Serum Amino Acid Research Articles

Circulating amino acids and acylcarnitines correlated with different CAC score ranges in diabetic postmenopausal women using LC–MS/MS based metabolomics approach

BackgroundDiabetes mellitus (DM) and its cardiovascular disease (CVD) complication are among the most frequent causes of death worldwide. However, the metabolites linking up diabetes and CVD are less understood. In this study, we aimed to evaluate serum acylcarnitines and amino acids in postmenopausal women suffering from diabetes with different severity of CVD and compared them with healthy controls.MethodsThrough a cross-sectional study, samples were collected from postmenopausal women without diabetes and CVD as controls (n = 20), patients with diabetes and without CVD (n = 16), diabetes with low risk of CVD (n = 11), and diabetes with a high risk of CVD (n = 21) referred for CT angiography for any reason. Metabolites were detected by a targeted approach using LC–MS/MS and metabolic -alterations were assessed by applying multivariate statistical analysis. The diagnostic ability of discovered metabolites based on multivariate statistical analysis was evaluated by ROC curve analysis.ResultsThe study included women aged from 50–80 years with 5–30 years of menopause. The relative concentration of C14:1, C14:2, C16:1, C18:1, and C18:2OH acylcarnitines decreased and C18 acylcarnitine and serine increased in diabetic patients compared to control. Besides, C16:1 and C18:2OH acylcarnitines increased in high-risk CVD diabetic patients compared to no CVD risk diabetic patients.ConclusionDysregulation of serum acylcarnitines and amino acids profile correlated with different CAC score ranges in diabetic postmenopausal women. (Ethic approval No: IR.TUMS.EMRI.REC.1399.062).

Characterizing serum amino acids in schizophrenic patients: Correlations with gut microbes

Amino acid abnormalities have been suggested to be a key pathophysiological mechanism in schizophrenia (SZ). Recently, gut microbes were found to be critically involved in mental and metabolic diseases. However, the relationship between serum amino acid levels and gut microbes in SZ is rarely studied. Here, we analyzed serum amino acid levels in 76 untreated SZ patients and 79 healthy controls (HC). Serum levels of 10 amino acids were significantly altered in patients with SZ. We further classified the cut-off values for serum arginine, leucine, glutamine, and methionine levels to distinguish SZ patients from controls. These classifiers were shown to be effective in another validation cohort (49 SZ and 48 HC). The correlation between serum amino acids and clinical symptoms and cognitive functions was also analyzed. Arginine, leucine, glutamine, and methionine levels were significantly correlated with clinical symptoms and cognitive impairments in SZ patients. By metagenome shotgun sequencing of fecal samples, we found that patients with SZ with a low level of serum amino acids have higher richness and evenness of the gut microbiota. At the genus level, the abundances of Mitsuokella and Oscillibacter are significantly abnormal. At the mOTU level, 15 mOTUs in the low-level SZ group were significantly different from the HC group. In addition, Mitsuokella multacida was correlated with glutamine and methionine, respectively. Our research revealed that alterations in serum amino acid levels are critically related to changes in gut microbiota composition in SZ patients. These findings may shed light on new strategies for the diagnosis and treatment of SZ.

Associations of serum amino acids with insulin resistance among people with and without overweight or obesity: A prospective study in Japan

Limited evidence exists regarding the prospective associations between amino acids and insulin resistance. In addition, amino acids have been suggested to promote insulin resistance with the requirement of obesity in animal studies, but the interaction between amino acids and obesity on the development of insulin resistance has not been examined in epidemiological studies. We aimed to investigate the differences in the prospective associations of serum amino acids with insulin resistance among adults with and without overweight or obesity. Fasting serum concentrations of 25 amino acids were quantified in 1131 non-diabetic Japanese workers aged 22-71 years at baseline. The homeostasis model assessment of insulin resistance (HOMA-IR) was estimated at baseline and the 3-year follow-up. Generalized linear models were used to assess the associations between amino acids at baseline and HOMA-IR at follow-up with adjustment for potential confounding factors. A Bonferroni-corrected threshold of p=0.001 was considered significant for multiple tests. The associations for the following amino acids with HOMA-IR at the 3-year follow-up significantly varied by obesity status: isoleucine, valine, tyrosine, alanine, and methionine (all p for interaction <0.05). Higher concentrations of serum isoleucine, valine, tyrosine, and alanine (per 1SD) were significantly associated with higher HOMA-IR levels in overweight/obese participants (multivariable-adjusted β coefficients ranging from 0.09 to 0.12; all p<0.001), but no association was observed in the underweight/normal-weight participants. The associations for serum methionine were direct among overweight/obese participants, but inverse among underweight/normal-weight participants (all p<0.001). This study demonstrated the prospective associations of different individual serum amino acids with insulin resistance, with most pronounced associations being for overweight/obese adults. Our findings support the possibility of heterogeneous effects of individual amino acids, as well as their interplay with obesity in the progression of insulin resistance.

Initial military training modulates serum fatty acid and amino acid metabolites.

Initial military training (IMT) results in increased fat‐free mass (FFM) and decreased fat mass (FM). The underlying metabolic adaptations facilitating changes in body composition during IMT are unknown. The objective of this study was to assess changes in body composition and the serum metabolome during 22‐week US Army IMT. Fifty‐four volunteers (mean ± SD; 22 ± 3 year; 24.6 ± 3.7 kg/m2) completed this longitudinal study. Body composition measurements (InBody 770) and blood samples were collected under fasting, rested conditions PRE and POST IMT. Global metabolite profiling was performed to identify metabolites involved in energy, carbohydrate, lipid, and protein metabolism (Metabolon, Inc.). There was no change in body mass (POST‐PRE; 0.4 ± 5.1 kg, p = 0.59), while FM decreased (−1.7 ± 3.5 kg, p < 0.01), and FFM increased (2.1 ± 2.8 kg, p < 0.01) POST compared to PRE IMT. Of 677 identified metabolites, 340 differed at POST compared to PRE (p < 0.05, Q < 0.10). The majority of these metabolites were related to fatty acid (73%) and amino acid (26%) metabolism. Increases were detected in 41% of branched‐chain amino acid metabolites, 53% of histidine metabolites, and 35% of urea cycle metabolites. Decreases were detected in 93% of long‐chain fatty acid metabolites, while 58% of primary bile acid metabolites increased. Increases in amino acid metabolites suggest higher rates of protein turnover, while changes in fatty acid metabolites indicate increased fat oxidation, which likely contribute changes in body composition during IMT. Overall, changes in metabolomics profiles provide insight into metabolic adaptions underlying changes in body composition during IMT.

Essential and Non-Essential Amino Acids in Dogs at Different Stages of Chronic Kidney Disease.

Simple SummaryHuman patients affected by chronic kidney disease reported alterations of serum amino acid pattern, as a consequence of several metabolic complications of the renal disease. Our study aimed to evaluate possible differences in serum pattern of essential and non-essential amino acids between dogs with chronic kidney disease and clinically healthy subjects. Canine chronic kidney disease resulted in an association with a significant serum deficiency of the majority of both essential and non-essential amino acids. The amino-acidic disorder was particularly evident when protein-energy wasting syndrome was present, suggesting a potential key role of pathological conditions, such as inflammation, insulin resistance, and increased protein breakdown.Abnormalities of serum amino acid profile, mostly characterized by a reduction in essential amino acids (EAAs) and an increase in non-essential amino acids (NEAAs), have been documented in human chronic kidney diseases (CKD). Amino acid disorders have been associated with CKD complications, such as metabolic acidosis and malnutrition. The aim of the present study was to evaluate EAAs and NEAAs in dogs affected by CKD at different IRIS stages, with particular reference to calcium–phosphate abnormalities, metabolic acidosis, and protein-energy wasting syndrome (PEW). Serum EAAs (L-histidine, L-isoleucine, L-leucine, L-lysine, methionine, L-phenylalanine, L-threonine, tryptophan, L-valine, and L-arginine) and serum NEAAs (L-alanine, L-aspartic acid, L-cysteine, L-glutamic acid, glycine, proline, L-serine, and L-tyrosine) were analyzed with HPLC in a group of dogs with CKD (n = 62), and in a group of healthy dogs (n = 25). CKD dogs showed significantly lower serum levels of histidine (p < 0.000), isoleucine (p < 0.000), tryptophan (p < 0.000), alanine (p = 0.013), cysteine (p < 0.000), and serine (p = 0.002), and significantly higher levels of proline (p < 0.000), leucine (p = 0.001), lysine (p < 0.000), valine (p < 0.000), arginine (p = 0.002), glutamic acid (p = 0.002), and glycine (p = 0.010) compared to healthy dogs. Dogs with abnormal calcium x phosphate values showed significantly higher levels of cysteine (p = 0.003), and lower levels of tryptophan (p = 0.025) compared to CKD dogs with normal CaxP. Dogs with metabolic acidosis showed significantly higher levels of phenylalanine (p = 0.035) and leucine (p = 0.034) compared to CKD dogs without metabolic acidosis. Dogs with PEW showed significantly lower levels for most of amino acids. In PEW dogs, the median distribution of both EAAs (p = 0.000) and NEAAs (p = 0.001) was significantly lower. The serum pattern of both EAAs and NEAAs was significantly different in CKD dogs compared to healthy dogs, although no association with the progression of the IRIS stage was found.

Combined Oral Contraceptive Treatment Does Not Alter the Gut Microbiome but Affects Amino Acid Metabolism in Sera of Obese Girls With Polycystic Ovary Syndrome.

Background: The gut microbiome is altered in obese adolescents with polycystic ovary syndrome (PCOS), and is associated with free testosterone, metabolic markers, and insulin resistance. Combined oral contraceptives (OCP) are a primary treatment for PCOS and decrease testosterone, but the effect on the serum metabolome or gut microbiome in obese adolescents with PCOS is unknown. Objective: Contrast gut microbiome profiles, targeted serum metabolomics, hormone levels, and metabolic measures in adolescents with PCOS and obesity with and without OCP treatment. Methods: Adolescent girls with obesity and PCOS underwent stool and fasting blood collection and MRI for hepatic fat fraction. Fecal bacteria were profiled by high-throughput 16S rRNA gene sequencing and fasting serum metabolomics performed with high resolution mass spectrometry. Groups were contrasted using t-tests and principle least squares discrimination analysis (PLS-DA). Associations between bacterial taxa, baseline metabolic measures, hormone levels and the metabolome were conducted using Spearman analysis. Analyses were adjusted for false discovery rate. Results: 29 adolescents with obesity [Untreated N = 21, 16 ± 1.2 years, BMI%ile 36.5 ± 3.0; OCP N = 8, 15.5 ± 0.9 years, BMI%ile 32.5 ± 3.9] participated. Of the untreated adolescents, N = 14 contributed serum for metabolomic analysis. Participants on OCP therapy had lower free testosterone and free androgen index (p < 0.001) and higher sex hormone binding globulin. There was no difference in measures of fasting glucose, insulin, lipids or HOMA-IR between groups. PLS-DA of serum metabolomics showed discrimination between the groups, secondary amino acid changes. Untreated and OCP had similar stool microbiome α-diversity based on evenness (p = 0.28), richness (p = 0.39), and Shannon diversity (p = 0.24) and global microbial composition (β-diversity, p = 0.56). There were no differences in % relative abundance at any level. Bacterial α-diversity was negatively associated with serum long chain fatty acids and branched chain amino acids. A higher %relative abundance of family Ruminococcaceae was significantly associated with serum bile acids and HOMA-IR. Conclusion: Despite hormone and serum amino acid differences, girls treated with OCP had similar metabolic and gut microbiome profiles compared to the untreated PCOS group. The association between bacterial α-diversity, Ruminococcaceae, clinical markers and long chain fatty acids suggests a potential role of the gut microbiome in the pathogenesis of the metabolic comorbidities in PCOS.

Serum Amino Acid Profile Changes After Repetitive Breath-Hold Dives: A Preliminary Study

BackgroundThe aim of this work was to investigate the serum amino acid (AA) changes after a breath-hold diving (BH-diving) training session under several aspects including energy need, fatigue tolerance, nitric oxide (NO) production, antioxidant synthesis and hypoxia adaptation. Twelve trained BH-divers were investigated during an open sea training session and sampled for blood 30 min before the training session, 30 min and 4 h after the training session. Serum samples were assayed for AA changes related to energy request (alanine, histidine, isoleucine, leucine, lysine, methionine, proline threonine, valine), fatigue tolerance (ornithine, phenylalanine, tyrosine), nitric oxide production (citrulline), antioxidant synthesis (cystine, glutamate, glycine) and hypoxia adaptation (serine, taurine).Main resultsConcerning the AA used as an energy support during physical effort, we found statistically significant decreases for all the investigated AA at T1 and a gradual return to the basal value at T2 even if alanine, proline and theonine still showed a slight significant reduction at this time. Also, the changes related to the AA involved in tolerance to physical effort showed a statistically significant decrease only at T1 respect to pre-diving value and a returned to normal value at T2. Citrulline, involved in NO production, showed a clear significant reduction both at T1 and T2. Concerning AA involved in endogenous antioxidant synthesis, the behaviour of the three AA investigated is different: we found a statistically significant increase in cystine both at T1 and T2, while glycine showed a statistically significant reduction (T1 and T2). Glutamate did not show any statistical difference. Finally, we found a statistically significant decrease in the AA investigated in other hypoxia conditions serine and taurine (T1 and T2).ConclusionsOur data seem to indicate that the energetic metabolic request is in large part supported by AA used as substrate for fuel metabolism and that also fatigue tolerance, NO production and antioxidant synthesis are supported by AA. Finally, there are interesting data related to the hypoxia stimulus that indirectly may confirm that the muscle apparatus works under strong exposure conditions notwithstanding the very short/low intensity of exercise, due to the intermittent hypoxia caused by repetitive diving.

The Association of Circulating Amino Acids and Dietary Inflammatory Potential with Muscle Health in Chinese Community-Dwelling Older People.

Amino acids (AAs) and dietary inflammatory potential play essential roles in muscle health. We examined the associations of dietary inflammatory index (DII) of habitual diet with serum AA profile, and ascertained if the associations between DII and muscle outcomes were mediated by serum AAs, in 2994 older Chinese community-dwelling men and women (mean age 72 years) in Hong Kong. Higher serum branched chain AAs (BCAAs), aromatic AAs and total glutathione (tGSH) were generally associated with better muscle status at baseline. A more pro-inflammatory diet, correlating with higher serum total homocysteine and cystathionine, was directly (90.2%) and indirectly (9.8%) through lower tGSH associated with 4-year decline in hand grip strength in men. Higher tGSH was associated with favorable 4-year changes in hand grip strength, gait speed and time needed for 5-time chair stands in men and 4-year change in muscle mass in women. Higher leucine and isoleucine were associated with decreased risk of sarcopenia in men; the associations were abolished after adjustment for BMI. In older men, perturbations in serum sulfur AAs metabolism may be biomarkers of DII related adverse muscle status, while the lower risk of sarcopenia with higher BCAAs may partly be due to preserved BMI.

A Newly Developed Indicator of Overeating Saturated Fat Based on Serum Fatty Acids and Amino Acids and Its Association With Incidence of Type 2 Diabetes: Evidence From Two Randomized Controlled Feeding Trials and a Prospective Study.

ObjectiveHyper-caloric intake of saturated fatty acids (SFAs) is common in modern societies, probably contributing to the epidemic of type 2 diabetes mellitus (T2DM). This study conducted two randomized controlled trials (RCTs) for developing a new indicator that can assess the nutritional status and examined its association with incidence of T2DM.MethodsIn RCT 1, healthy participants were randomly assigned into three groups, namely, control group (n = 40), overfeeding group 1 (100 g butter per day, n = 37), and overfeeding group 2 (120 g butter per day, n = 37). In RCT 2, healthy subjects were randomly assigned into two groups, namely, control group (n = 52) and high-fat group (300-extra kcal/day from diet that was designed by high-fat diet, n = 58). In the prospective cohort, 4,057 participants aged 20–74 years were enrolled and followed up over 5.3 years. Serum profiles of fatty acids and amino acids were measured.ResultsIn RCT 1, serum fatty acids, including C14:0 and C18:0, increased, whereas C18:2, C20:4, C22:5, and C22:6 decreased; serum amino acids, including tyrosine, alanine, and aminobutyric acid, increased, whereas histidine and glycine decreased (p < 0.05). Among these serum fatty acids and amino acids, changes in C14:0, C20:4, tyrosine, histidine, and glycine were also observed in RCT 2. An indicator was developed based on the five fatty acids and amino acids, namely, C14:0 × tyrosine × 1,000/[C20:4 × (glycine + histidine)], and it significantly identified participants in the intervention group with area under the curve (AUC) (95% CI) being 0.85 (0.77–0.92). The indicator was significantly associated with incidence of T2DM in the prospective cohort with HRs (95% CIs) from bottom quartile to top quartile being 1,1.21 (0.82–1.77), 1.60 (1.12–2.30), 2.04 (1.42–2.94).ConclusionThe newly developed indicator in RCTs can be used in assessing the nutritional status of hypercaloric intake of SFA and predicting the development of T2DM.

Effects of Dietary Fiber, Crude Protein Level, and Gestation Stage on the Nitrogen Utilization of Multiparous Gestating Sows

Simple SummaryTwo major concerns for sustainable swine production are the shortage of protein feed resources and the excretion of nitrogen and phosphorus into the environment. Those concerns can be partly alleviated by increasing nitrogen utilization by improving nutrition for pigs. This study observed that a low crude protein and dietary fiber supplemented diet can improve nitrogen utilization and reduce urinary nitrogen excretion. Additionally, late gestating sows have greater nitrogen utilization than those of early gestation, characterized by reduced nitrogen in urine and lower amino acids in serum. These findings offer nutritional solutions for improving nitrogen utilization.To investigate the effects of dietary fiber (DF), crude protein (CP) level, and gestation stage on nitrogen utilization, 28 Landrace-Yorkshire cross gestating sows at parity two were randomly divided into four dietary treatments with seven duplicates of one pig with a repeated-measures design. The diets comprised one with normal crude protein (CP) of 13.3%, one with a low CP diet of 10.1%, and two diets, one with dietary fiber (DF) supplementation of inulin and cellulose at the ratio of 1:1 and one without DF. The total litter size, litter size alive, and newborn birthweight of piglets did not differ between treatment groups. Sows that received high DF levels had greater nitrogen output in feces, lower urinary nitrogen, and increased nitrogen retention. Sows that received a low CP diet had reduced nitrogen excretion in feces and urine, lower nitrogen retention, and an unchanged nitrogen retention ratio. Sows at the late stage of gestation on days 95 to 98 had lower nitrogen excretion in urine and greater nitrogen retention than in the early stage of gestation on days 35 to 38, associated with a significant decrease in serum amino acids in late gestation. Maternal protein deposition was increased by high DF, decreased by low CP, and lower in late gestation compared with early gestation. Collectively, DF improved nitrogen utilization by decreasing urine nitrogen output, and nitrogen utilization increased as gestation advanced.

Effects of a Novel High-Quality Protein Infant Formula on Energetic Efficiency and Tolerance: A Randomized Trial.

Objectives:Protein overfeeding in infants can have negative effects, such as diabetes and childhood obesity; key to reducing protein intake from formula is improving protein quality. The impact of a new infant formula [study formula (SF)] containing alpha-lactalbumin, lactoferrin, partially hydrolyzed whey, and whole milk on growth and tolerance compared to a commercial formula (CF) and a human milk reference arm was evaluated.Methods:This randomized, double-blind trial included healthy, singleton, term infants, enrollment age ≤14 days. Primary outcome was mean daily weight gain. Secondary outcomes were anthropometrics, formula intake, serum amino acids, adverse events, gastrointestinal characteristics, and general disposition.Results:Non-inferiority was demonstrated. There were no differences between the formula groups for z scores over time. Formula intake [−0.33 oz/kg/day, 95% confidence interval (CI): −0.66 to −0.01, P = 0.05] and mean protein intake (−0.13 g/kg/day, 95% CI: −0.26 to 0.00, P = 0.05) were lower in the SF infants, with higher serum essential amino acid concentrations (including tryptophan) compared to the CF infants. Energetic efficiency was 14.0% (95% CI: 8.3%, 19.7%), 13.0% (95% CI: 6.0%, 20.0%), and 18.1% (95% CI: 9.4%, 26.8%) higher for weight, length, and head circumference, respectively, in SF infants compared to the CF infants. SF infants had significantly fewer spit-ups and softer stool consistency than CF infants.Conclusions:The SF resulted in improved parent-reported gastrointestinal tolerance and more efficient growth with less daily formula and protein intake supporting that this novel formula may potentially reduce the metabolic burden of protein overfeeding associated with infant formula.

Consumption of Different Egg-Based Diets Minimally, yet Differentially, Impacts Markers Insulin Resistance in Young Healthy Adults

ObjectivesPrevious epidemiological studies have reported conflicting associations between egg consumption and type 2 diabetes mellitus (T2DM) risk. However, many observational, survey-based studies do not fully characterize intake of additional egg-based foods or clearly differentiate between type of egg consumed. Thus, we investigated whether daily intake of whole eggs, egg whites, or an egg-free diet differentially altered markers of T2DM risk in young healthy adults. MethodsYoung, healthy men and women (18–35 y, BMI < 30 kg/m2 or <30% body fat for men and < 40% body fat for women, n = 26) participated in a randomized, crossover intervention trial where they followed an egg-free diet for 4 weeks, then were randomized to consume either 3 whole eggs or 3 egg whites per day for 4 weeks. Participants then followed a 4-week egg-free diet washout period, before switching to the alternative whole egg or egg white diet treatment. Additional egg-based foods were restricted. Fasting serum samples were collected at the end of each diet period to measure markers of T2DM risk. ResultsAverage fasting serum glucose was 90.7 mg/dL at baseline, and did not significantly change between the egg-free, egg white, or whole egg diet periods. Similarly, there were no changes in pro-inflammatory N-acetylglucosamine/galactosamine (GlycA), which is an independent predictor of insulin resistance (IR). Serum amino acids levels were further assessed, as elevated branched-chain amino acids and reduced glycine levels are predictors of prediabetes, IR, and future T2DM. Interestingly, isoleucine levels were increased following the egg white and whole egg diet as compared to the egg-free diet, whereas glycine levels were increased in by the whole egg diet only. Despite these differences, lipoprotein IR index (LP-IR) scores, which take into account NMR lipoprotein particle profiles, and diabetes risk index scores, which are calculated from LP-IR and branched-chain amino acid measures, did not change over the course of the intervention. ConclusionsOur findings indicate that eggs minimally impact IR markers in young healthy adults, with egg whites yielding more adverse changes than whole eggs. Funding SourcesThis study was funded by an Agriculture and Food Research Initiative Grant from the USDA National Institute of Food and Agriculture.

Antagonization of Ghrelin Suppresses Muscle Protein Deposition by Altering Gut Microbiota and Serum Amino Acid Composition in a Pig Model

Simple SummaryThis study investigated the effects of the antagonization of ghrelin on muscle protein deposition, eating patterns and gut microbiota in pigs by injecting ghrelin antagonist ([D-Lys3]-GHRP-6) in a short term. We found that the antagonization of ghrelin affected the eating patterns of animals, which resulted in changes in the absorption of amino acids and gut microbiota, and it reduced protein deposition in muscles. We emphasize the important role of ghrelin in promoting muscle protein deposition and provide new clues for future research on improving muscle loss.Ghrelin is an appetite-stimulating hormone that can increase food intake and has been reported to prevent muscle loss; however, the mechanism is not yet fully understood. In this study, [D-Lys3]-GHRP-6 (GHRP) was used to investigate the effects of the antagonization of ghrelin on muscle protein deposition, eating patterns and gut microbiota in a pig model. We found that the growth performance and muscle fiber cross-sectional area of pigs treated with GHRP were significantly reduced compared with the control (CON) group. Moreover, the levels of serum isoleucine, methionine, arginine and tyrosine in the GHRP group were lower than that of the CON group. The abundance of acetate-producing bacteria (Oscillospiraceae UCG-005, Parabacteroides and Oscillospiraceae NK4A214 group) and acetate concentration in the colons of pigs treated with GHRP were significantly reduced. In addition, the injection of GHRP down-regulated the mRNA expression of MCT-1 and mTOR, and it up-regulated the mRNA expression of HDAC1, FOXO1 and Beclin-1. In summary, the antagonization of ghrelin reduced the concentration of important signal molecules (Arg, Met and Ile) that activate the mTOR pathway, concurrently reduce the concentration of HDAC inhibitors (acetate), promote autophagy and finally reduce protein deposition in muscles.

The Dietary Branched-Chain Amino Acids Transition and Risk of Type 2 Diabetes Among Chinese Adults From 1997 to 2015: Based on Seven Cross-Sectional Studies and a Prospective Cohort Study.

BackgroundThe situation is grim for the prevention and control of type 2 diabetes (T2D) and prediabetes in China. Serum and dietary branched-chain amino acids (BCAAs) were risk factors for T2D. However, there is a lack of information on trends in consumption of BCAAs and the risk of T2D associated with BCAAs intake, based on nationally representative data in China. Thus, we aimed to comprehensively describe the dietary BCAAs transition and risk of T2D, at a national level among Chinese adults from 1997 to 2015.MethodsThe data sources were the China Health and Nutrition Survey (CHNS) and China Nutrition and Health Survey (CNHS). Cross-sectional data on intake were obtained from CHNS (1997, n = 9,404), CHNS (2000, n = 10,291), CHNS (2004, n = 9,682), CHNS (2006, n = 9,553), CHNS (2009, n = 9,811), CHNS (2011, n = 12,686) and CNHS (2015, n = 71,695). Prospective cohort data were obtained CHNS (1997–2015, n = 15,508).ResultsFrom 1997 to 2015, there was a significant decreasing trend in the BCAAs intake of Chinese adults in all subgroups (P < 0.0001) except for Leu in 80 or older, and a decreasing trend in the consumption of BCAAs after 40 years old (P < 0.05). The mean intake of BCAAs in the population of cohort study was 11.83 ± 3.77g/day. The 95% CI was above the HR of 1.0, when the consumptions were higher than 14.01, 3.75, 6.07, 4.21 g/day in BCAAs, Ile, Leu and Val, based on RCS curves. According to the Cox proportional hazards models, Compared with individuals with BCAAs consumption of 10.65–12.37 g/day, the multivariable-adjusted HR for diabetes was 2.26 (95% CI 1.45 to 3.51) for individuals with consumption of BCAAs more than 18.52 g/day. A statistically significant positive association between BCAAs intake and risk of T2D was observed in males or participants aged 45 years and older, but not in females or participants younger than 45 years.ConclusionOur results reveal a trend toward decreased BCAAs intake in Chinese from 1997 to 2015. After 40 years of age, consumption of BCAAs declined with increasing age. Higher BCAAs intake was associated with higher risk of T2D. This relationship is more stable among men and middle-aged and elderly people.

Serum Microelements, Amino Acids and Acyl Carnitines Levels in Pregnancies Complicated with Preeclampsia: A Prospective Study

Background: To evaluate the feasibility of serum microelements, amino acids and acyl carnitine levels to predict maternal complications and adverse infant outcomes in pregnancies complicated by preeclampsia. Methods: We launched a prospective study including 81 pregnant patients. Serum microelements, amino acids and acyl carnitine levels were tested using external calibration technique or high-performance liquid chromatography tandem mass spectrometry. Concentrations of metabolites were compared between the preeclampsia and control groups. Logistic regression models were used to assess the relevance between the metabolites and pregnancy outcomes in preeclampsia patients without severe features. Results: Concentrations of some microelements, amino acids and acyl carnitines were significantly higher or lower in preeclampsia patients. Women with severe preeclampsia had significantly lower (hexadecanoyl carnitine + octadecenoyl carnitine)/acetyl carnitine [(C16 + C18:1)/C2] compared to mothers without severe features. Lower (C16 + C18:1)/C2 was found in women who developed maternal complications (p = 0.07) or experienced adverse infant outcomes (p &lt; 0.01) compared with those who did not in patients without severe features. Levels of (C16 + C18:1)/C2 at enrollment resulted in moderate prediction rates for maternal outcomes [areas under the curves (AUC) 0.746, 95% Confidence Interval (CI) 0.543, 0.948] and perinatal outcomes (AUC 0.871, 95% CI 0.729, 1.000). Conclusions: Maternal levels of microelements, amino acids and acyl carnitines were associated with preeclampsia. Levels of (C16 + C18:1)/C2 seemed to be a potential biomarker in the prediction of maternal complications and adverse infant outcomes in preeclampsia patients without severe features. Further studies are needed to validate its predictive application.

Effects of Lysine-Lysine Dipeptide on Serum Amino Acid Profiles, Intestinal Morphology, and Microbiome in Suckling Piglets.

AimsSmall peptides are more energy-saving and efficiently absorbed compared to amino acids. Our study aimed to evaluate the effect of the Lys-Lys dipeptide on the improvement of growth performance, amino acid metabolism, and gut development in suckling piglets.Methods and ResultsTwenty-eight newborn suckling piglets were orally administrated with 0.1%, 1%, and 5% Lys-Lys dipeptide for 21 days. Our results showed that the Lys-Lys dipeptide has no significant effect on growth performance and intestinal morphology compared with the control group. We also found that the 1% Lys-Lys dipeptide significantly increased the concentrations of serum Lys, Thr, Phe, and Pro while decreasing Cys compared to the control group. Similarly, the 5% Lys-Lys dipeptide markedly increased the concentrations of serum Lys, Iso, Thr, Asp, Glu, and Pro compared to the control group. Moreover, the Lys-Lys dipeptide downregulated the expression of jejunal Slc7a1, Slc7a2, and Slc15a1 and ileal Slc7a2. Additionally, the Lys-Lys dipeptide decreased the microbiota richness indices and relative abundance of Bacteroidales.ConclusionIn this study, we found that the Lys-Lys dipeptide contributes to the metabolism of amino acids but failed to affect the growth performance of piglets. Additionally, the Lys-Lys dipeptide decreased the relative abundance of Bacteroidales. These results provide a theoretical for the future application and research of Lys-Lys dipeptide in intestinal development of suckling piglets.

Zengye Decoction Attenuated Severe Acute Pancreatitis Complicated with Acute Kidney Injury by Modulating the Gut Microbiome and Serum Amino Acid Metabolome

Objective To explore the effect and underlying mechanism of Zengye decoction (ZYD), a traditional formula from China, on the severe acute pancreatitis (SAP) rat model with acute kidney injury (AKI). Methods The SAP-AKI model was induced by 3.5% sodium taurocholate. Rats were treated with normal saline or ZYD twice and sacrificed at 36 h after modeling. Amylase, lipase, creatinine, blood urea nitrogen, kidney injury molecule 1(KIM-1), and multiple organs' pathological examinations were used to assess the protective effect of ZYD. Gut microbiome detected by 16S rRNA sequencing analysis and serum amino acid metabolome analyzed by liquid chromatography-mass spectrometry explained the underlying mechanism. The Spearman correlation analysis presented the relationship between microflora and metabolites. Results ZYD significantly decreased KIM-1(P < 0.05) and the pathological score of the pancreas (P < 0.05), colon (P < 0.05), and kidney (P < 0.05). Meanwhile, ZYD shifted the overall gut microbial structure (β-diversity, ANOSIM R = 0.14, P=0.025) and altered the microbial compositions. Notably, ZYD reduced the potentially pathogenic bacteria—Bacteroidetes, Clostridiales vadin BB60 group, and uncultured_Clostridiales_bacterium, but promoted the short-chain fatty acid (SCFA) producers—Erysipelotrichaceae, Bifidobacterium, Lactobacillus, and Moryella (all P < 0.05). Moreover, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and hierarchical clustering analysis (HCA) presented a remarkable change in amino acid metabolome after SAP-AKI induction and an apparent regulation by ZYD treatment (R2Y 0.878, P=0.01; Q2 0.531, P=0.01). Spearman's correlation analysis suggested that gut bacteria likely influenced serum metabolites levels (absolute r > 0.4 and FDR P < 0.02). Conclusions ZYD attenuated SAP-AKI by modulating the gut microbiome and serum amino acid metabolome, which may be a promising adjuvant treatment.

Effect of fecal microbiota transplantation on type 1 diabetes mellitus in non-obese diabetic mice and its underlying mechanism

Objective: To investigate the effects of fecal microbiota transplantation (FMT) on non-obese diabetic (NOD) mice of type 1 diabetes mellitus (T1DM) and its underlying mechanisms. Methods: A total of 8-9 week-female NOD mice were randomly divided into control (n=36) and FMT groups (n=36) according to the random number table. Fecal microbiota from C57BL/6 mice were transplanted into FMT group, and control group were transplanted with microbiota from themselves, once every two days for 5 times. The insulitis score and incidence of T1DM were compared between two groups;16S rRNA gene sequencing was used to evaluate the structure of fecal bacteria in NOD mice. The expressions of intestinal barrier related genes were detected by real-time quantitative PCR. The proportions of regulatory T cells (Tregs), helper T cell (Th)-1 and Th17 in the enteric-pancreatic immune axis were detected by flow cytometry. Amino acid in serum was measured by amino acid metabolomics. Results: Incidence of T1DM in NOD mice from FMT group was 40.9% (9/22), lower than 72.7% (13/22) from control group at 26 weeks of age (P=0.034). FMT promoted colonization of probiotics such as Lactobacillus, Clostridium_sp_ND2, Candidatus_Arthromitus and Clostridiaceae_1; mRNA of intestinal barrier related genes were up-regulated in FMT group [ mucins(Muc)-1: 0.93±0.29 vs 2.97±0.79, P=0.036; Muc2: 0.72±0.39 vs 10.70±3.54, P=0.019;Muc3: 1.79±0.69 vs 10.97±2.78, P=0.009;Muc4: 1.01±0.23 vs 2.42±0.49, P=0.029;Occludin(Ocln): 0.96±0.08 vs 1.81±0.36, P=0.045; Claudin(Cldn)-1:0.94±0.17 vs 2.20±0.43, P=0.022] compared to control. The proportions of Treg in mesenteric lymphoid node, pancreatic lymph node and peyer's patches of FMT group [(6.10±0.49)% vs (7.54±0.27)%, P=0.020;(5.28±0.39)% vs (6.42±0.34)%, P=0.048;(6.78±0.42)% vs (7.88±0.13)%, P=0.029] were increased compared to control,while proportions of Th1 [(1.02±0.06)% vs (0.83±0.06)%, P=0.040;(0.82±0.10)% vs (0.56±0.05)%, P=0.038;(1.28±0.12) vs (0.85±0.07), P=0.012] and proportions of Th17 [(0.40±0.01)% vs (0.30±0.02)%, P=0.004;(0.40±0.02)% vs (0.31±0.02)%, P=0.008;(0.51±0.06) vs (0.36±0.02), P=0.027] were decreased. The contents of leucine [(92.86±7.32) vs (91.87±12.62) μmol/L, P=0.027], valine [(162.74±15.97) vs (155.89±25.70) μmol/L, P=0.046] and isoleucine [(75.65±5.59) vs (73.61±9.67) μmol/L, P=0.048] in serum were decreased in FMT group. Conclusions: FMT can alleviate insulitis and T1DM occurrence in NOD mice, of which mechanism may be related to remodeling gut microbiota and improving intestinal barrier function, affecting immune response of enteric-pancreatic immune axis, correcting amino acid metabolism disorder and reducing the accumulation of branch chain amino acids in NOD mice.

Starch acylation of different short-chain fatty acids and its corresponding influence on gut microbiome and diabetic indexes

This study investigated correlations between gut microbiota and type 2 diabetic (T2D) indexes using either native resistant starch (RS, from high amylose maize starch, HAMS) or acylated starch via short-chain fatty acids (SCFAs) acylation. Compared to HAMS, consumption of acylated starch achieved a greater impact on the improvement of T2D indexes in term of body weight loss, fasting blood glucose, serum insulin level and amino acid metabolism. Intervention with acylated starches alleviated metabolism disorders and modified the gut microbiota. This study found all the acylated starch significantly enhanced the growth of SCFAs-producing bacteria compared to its native HAMS, and this change was highly consistent with their corresponding SCFAs concentration both in serum and fecal samples. This is the first reported to reveal that propionylated HAMS promoted the abundance of Bifidobacterium, while acetylated and butylated HAMS benefited the enrichment of Coprococcus, Butyricimonas and Blautia, which may indicate their different intervention pathway.

Serum Amino Acid Profiles Predict the Development of Hepatocellular Carcinoma in Patients with Chronic HBV Infection.

Background: The study aimed to find out the alterations in serum amino acid (AA) profiles and to detect their relationship with carcinoma formation. Methods: Targeted metabolomics based on ultraperformance liquid chromatography triple quadrupole mass spectrometry to quantitatively analyze serum AA levels in 136 hepatitis B (CHB) patients and 93 hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. Results: It was shown that decreased serum levels of leucine, lysine, threonine, tryptophan, valine, serotonin, and taurine were observed in more HCC patients than CHB patients, but the serum phenylalanine level was increased. Serum valine and serotonin were lower in Class C than Class A and Class B in HCC patients. Accompanied with the higher score of Model for End-Stage Liver Disease, serum phenylalanine was increased not only in CHB patients but also in HCC patients. The serum level of phenylalanine increased in the decompensated stage more than in the compensated stage, while serum leucine and serotonin significantly decreased. Serum serotonin still had significant differences between CHB and HCC both in the HBV desoxyribonucleic acid (HBV-DNA) negative group and in the HBV-DNA positive group. Furthermore, it was shown that the tryptophan ratio, branched-chain amino acids (BCAA)/aromatic amino acids ratio, BCAAs/tyrosine ratio, Fischer’s ratio, and serotonin-to-tryptophan ratio significantly decreased, while the tyrosine ratio and the kynurenine-to-tryptophan ratio increased in HCC patients more than those in CHB. Conclusions: A distinct metabolite signature of some specific serum amino acids was found between CHB and HCC patients, which may help predict the development of HCC at an early stage.