Shifts In Metabolome Research Articles

Inflammation, Gut Microbiota, and Metabolomic Shifts in Colorectal Cancer: Insights from Human and Mouse Models

Inflammation, Gut Microbiota, and Metabolomic Shifts in Colorectal Cancer: Insights from Human and Mouse Models

Metabolomic changes in preterminal serum samples of rhesus macaques exposed to two different lethal doses of total-body gamma-radiation

Exposure to ionizing radiation induces cellular and molecular damage leading to a cascade of events resulting in tissue and organ injury. Our study strives to characterize and validate metabolomic changes in preterminal stage (immediately prior to death) samples collected from rhesus macaques lethally irradiated with one of two different doses of radiation. Peripheral blood samples were collected pre-exposure, post-exposure, and at the preterminal stage of nonhuman primates (NHPs that did not survive exposure with 7.2 Gy or 7.6 Gy total-body radiation (LD60-80/60)). We analyzed global metabolomic alterations using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in serum samples collected at various timepoints in relation to radiation exposure. The goal of this study was to validate the metabolic shifts present in samples collected just prior to death, which were reported earlier in a preliminary study with a limited number of samples and a single dose of radiation. Here, we demonstrate that radiation exposure induced significant time-dependent metabolic alterations compared with pre-exposure samples. We observed significant metabolite dysregulation in animals exposed to 7.6 Gy compared to 7.2 Gy. Greater metabolic disruption was observed in the preterminal groups than all of the other post-irradiation timepoints in both cohorts. Metabolomic shifts in these preterminal groups also revealed consistent disturbances in sphingolipid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism pathways. Overall, the sphingolipid metabolism pathway appears to be representative of the preterminal phenotype, confirming the results of our preliminary study. These results offer important and novel insights for identification and validation of biomarkers for lethality, and such observations would be valuable for triage during a radiological/nuclear mass casualty scenario.

Metabolomic analysis reveals the potential of fucosylated chondroitin sulfate from sea cucumber in modulating metabolic homeostasis

In this study, we prepared four derivatives of fucosylated chondroitin sulfate (FCS): full-length FCS (flFCS) from Holothuria leucospilota, low molecular weight FCS (lmFCS) derived from flFCS, and their de-branched counterparts, de-branched flFCS (d-flFCS) and de-branched lmFCS (d-lmFCS) via controlled acid treatment. Following structural verification using various analytical techniques, we applied targeted metabolomics to examine the impact of FCS on nutritional efficacy and its structure-activity relationship. Analysis of 225 plasma and feces samples from 75 mice revealed a positive correlation between metabolomic shifts and increased weight gain, underscoring FCS’s potential to enhance nutrient absorption and promote growth. The observed linear relationship between the levels of short-chain fatty acids in plasma and feces suggests that FCS may facilitate catabolic activities in the gastrointestinal tract. The comparative study of different FCS derivatives on mouse growth and metabolic homeostasis regulation led to the conclusion that FCS exhibits greater biological activity with a higher degree of branching and larger molecular weight.

Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.

Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown. 1) To comprehensively examine gut microbiome and metabolome changes after laparoscopic vertical sleeve gastrectomy (VSG) in adolescents and 2) to assess whether the microbiome/metabolome changes observed with VSG influence phenotype using germ-free murine models. 1) A longitudinal observational study in adolescents undergoing VSG with serial stool samples undergoing shotgun metagenomic microbiome sequencing and metabolomics (polar metabolites, bile acids and short chain fatty acids) and 2) a human-to-mouse fecal transplant study. We show adolescents exhibit significant gut microbiome and metabolome shifts several months after VSG, with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited an inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG. We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.

Dual Transcriptomic and Metabolomic Analysis of Elicited Flax Sheds Light on the Kinetics of Immune Defense Activation Against the Biotrophic Pathogen Oidium lini.

Flax (Linum usitatissimum) grown under controlled conditions displayed genotype-dependent resistance to powdery mildew (Oidium lini) following COS-OGA (comprising chitosan- and pectin-derived oligomers) elicitor application. The present study reveals a two-step immune response in plants preventively challenged with the elicitor: an initial, rapid response characterized by the transcription of defense genes whose protein products act in contact with or within the cell wall, where biotrophic pathogens initially thrive, followed by a prolonged activation of cell wall peroxidases and accumulation of secondary metabolites. Thus, dozens of genes encoding membrane receptors, pathogenesis-related proteins, and wall peroxidases were initially overexpressed. Repeated COS-OGA treatments had a transient effect on the transcriptome response while cumulatively remodeling the metabolome over time, with a minimum of two applications required for maximal metabolomic shifts. Secondary metabolites, in particular terpenoids and phenylpropanoids, emerged as major components of this secondary defense response alongside pathogenesis-related proteins and wall peroxidases. The sustained accumulation of secondary metabolites, even after cessation of elicitation, contrasted with the short-lived transcriptomic response. Wall peroxidase enzyme activity also exhibited cumulative effects, increasing strongly for weeks after a third elicitor treatment. This underscores the plasticity of the plant immune response in the face of a potential infection, and the need for repeated preventive applications to achieve the full protective potential of the elicitor.

Fast Targeted Metabolomics for Analyzing Metabolic Diversity of Bacterial Indole Derivatives in ME/CFS Gut Microbiome.

Disruptions in microbial metabolite interactions due to gut microbiome dysbiosis and metabolomic shifts may contribute to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and other immune-related conditions. The aryl hydrocarbon receptor (AhR), activated upon binding various tryptophan metabolites, modulates host immune responses. This study investigates whether the metabolic diversity-the concentration distribution-of bacterial indole pathway metabolites can differentiate bacterial strains and classify ME/CFS samples. A fast targeted liquid chromatography-parallel reaction monitoring method at a rate of 4 minutes per sample was developed for large-scale analysis. This method revealed significant metabolic differences in indole derivatives among B. uniformis strains cultured from human isolates. Principal component analysis identified two major components (PC1, 68.9%; PC2, 18.7%), accounting for 87.6% of the variance and distinguishing two distinct B. uniformis clusters. The metabolic difference between clusters was particularly evident in the relative contributions of indole-3-acrylate and indole-3-aldehyde. We further measured concentration distributions of indole derivatives in ME/CFS by analyzing fecal samples from 10 patients and 10 healthy controls using the fast targeted metabolomics method. An AdaBoost-LOOCV model achieved moderate classification success with a mean LOOCV accuracy of 0.65 (Control: precision of 0.67, recall of 0.60, F1-score of 0.63; ME/CFS: precision of 0.64, recall of 0.7000, F1-score of 0.67). These results suggest that the metabolic diversity of indole derivatives from tryptophan degradation, facilitated by the fast targeted metabolomics and machine learning, is a potential biomarker for differentiating bacterial strains and classifying ME/CFS samples. Mass spectrometry datasets are accessible at the National Metabolomics Data Repository (ST002308, DOI: 10.21228/M8G13Q; ST003344, DOI: 10.21228/M8RJ9N; ST003346, DOI: 10.21228/M8RJ9N).

Identifying critical age and gender-based metabolomic shifts in a Japanese population of the Tohoku Medical Megabank cohort

Understanding the physiological changes associated with aging and the associated disease risks is essential to establish biomarkers as indicators of biological aging. This study used the NMR-measured plasma metabolome to calculate age-specific metabolite indices. In doing so, the scope of the study was deliberately simplified to capture general trends and insights into age-related changes in metabolic patterns. In addition, changes in metabolite concentrations with age were examined in detail, with the period from 55–59 to 60–64 years being a period of significant metabolic change, particularly in men, and from 45–49 to 50–54 years in females. These results illustrate the different variations in metabolite concentrations by sex and provide new insights into the relationship between age and metabolic diseases.

The dosage- and size-dependent effects of micro- and nanoplastics in lettuce roots and leaves at the growth, photosynthetic, and metabolomics levels

The occurrence of microplastics (MPs) and nanoplastics (NPs) in soils potentially induce morphological, physiological, and biochemical alterations in plants. The present study investigated the effects of MPs/NPs on lettuce (Lactuca sativa L. var. capitata) plants by focusing on (i) four different particle sizes of polyethylene micro- and nanoplastics, at (ii) four concentrations. Photosynthetic activity, morphological changes in plants, and metabolomic shifts in roots and leaves were investigated.Our findings revealed that particle size plays a pivotal role in influencing various growth traits of lettuce (biomass, color segmentation, greening index, leaf area, and photosynthetic activity), physiological parameters (including maximum quantum yield - Fv/Fmmax, or quantum yield in the steady-state Fv/FmLss, NPQLss, RfdLss, FtLss, FqLss), and metabolomic signatures. Smaller plastic sizes demonstrated a dose-dependent impact on aboveground plant structures, resulting in an overall elicitation of biosynthetic processes. Conversely, larger plastic size had a major impact on root metabolomics, leading to a negative modulation of biosynthetic processes. Specifically, the biosynthesis of secondary metabolites, phytohormone crosstalk, and the metabolism of lipids and fatty acids were among the most affected processes. In addition, nitrogen-containing compounds accumulated following plastic treatments.Our results highlighted a tight correlation between the qPCR analysis of genes associated with the soil nitrogen cycle (such as NifH, NirK, and NosZ), available nitrogen pools in soil (including NO3− and NH4), N-containing metabolites and morpho-physiological parameters of lettuce plants subjected to MPs/NPs. These findings underscore the intricate relationship between specific plastic contaminations, nitrogen dynamics, and plant performance.

Machine learning of cellular metabolic rewiring.

Metabolic rewiring allows cells to adapt their metabolism in response to evolving environmental conditions. Traditional metabolomics techniques, whether targeted or untargeted, often struggle to interpret these adaptive shifts. Here, we introduce MetaboLiteLearner, a lightweight machine learning framework that harnesses the detailed fragmentation patterns from electron ionization (EI) collected in scan mode during gas chromatography/mass spectrometry to predict changes in the metabolite composition of metabolically adapted cells. When tested on breast cancer cells with different preferences to metastasize to specific organs, MetaboLiteLearner predicted the impact of metabolic rewiring on metabolites withheld from the training dataset using only the EI spectra, without metabolite identification or pre-existing knowledge of metabolic networks. Despite its simplicity, the model learned captured shared and unique metabolomic shifts between brain- and lung-homing metastatic lineages, suggesting cellular adaptations associated with metastasis to specific organs. Integrating machine learning and metabolomics paves the way for new insights into complex cellular adaptations.

The metabolic fingerprint of chronic hepatitis C progression: Metabolome shifts and cutting-edge diagnostic options.

Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3-HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine-were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection >1 and p < 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms.

Integrative analysis of microbiota and metabolomics in chromium-exposed silkworm (Bombyx mori) midguts based on 16S rDNA sequencing and LC/MS metabolomics.

The gut microbiota, a complex ecosystem integral to host wellbeing, is modulated by environmental triggers, including exposure to heavy metals such as chromium. This study aims to comprehensively explore chromium-induced gut microbiota and metabolomic shifts in the quintessential lepidopteran model organism, the silkworm (Bombyx mori). The research deployed 16S rDNA sequence analysis and LC/MS metabolomics in its experimental design, encompassing a control group alongside low (12 g/kg) and high (24 g/kg) feeding chromium dosing regimens. Considerable heterogeneity in microbial diversity resulted between groups. Weissella emerged as potentially resilient to chromium stress, while elevated Propionibacterium was noted in the high chromium treatment group. Differential analysis tools LEfSe and random forest estimation identified key species like like Cupriavidus and unspecified Myxococcales, offering potential avenues for bioremediation. An examination of gut functionality revealed alterations in the KEGG pathways correlated with biosynthesis and degradation, suggesting an adaptive metabolic response to chromium-mediated stress. Further results indicated consequential fallout in the context of metabolomic alterations. These included an uptick in histidine and dihydropyrimidine levels under moderate-dose exposure and a surge of gentisic acid with high-dose chromium exposure. These are critical players in diverse biological processes ranging from energy metabolism and stress response to immune regulation and antioxidative mechanisms. Correlative analyses between bacterial abundance and metabolites mapped noteworthy relationships between marker bacterial species, such as Weissella and Pelomonas, and specific metabolites, emphasizing their roles in enzyme regulation, synaptic processes, and lipid metabolism. Probiotic bacteria showed robust correlations with metabolites implicated in stress response, lipid metabolism, and antioxidant processes. Our study reaffirms the intricate ties between gut microbiota and metabolite profiles and decodes some systemic adaptations under heavy-metal stress. It provides valuable insights into ecological and toxicological aspects of chromium exposure that can potentially influence silkworm resilience.

Effect of providing citrus pulp-integrated diet on fecal microbiota and serum and fecal metabolome shifts in crossbred pigs

The study aimed to assess the impact of dehydrated citrus pulp (DCP) on growth performance, fecal characteristics, fecal bacterial composition (based on 16S rRNA analysis), and fecal and serum metabolomic profiles in crossbred pigs. 80 finishing pigs Duroc × (Landrace × Large White) were fed either a control diet (C) or a diet with 240 g/kg DCP (T) for six weeks. Including DCP in diets tended to decrease feed intake, increased (p < 0.05) the concentrations of acetic and heptanoic acids and decreased (p < 0.05) fecal butyric and branched-chain fatty acid concentrations in feces. Animals fed DCP exhibited a lower abundance of the genera Clostridium and Romboutsia, while Lachnospira significantly increased. Orthogonal partial least squares discriminant analysis plotted a clear separation of fecal and serum metabolites between groups. The main discriminant fecal metabolites were associated with bacterial protein fermentation and were downregulated in T-fed pigs. In serum, DCP supplementation upregulated metabolites related to protein and fatty acids metabolism. In conclusion, the addition of DCP as an environmentally friendly source of nutrients in pig diets, resulted in modifications of fecal bacterial composition, fermentation patterns, and overall pig metabolism, suggesting improvements in protein metabolism and gut health.

Metabolic impact of polyphenol-rich aronia fruit juice mediated by inflammation status of gut microbiome donors in humanized mouse model.

The Aronia melanocarpa fruit is emerging as a health food owing to its high polyphenolic content and associated antioxidant activity. Antioxidant-rich foods, such as Aronia fruit, may counter inflammatory stimuli and positively modulate the gut microbiome. However, a comprehensive study characterizing the impact of Aronia fruit supplementation has not been completed. Therefore, we completed analyses measuring the metabolic, microbial, and inflammatory effects of a diet supplemented with Aronia fruit juice. Humanized mice were generated by colonizing gnotobiotic mice with microbiomes from human donors presenting disparate inflammation levels. Blood and fecal samples were collected throughout the course of an 8-week dietary intervention with either Aronia juice or a carbohydrate-matched beverage alone (2 weeks) or in combination with a high-fat diet to induce inflammation (6 weeks). Samples were analyzed using 16S rRNA gene sequencing (stool) and liquid chromatography-mass spectrometry (serum). We demonstrated transfer of microbiome composition and diversity and metabolic characteristics from humans with low and high inflammation levels to second-generation humanized mice. Aronia supplementation provided robust protection against high-fat diet induced metabolic and microbiome changes that were dependent in part on microbiome donor. Aronia induced increases in bacteria of the Eggerthellaceae genus (7-fold) which aligns with its known ability to metabolize (poly)phenols and in phosphatidylcholine metabolites which are consistent with improved gut barrier function. The gut microbiome from a low inflammation phenotype donor provided protection against high-fat diet induced loss of microbiome β-diversity and global metabolomic shifts compared to that from the high inflammation donor. These metabolic changes elucidate pathway-specific drivers of reduced inflammation stemming from both Aronia and the gut microbiota.

Environmental factors induced metabolome shifts during Laobaigan-flavor Baijiu fermentation

Environmental factors are the key factors affecting the fermentation of traditional fermented foods. However, the effects of environmental factors on flavor metabolism of Laobaigan-flavor Baijiu have not been described. In this study, we applied HS-SPME–GC–MS and physicochemical parameters analysis to reveal the dynamic of volatile flavor compounds and environmental factors, and indicated the effects of environmental factors on the succession of volatile flavor compounds. The fermentation process was divided into three stages: alcohols (628 mg/kg) and acids reached higher in the early stage (0–8 days), while aldehydes existed more in the middle stage (10–17 days) and esters accumulated until the middle (2501 mg/kg) or later (1168 mg/kg) stages (20–29 days). Meanwhile, environmental factors changed rapidly (p < 0.05), and significantly correlated with the formation of flavor compounds at different stages. Among them, pH and protein content were significantly related to esters (|r| > 0.6) esterified by monocarboxylic acid in the middle stage, while esters (|r| > 0.7) synthesized with hydroxyl acid had significant relations with temperature and moisture in the later stage. Our study indicated the correlations between the dynamic of environmental factors and the succession of volatile flavor compounds, and it provided a potential approach to manage environmental factors to improve the fermentation of Baijiu.

Metabolome shifts triggered by chlorine sanitisation induce Escherichia coli on fresh produce into the viable but nonculturable state

Facing the increasing occurrence of “big six” Escherichia coli outbreaks linked to fresh produce, chlorine-based sanitisers are widely used for fresh produce decontamination in recent years. However, latest finding that chlorine may induce E. coli cells into a viable not nonculturable (VBNC) state is bringing a new challenge to the fresh produce industry. VBNC cells are undetectable by the plate count test, and yet they retain pathogenicity and are more antibiotic-resistant than culturable cells. As a result, their eradication is critical to ensure the safety of fresh produce. Understanding VBNC cells at the metabolic level may provide a breakthrough for their eradication. Therefore, this study was carried out to collect the VBNC pathogenic E. coli (O26:H11, O121:H19, and O157:H7) cells from chlorine-treated pea sprouts and characterise them using NMR-based metabolomics. From the globally increased metabolite contents detected in the VBNC E. coli cells as compared to the culturable cells, mechanisms underlying E. coli’s VBNC induction were elucidated. These include rendering the energy generation scheme to become more compatible with the lowered energy needs, disaggregating protein aggregates to release amino acids for osmoprotection and later resuscitation, as well as increasing cAMP content to downregulate RpoS. These identified metabolic characteristics can inspire future development of targeted measures for VBNC E. coli cell inhibition. Our methods can also be applied to other pathogens to help lower the risk of overall foodborne diseases.

Intratumor heterogeneity and cell secretome promote chemotherapy resistance and progression of colorectal cancer

The major underlying cause for the high mortality rate in colorectal cancer (CRC) relies on its drug resistance, to which intratumor heterogeneity (ITH) contributes substantially. CRC tumors have been reported to comprise heterogeneous populations of cancer cells that can be grouped into 4 consensus molecular subtypes (CMS). However, the impact of inter-cellular interaction between these cellular states on the emergence of drug resistance and CRC progression remains elusive. Here, we explored the interaction between cell lines belonging to the CMS1 (HCT116 and LoVo) and the CMS4 (SW620 and MDST8) in a 3D coculture model, mimicking the ITH of CRC. The spatial distribution of each cell population showed that CMS1 cells had a preference to grow in the center of cocultured spheroids, while CMS4 cells localized at the periphery, in line with observations in tumors from CRC patients. Cocultures of CMS1 and CMS4 cells did not alter cell growth, but significantly sustained the survival of both CMS1 and CMS4 cells in response to the front-line chemotherapeutic agent 5-fluorouracil (5-FU). Mechanistically, the secretome of CMS1 cells exhibited a remarkable protective effect for CMS4 cells against 5-FU treatment, while promoting cellular invasion. Secreted metabolites may be responsible for these effects, as demonstrated by the existence of 5-FU induced metabolomic shifts, as well as by the experimental transfer of the metabolome between CMS1 and CMS4 cells. Overall, our results suggest that the interplay between CMS1 and CMS4 cells stimulates CRC progression and reduces the efficacy of chemotherapy.

Abstract LB348: A controlled high fiber dietary intervention alters metabolome and gut microbiome in melanoma survivors

Abstract Background: Multiple studies support the gut microbiome as playing a key role in response to immune checkpoint blockade (ICB). Habitual dietary fiber intake has been associated with improved response to ICB. We conducted a pilot feasibility study of a high-fiber dietary intervention (HFDI) in melanoma survivors. Methods: Melanoma survivors (BMI &amp;lt;40 kg/m2, currently not on active therapy) were enrolled to a 6-week controlled feeding study in which all meals were provided by MD Anderson Cancer Center Bionutrition Research Core. Target daily fiber intake was up to 50 g/day derived from whole foods. The primary outcome was compliance. Blood and stool were collected q 2 weeks. Whole genome shotgun sequencing (WGS) was performed on fecal specimens, and metabolomics was conducted using mass spectroscopy on blood and stool. Results: Ten participants were enrolled, of which 60% were female. Average BMI was 31.4 kg/m2, and average baseline fiber intake was 17.8 g/day (range 7.4-28.3 g/day). Overall compliance was 88% (95% CI 83%-93%) with 45.8 g/day fiber reached (range 40.0-50.0 g/day). HFDI was well-tolerated with 1 participant experiencing grade 2 diarrhea and all other AEs were grade 1: diarrhea (40%), bloating (50%), flatulence (60%) and abdominal pain (10%). Exploratory analyses of global and targeted metabolomics showed increases in the short chain fatty acid acetate, shifts in omega-3/6 PUFAs, and indole/tryptophan metabolism. Stool WGS analyses showed that the largest shifts in gut microbiome structure in those who started with the lowest baseline fiber intake. Conclusion: A HFDI is well-tolerated and feasible in a melanoma population. The expected shifts in metabolome and gut microbiome observed with HFDI support that participants were compliant. Thus, this intervention is currently being tested in a Phase II study in metastatic melanoma patients receiving ICB. Citation Format: Yan Jiang. A controlled high fiber dietary intervention alters metabolome and gut microbiome in melanoma survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB348.

Berries in Microbiome-Mediated Gastrointestinal, Metabolic, and Immune Health.

Current research has shown that berry-derived polymeric substrates that resist human digestion (dietary fibers and polyphenols) are extensively metabolized in the gastrointestinal tract dominated by microbiota. This review assesses current epidemiological, experimental, and clinical evidence of how berry (strawberry, blueberry, raspberry, blackberry, cranberry, black currant, and grapes) phytochemicals interact with the microbiome and shape health or metabolic risk factor outcomes. There is agrowing evidence that the compositional differences among complex carbohydrate fractions and classes of polyphenols define reversible shifts in microbial populations and human metabolome to promote gastrointestinal health. Interventions to prevent gastrointestinal inflammation and improve metabolic outcomes may be achieved with selection of berries that provide distinct polysaccharide substrates for selective multiplication of beneficial microbiota or oligomeric decoys for binding and elimination of the pathogens, as well as phenolic substrates that hold potential to modulate gastrointestinal mucins, reduce luminal oxygen, and release small phenolic metabolites signatures capable of ameliorating inflammatory and metabolic perturbations. These mechanisms may explain many of the differences in microbiota and host gastrointestinal responses associated with increased consumption of berries, and highlight potential opportunities to intentionally shift gut microbiome profiles or to modulate risk factors associated with better nutrition and health outcomes.

Amino acid, sugar, phenolic, and terpenoid profiles are capable of distinguishing Citrus tristeza virus infection status in citrus cultivars: Grapefruit, lemon, mandarin, and sweet orange.

Citrus tristeza virus (CTV) is the most severe viral disease for citrus production. Many strains of CTV have been characterized and their symptomology widely varies, ranging from asymptomatic or mild infections to severe symptomology that results in substantial yield loss or host death. The capacity of the different CTV strains to affect the biochemistry of different citrus species has remained largely unstudied, despite that associated metabolomic shifts would be relevant toward symptom development. Thus, amino acid, sugar, phenolic, and terpenoid levels were assessed in leaves of healthy and CTV-infected grapefruit, lemon, mandarin, and two different sweet orange cultivars. Both mild [VT-negative (VT-)] and severe [VT-positive (VT+)] CTV genotype strains were utilized. When looking at overall totals of these metabolite classes, only amino acid levels were significantly increased by infection of citrus with severe CTV strains, relative to mild CTV strains or healthy plants. No significant trends of CTV infection on summed amounts of all sugar, phenolic, or terpenoid compounds were observed. However, individual compound levels were affected by CTV infections. Subsequent canonical discriminant analysis (CDA) that utilized profiles of individual amino acids, terpenoids, or phenolics successfully distinguished leaf samples to specific citrus varieties and identified infection status with good accuracy. Collectively, this study reveals biochemical patterns associated with severity of CTV infections that can potentially be utilized to help identify in-field CTV infections of economic relevance.

Microbiome-metabolomics analysis of the effects of decreasing dietary crude protein content on goat rumen mictobiota and metabolites.

ObjectiveThe objective of this study was to investigate the effects of decreasing dietary crude protein content on rumen fermentation, mictobiota, and metabolites in goats.MethodsIn an 84-day feeding trial, a total of twelve male Anhui white goat kids with initial body weight 15.9±1.13 kg were selected and randomly classified into two groups, feeding a normal crude protein diet (14.8% CP, NCP) or a low crude protein diet (12.0% CP, LCP). At the end of the experimental trial (on day 84), six animals were randomly selected from each group and were slaughtered to collect rumen fluid samples for the analysis of rumen fermentation parameters, microbiome, and metabolome.ResultsThe concentrations of ammonia-nitrogen, total volatile fatty acid, acetate, and propionate were decreased (p<0.05) in the LCP group in comparison with those in the NCP group. The abundances of genera Prevotella, Campylobacter, Synergistetes, and TG5, which were associated with nitrogen metabolism, were lower (p<0.05) in the LCP group compared with those in the NCP group. The levels of 78 metabolites (74 decreased, 4 increased) in the rumen fluid were altered (p<0.05) by the treatment. Most of the ruminal metabolites that showed decreased levels in the LCP group were substrates for microbial protein synthesis. Metabolic pathway analysis showed that vitamin B6 metabolism was significantly different (p<0.05) in rumen fluid between the two treatments.ConclusionDecreased dietary protein level inhibited rumen fermentation through microbiome and metabolome shifts in goat kids. These results enhance our understanding of ruminal bacteria and metabolites of goat fed a low protein diet.