hypothesized to play a mechanistic role in diminishing Lactobacillus species-mediated protection, enabling the colonization and outgrowth of diverse anaerobic bacterial species associated with BV. Here, we demonstrate that in vivo increases in the most commonly observed BAs are associated with a loss of Lactobacillus spp. and the development of BV, measured by Nugent score. Further, we show that BAs formed by amino acid decarboxylase enzymes negatively affect the growth of type strains of the most common vaginal Lactobacillus spp. and separately alter their production of lactic acid. These results suggest that BAs destabilize vaginal Lactobacillus spp. and play an important and direct role in diminishing their protection of the vaginal microenvironment.

The association of Chlamydia trachomatis and Mycoplasma genitalium infection with the vaginal metabolome.

Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) are two highly prevalent bacterial sexually transmitted infections (STIs) with a significant rate of co-infection in some populations. Vaginal metabolites are influenced by resident vaginal microbiota, affect susceptibility to sexually transmitted infections (STIs), and may impact local inflammation and patient symptoms. Examining the vaginal metabolome in the context of CT mono (CT+) and CT/MG co-infection (CT+/MG+) may identify biomarkers for infection or provide new insights into disease etiology and pathogenesis. Yet, the vaginal metabolome in the setting of CT infection is understudied and the composition of the vaginal metabolome in CT/MG co-infected women is unknown. Therefore, in this analysis, we used an untargeted metabolomic approach combined with 16S rRNA gene amplicon sequencing to characterize the vaginal microbiota and metabolomes of CT+, CT+/MG+, and uninfected women. We found that CT+ and CT+/MG+ women had distinct vaginal metabolomic profiles as compared to uninfected women both before and after adjustment for the vaginal microbiota. This study provides important foundational data documenting differences in the vaginal metabolome between CT+, CT+/MG+ and uninfected women. These data may guide future mechanistic studies that seek to provide insight into the pathogenesis of CT and CT/MG infections.

Ingestion of lean meat elevates muscle inositol hexakisphosphate kinase 1 protein content independent of a distinct post-prandial circulating proteome in young adults with obesity.

BACKGROUND: We have recently shown that a novel signalling kinase, inositol hexakisphosphate kinase 1 (IP6K1), is implicated in whole-body insulin resistance via its inhibitory action on Akt. Insulin and insulin like growth factor 1 (IGF-1) share many intracellular processes with both known to play a key role in glucose and protein metabolism in skeletal muscle. AIMS: We aimed to compare IGF/IP6K1/Akt signalling and the plasma proteomic signature in individuals with a range of BMIs after ingestion of lean meat. METHODS: Ten lean [Body mass index (BMI) (in kg/m2): 22.7 ±â€¯0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ±â€¯0.17], 10 overweight (BMI: 27.1 ±â€¯0.5; HOMAIR: 1.25 ±â€¯0.11), and 10 obese (BMI: 35.9 ±â€¯1.3; HOMAIR: 5.82 ±â€¯0.81) adults received primed continuous L-[ring-13C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at 0 min (post-absorptive), 120 min and 300 min relative to the ingestion of 170 g pork loin (36 g protein and 5 g fat) to examine skeletal muscle protein signalling, plasma proteomic signatures, and whole-body phenylalanine disappearance rates (Rd). RESULTS: Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = 0.056; 120 & 300 min, P > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 0.05). CONCLUSIONS: These data demonstrate, for the first time that muscle IP6K1 protein content is elevated after lean meat ingestion in obese adults, suggesting that IP6K1 may be contributing to the dysregulation of nutrient uptake in skeletal muscle. In addition, proteomic analysis showed no differences in proteomic signatures between obese, overweight or lean individuals.

Resistance Exercise-induced Regulation of Muscle Protein Synthesis to Intraset Rest.

During a traditional set configuration of resistance exercise (TRD), characterized by a continuous completion of repetitions, a decrease in power output tends to occur throughout a set of repetitions. Inclusion of intraset rest, otherwise known as a cluster set configuration (CLU), counteracts this power decline. However, the effect of a CLU configuration on postexercise myofibrillar protein synthesis rates (MPS) and anabolic signaling has not been investigated. PURPOSE: We aimed to determine if any mechanistic differences exist between TRD and CLU signaling events associated with muscle anabolism. METHODS: In randomized crossover trials, eight resistance-trained participants (23 ± 1 yr, 81 ± 4.7 kg, body fat: 18% ± 1.9%; 1 repetition maximum [1RM], 150 ± 9.1 kg) performed an acute bout of CLU (4 sets × (2 × 5) repetitions, 30-s intraset rest, 90-s interset rest) and TRD (4 sets × 10 repetitions, 120-s interset rest) barbell back squats at approximately 70% 1RM with total volume load equated during primed continuous L-[ring-C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at rest and after exercise at 0, 2, and 5 h. RESULTS: There was no difference in postexercise MPS between the CLU and TRD condition (P > 0.05) and no changes in phosphorylation of mTORC1 downstream targets (p70S6K and 4EBP1). Total and phosphorylated yes-associated protein on Ser127 transiently increased (P < 0.01) immediately after exercise (t = 0) in CLU (~2.1-fold) and TRD condition (~2.2-fold). CONCLUSIONS: Our results show that CLU is a viable anabolic option by preserving power output with similar MPS stimulation when compared with the TRD condition in trained young adults.

Potato ingestion is as effective as carbohydrate gels to support prolonged cycling performance.

Carbohydrate (CHO) ingestion is an established strategy to improve endurance performance. Race fuels should not only sustain performance but also be readily digested and absorbed. Potatoes are a whole-food-based option that fulfills these criteria, yet their impact on performance remains unexamined. We investigated the effects of potato purée ingestion during prolonged cycling on subsequent performance vs. commercial CHO gel or a water-only condition. Twelve cyclists (70.7 ± 7.7 kg, 173 ± 8 cm, 31 ± 9 yr, 22 ± 5.1% body fat; means ± SD) with average peak oxygen consumption (V̇o2peak) of 60.7 ± 9.0 mL·kg-1·min-1 performed a 2-h cycling challenge (60-85% V̇o2peak) followed by a time trial (TT; 6 kJ/kg body mass) while consuming potato, gel, or water in a randomized-crossover design. The race fuels were administered with [U-13C6]glucose for an indirect estimate of gastric emptying rate. Blood samples were collected throughout the trials. Blood glucose concentrations were higher (P < 0.001) in potato and gel conditions compared with water condition. Blood lactate concentrations were higher (P = 0.001) after the TT completion in both CHO conditions compared with water condition. TT performance was improved (P = 0.032) in both potato (33.0 ± 4.5 min) and gel (33.0 ± 4.2 min) conditions compared with water condition (39.5 ± 7.9 min). Moreover, no difference was observed in TT performance between CHO conditions (P = 1.00). In conclusion, potato and gel ingestion equally sustained blood glucose concentrations and TT performance. Our results support the effective use of potatoes to support race performance for trained cyclists.NEW & NOTEWORTHY The ingestion of concentrated carbohydrate gels during prolonged exercise has been shown to promote carbohydrate availability and improve exercise performance. Our study aim was to expand and diversify race fueling menus for athletes by providing an evidence-based whole-food alternative to the routine ingestion of gels during training and competition. Our work shows that russet potato ingestion during prolonged cycling is as effective as carbohydrate gels to support exercise performance in trained athletes.

Plasticity in the Human Gut Microbiome Defies Evolutionary Constraints.

The gut microbiome of primates, including humans, is reported to closely follow host evolutionary history, with gut microbiome composition being specific to the genetic background of its primate host. However, the comparative models used to date have mainly included a limited set of closely related primates. To further understand the forces that shape the primate gut microbiome, with reference to human populations, we expanded the comparative analysis of variation among gut microbiome compositions and their primate hosts, including 9 different primate species and 4 human groups characterized by a diverse set of subsistence patterns (n = 448 samples). The results show that the taxonomic composition of the human gut microbiome, at the genus level, exhibits increased compositional plasticity. Specifically, we show unexpected similarities between African Old World monkeys that rely on eclectic foraging and human populations engaging in nonindustrial subsistence patterns; these similarities transcend host phylogenetic constraints. Thus, instead of following evolutionary trends that would make their microbiomes more similar to that of conspecifics or more phylogenetically similar apes, gut microbiome composition in humans from nonindustrial populations resembles that of generalist cercopithecine monkeys. We also document that wild cercopithecine monkeys with eclectic diets and humans following nonindustrial subsistence patterns harbor high gut microbiome diversity that is not only higher than that seen in humans engaging in industrialized lifestyles but also higher compared to wild primates that typically consume fiber-rich diets.IMPORTANCE The results of this study indicate a discordance between gut microbiome composition and evolutionary history in primates, calling into question previous notions about host genetic control of the primate gut microbiome. Microbiome similarities between humans consuming nonindustrialized diets and monkeys characterized by subsisting on eclectic, omnivorous diets also raise questions about the ecological and nutritional drivers shaping the human gut microbiome. Moreover, a more detailed understanding of the factors associated with gut microbiome plasticity in primates offers a framework to understand why humans following industrialized lifestyles have deviated from states thought to reflect human evolutionary history. The results also provide perspectives for developing therapeutic dietary manipulations that can reset configurations of the gut microbiome to potentially improve human health.