bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosahexaenoic Acid Improves the Decrement in Antibody Production Upon Influenza Infection of Obese Mice Through the Production of Pro‐Resolving Lipid Mediators
Authors: Guesdon William , Crouch Miranda , Kosaraju Rasagna , Armstrong Mike , Reisdorph Nichole , Shaikh Saame Raza 
Published: November 2023

Obesity is associated with an increased risk of infection and poor response to vaccination, which may be driven by impaired antibody production. Therefore, therapeutic strategies are needed to enhance the humoral response. We previously demonstrated that n‐3 polyunsaturated fatty acids (PUFA) can enhance antibody production to a T‐independent antigen. Therefore, we tested the possibility that the n‐3 PUFA docosahexaenoic acid (DHA) could improve antibody production upon influenza infection in obese mice. To investigate the effect of DHA on humoral immunity, we fed mice for 15 weeks with a control or a high fat diet with or without DHA supplementation followed by infection with influenza A/Puerto Rico/8/34. Our findings reveal that DHA supplementation improved the decrement in hemagglutination inhibition (HAI) titers of obese mice after influenza infection. Mechanistically, DHA did not target B‐cell PPARγ (peroxisome proliferator‐activated receptors) or the DHA‐sensing G‐protein coupled receptor 120 to boost antibody levels. Instead, DHA increased the levels of downstream D‐series specialized pro‐resolving lipid mediators (SPMs), which are known to increase antibody production through the generation of CD138+ antibody secreting cells. Specifically, we identified 14‐HDHA to be elevated upon DHA intervention, which elevated HAI titers upon influenza infection and increased the frequency of CD138+ cells. Overall, the results suggest that DHA may have potential therapeutic applications for improving humoral immunity.Support or Funding InformationSupported by NIH R01AT008375 (SRS).
The Leucine Metabolic Pathway is Differentially Regulated by c‐MYC and NFAT in T cells and Their Cancerous Counterpart EL‐4 lymphoma cells
Authors: Brenner Michelle , Torres Ashley , Hutson Susan , Ananieva Elitsa 
Published: November 2023

Tumor cells can escape immune surveillance by competing with T cells for common metabolites and redirecting nutrients for their own advantage. Leucine is a nutrient that stimulates protein biosynthesis, while the degradation of leucine provides energy and metabolites for the TCA cycle. The first two enzymatic steps in leucine degradation are catalyzed by the branched‐chain aminotransferase (cytosolic BCATc and mitochondrial BCATm, step 1) and the branched‐chain α‐ketoacid dehydrogenase complex (BCKDC) that is composed of three enzymes, E1, E2, and E3 (step 2). The gene regulation of these enzymes is largely unknown but important to understand how T cells and cancer cells interact on metabolic level in the tumor microenvironment. The objective of this research was to compare the gene regulation of BCATc, BCATm, the E1α subunit of E1, and E2 in T cells and their cancerous counterpart, EL‐4 lymphoma cells, and better understand the function of the leucine metabolic pathway in these cells. Bioinformatic analysis revealed that the transcription factors c‐Myc and NFAT (nuclear factor of activated T cells) have binding sites at the promoter regions of the genes encoding for BCATm, BCATc, E1α, and E2. We consequently treated activated T cells and EL‐4 lymphoma cells with 1μM cyclosporine A (CsA) and 100μM 10058‐F4, which inhibit NFAT and c‐Myc, respectively. Next, we explored the impact of CsA and NFAT treatments on the mRNA and protein expression of the BCAT and BCKDC enzymes and found that 10058‐F4 inhibited all genes in both activated T cells and EL‐4 cells. These results suggest that T cells and EL‐4 lymphoma cells use c‐Myc to up‐regulate the leucine metabolic pathway upon T cell activation and/or EL‐4 lymphoma growth. CsA, on the other hand, inhibited the protein expression of BCATc and E2 in T cells only implying that NFAT pathway activates the first two steps in leucine degradation in activated T cells but not in EL‐4 lymphoma cells. This research will aid in exploring possibilities to modulate the leucine metabolic pathway in a direction that provides an advantage to T cells to better combat cancer cells in the tumor microenvironment.Support or Funding InformationIOER startup, Des Moines University (Ananieva, EA)
Guanylate Binding Protein 1 Regulates Metabolic Reprograming and Polarization of Macrophages
Authors: Qiu Xiaoxue , Guo Hong , Chen Xiaoli 
Published: November 2023

Guanylate binding protein 1 (Gbp1) is a large GTPase that plays a critical role in regulating autophagic pathway activation in macrophages during innate immune responses to pathogen infection. Previous research has mostly focused on the anti‐microbial functions of Gbp1 in macrophages, while the role of Gbp1 in regulating nutrient metabolism and polarization of macrophages remains poorly understood. Pro‐inflammatory polarization of macrophages is an important contributor to adipose tissue inflammation and its associated insulin resistance. Defining the molecular mechanism regulating polarization and metabolic reprograming of macrophages is important to the etiology and therapeutic intervention of adipose tissue inflammation. To investigate the role of Gbp1 in macrophage metabolism and polarization, we established stable Gbp1 knockdown (Kd) Raw264 macrophage cell lines. We found that downregulation of Gbp1 causes macrophage polarization towards a more pro‐inflammatory phenotype in response to lipopolysaccharide (LPS) or interferon‐gamma (IFNγ) treatment, as demonstrated by enhanced activation of NFκB signaling pathway, increased gene expression levels of interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNFα) compared to scrambled (Scr) macrophages. Next, we assessed the mitochondrial oxidative metabolism of Scr and Gbp1 Kd macrophages treated with IFNγ or LPS. Mitochondrial respiration profiling by the Seahorse XF24 extracellular flux analyzer showed that loss of Gbp1 impairs mitochondrial respiration leading to a significant decrease in oxygen consumption rate compared to Scr macrophages in the basal and IFNγ‐treated condition. Moreover, Gbp1 Kd macrophages had significantly lower mRNA expression levels of genes encoding electron transport chain components than Scr cells, suggesting that loss of Gbp1 disrupts oxidative metabolism of macrophages. We then determined if Gbp1 downregulation affects mitophagy activity, which may contribute to mitochondrial dysfunction in Gbp1 Kd macrophages. As expected, parkin protein levels were reduced, while phosphorylated AMPK levels were increased in the mitochondrial fraction isolated from Gbp1 Kd macrophages compared to that from Scr cells. Consistently, Gbp1 deficiency causes an increase in protein levels of p62 and LC3II in the basal and IFNγ/LPS‐treated conditions in the presence and absence of BafA1, suggesting impaired autophagic‐lysosomal pathway activation in Gbp1 Kd macrophages. We conclude that Gbp1 has a beneficial role in suppressing inflammation and promoting oxidative metabolism of nutrients in macrophages via positive regulation of mitophagy activity.Support or Funding InformationNIDDK‐funded Minnesota Obesity Center (P30DK050456)
Clinical Evaluation of the Effect of a Fermentate from Yeast on Digestive Comfort, Stool Parameters and Prebiotic Modulation of the Gut Microbiota
Authors: Robinson Larry , Pinheiro Iris , Verhelst An , Sanabria Emma Hernandez , Abbeele Pieter , Possemiers Sam 
Published: November 2023

Gastrointestinal (GI) discomfort and reduced bowel movements are a common symptom in otherwise healthy individuals, affecting up to 20% of adults. EpiCor®, a specific fermentate made using Saccharomyces cerevisiae, was previously shown in vitro and in vivo to affect the gut microbiota and gut barrier. Given the link between gut function and gut microbiota, the aim of this intervention study was to investigate the effect of the fermentate on (GI) discomfort upon 6‐week daily intake by a population with mild symptoms of GI discomfort and constipation.In this randomized, double‐blind, placebo‐controlled study, 80 individuals were randomly assigned to groups receiving the fermentate from yeast (500 mg/d) or placebo (maltodextrin, 500 mg/d) for 6 wks. Effects on bowel function and GI discomfort were assessed by a combination of daily records and questionnaires recorded at baseline, after 3 weeks and at the end of the study. Additionally, effects on gut microbial community composition and activity were evaluated in stool samples collected at the same time points.Baseline analysis of symptom scores and gut microbiota profiles revealed a correlation between intensity of GI complaints and gut microbiota composition, with indications of dysbiosis in those individuals with increased GI complaints (e.g., lower levels of key bacterial taxa and increased fecal lactate levels). Analysis of the diaries and questionnaires revealed, despite an apparent placebo effect in part of the population, a significant improvement of GI symptoms (bloating/distention, feeling of fullness and total score), stool frequency and stool consistency upon repeated intake of the fermentate. Furthermore, this was associated with improved Quality of Life parameters and lower perceived stress levels. Finally, gut microbiota analysis by Illumina sequencing revealed multiple changes in microbial community composition and metabolite analysis showed a decrease in lactate levels.In conclusion, this human intervention study confirms that the fermentate is able to modulate the gut microbial community in individuals with moderate symptoms of GI discomfort and constipation. This resulted in decreased severity of GI symptoms and normalization of bowel function, which in turn resulted in improved wellbeing of the subject. These data therefore suggest a highly promising role for well‐validated ingredients in ameliorating a condition that affects a major part of the population.Support or Funding InformationFunded by Embria Health Sciences, 2105 SE Creekview Dr., Ankeny, IA 50021
PCB126 Exposure Modulates Gut Microbial Fermentation of the Dietary Fiber Inulin
Authors: Hoffman Jessie Baldwin , Flythe Michael , Hennig Bernhard 
Published: November 2023

Exposure to environmental pollutants is associated with a greater risk for metabolic diseases including cardiovascular disease. Pollutant exposure can also alter gut microbial populations that may contribute to metabolic effects and progression of inflammatory diseases. Short‐chain fatty acids (SCFAs), produced from gut microbial fermentation of dietary fibers such as inulin, exert numerous effects on host energy metabolism. SCFAs are also linked to health promoting effects, including a reduced risk of inflammatory diseases. We hypothesized that exposure to dioxin‐like pollutants modulate gut microbial fermentation processes. Fecal microbes from mice were harvested and resuspended in anaerobic media containing 4 or 10g/L of inulin with or without PCB126 (0.02μM, 0.2μM, or 2μM) and incubated for 48h (37 °C). HPLC analysis revealed that PCB126 exposure differentially modulated the production of several SCFA, including succinate and propionate. Exposure to PCB126 at 0.2μM and 2μM reduced succinate production, while exposure to 2μM of PCB126 increased total fermentation acids, and in particular propionate production. Interestingly, increasing the fiber substrate source to 10g/L abolished all effects of PCB126 on SCFA production. It has been demonstrated that bacteria‐produced succinate contributes to metabolic benefits by acting as an intestinal gluconeogenic substrate. Furthermore, there is evidence that an excess propionate and total SCFA can contribute to increased energy harvest and hepatic lipogenesis. Increased consumption of dietary fiber intake is associated with improved metabolic outcomes and gut health. Thus, this evidence supports the idea that pollutant exposure may contribute to alterations in host metabolism through gut microbiota‐dependent mechanisms, and that an increased level of dietary fiber might be able to attenuate these responses.Support or Funding InformationNIEHS/NIH grants P42ES007380NIH Training Grant T32 DK007778.
Dietary Supplementation with Raspberry Whole Fruit Modifies the Relative Abundance of Fecal Microbial Communities in Obese Diabetic (db/db) Mice
Authors: Noratto Giuliana , Garcia‐Mazcorro Jose , Chew Boon P. , Mertens‐Talcott Susanne U. 
Published: November 2023

We studied if dietary supplementation with red raspberries can modulate the fecal microbiota of db/db mice. Fecal samples from db/db mice fed a raspberry‐supplemented diet (n=12) or an isocaloric control diet (n=15) were used for microbial description using 16S rDNA sequencing with a MiSeq instrument (Illumina). Microbial taxonomy assignments were based on a curated good‐quality 16S database (GreenGenes). A total of 2.6 million good‐quality sequences (average: 272 nucleotide long) were available for taxonomic and diversity analysis. These sequences were assigned to 3,857 different groups of sequences or Operational Taxonomy Units.There were no significant treatment differences in the two more predominant phyla Firmicutes and Bacteroidetes, each comprising of many different species of bacteria. Interestingly, when looking at deeper taxonomic levels within each phylum, raspberry supplementation was associated with higher relative proportions of Lachnospiraceae, a group that has been shown to be depleted during disease processes inside the gut such as inflammatory bowel disease. Raspberry‐supplemented obese mice also showed relatively lower abundance of an interesting fiber degrader (family S24‐7). This is important to point out because the combined effects of polyphenolic compounds and fiber in raspberries have not been studied. Changes in Lachnospiraceae, S24‐7 and a few other groups adequately differentiated treatment differences in the whole microbial composition. In conclusion, consumption of raspberry is associated with changes in fecal microbial communities of db/db mice; thus future studies on the potential beneficial effect of raspberries on intestinal health are warranted.Support or Funding InformationNational Raspberry Council
The Relationship Between Abnormal Metabolic Status and the Breastmilk Microbiome in Women Three Months Post‐Partum
Authors: LeMay‐Nedjelski Lauren , Ley Sylvia H. , Hanley Anthony J. , Stintzi Alain , Butcher James , Wang Pauline W. , Copeland Julia K. , Unger Sharon , O'Connor Deborah L. 
Published: November 2023

BackgroundThe gastrointestinal (gut) microbiome established during infancy plays an important role in the maturation of the gastrointestinal tract and immune system. In addition, a growing body of evidence suggests gut microbial community composition may impact short‐ and long‐term health. Breastmilk contains a vast array of microbes and is believed to play a role in early colonization of the infant gut. Maternal metabolic status and infant mode of delivery have been suggested to influence the microbial milieu of breastmilk, however, systematic investigation of these associations is required. The objective of this study was to determine if maternal gestational diabetes mellitus (GDM), impaired glucose tolerance (IGT), or mode of delivery (scheduled caesarean delivery [C‐section], unscheduled C‐section, vaginal delivery) impacts the microbial composition of breastmilk.MethodsMetagenomic DNA extraction and 16S gene sequencing of the rDNA V4 hypervariable region was carried out on breastmilk to determine microbial composition. Breastmilk samples were obtained from complete breastmilk expressions at three months post‐partum from otherwise healthy women who delivered term‐born infants (n= 116).ResultsPrincipal coordinate analysis of Bray‐Curtis dissimilarity did not reveal clustering of the different groups (non‐GDM versus GDM; non‐GDM versus IGT versus GDM; scheduled C‐section versus unscheduled C‐section versus vaginal delivery; total C‐section versus vaginal delivery). In addition, no major differences in alpha diversity were found between the GDM status groups or delivery method groups using the Chao1 index. Proteobacteria and Firmicutes were found to be the predominant phyla in the breastmilk sample. Genus level analyses revealed high abundance of Pseudomonas and Streptococcus genera regardless of maternal metabolic status or mode of delivery. Low levels of Staphylococcus, Veillonella and Acinetobacter were also found among all of the groups.SignificanceThese findings may indicate that the microbiome of mature breastmilk at three months post‐partum may be resistant to perturbation by maternal metabolic abnormalities and mode of delivery. Thus, breastmilk may play an important role in mitigating the effects of other factors that negatively affect colonization of the infant gut. Further research in this area is warranted.Support or Funding InformationCanadian Institutes of Health Research, Canadian Diabetes Association
Human Breast Milk Microbiota is Influenced by Maternal Age and BMI, Stage of Lactation and Infant Feeding Practices
Authors: Li Chen , Gonzalez Emmanuel , Solomons Noel W , Scott Marilyn E , Koski Kristine G 
Published: November 2023

BackgroundHuman breast milk contains a diverse population of bacteria, but factors influencing the milk microbiota have not been described.ObjectiveWe explored if maternal age, BMI, stage of lactation and infant feeding practices influenced bacterial communities in breast milk of indigenous mothers in the western highlands of Guatemala.MethodsIn this cross‐sectional study, unilateral milk samples were collected from Mam‐Mayan women during early (5‐46d, n=33) or established (4‐6mo, n=43) lactation. Maternal age, BMI and feeding practices (exclusive, predominant and mixed feeding) were recorded. Milk bacterial communities were characterized by 16S ribosomal RNA amplicon sequencing using Illumina MiSeq platform. Sequence treatment, taxonomy assignment and operational taxonomic unit counts were performed with customized scripts based on Mothur and Dada2 MiSeq protocols. Taxonomy assignment was based on a >95% confidence threshold. We compared normal (BMI 18.5–24.9) vs. overweight (BMI 25–30), early vs. established lactation and exclusive/predominant breastfeeding vs. mixed feeding. For all statistical tests, an effect size >1.0, a confidence interval >95% and a p‐value and q‐value <0.05 were considered significant.ResultsHuman milk bacterial community was altered by maternal BMI, stage of lactation, infant feeding practices whereas bacterial diversity was only affected by maternal age. The highest bacterial diversity occurred in mothers aged 22–24 (Shannon index 1.8) and the lowest bacterial diversity occurred in mothers aged 13–15 (Shannon index 1). At the phylum level, stage of lactation modified the proportion of Firmicutes and Proteobacteria. Firmicutes was >20% higher in early lactation and Proteobacteria was 30% higher in established lactation. A normal BMI was associated with higher proportions of Alphaproteobacteria and Betaproteobacteria at the class level. At the family level, exclusive/predominant breastfeeding when to compared to mixed feeding was associated with higher proportions of Corynebacteriaceae, Lactobacillaceae and Rhodobacteraceae.ConclusionHuman breast milk bacterial communities are determined by a complex interplay of maternal factors, stage of lactation and infant feeding practices. Exclusive breastfeeding might be necessary for the shaping of a healthy microbiota in the nursing infant. Finally, our data demonstrate the need to better understand the factors that contribute to the establishment of human breast milk microbiota, which could in turn influence infant growth and development.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (NSERC)
In Vitro Assessment of Prebiotic Potential of Culinary Spices
Authors: Lu Qing‐Yi , Summanen Paula , Lee Ru‐Po , Huang Jianjun , Henning Susanne , Heber David , Findgold Sidney , Li Zhaoping 
Published: November 2023

BackgroundSpices are rich sources of phenolic compounds and have a number of demonstrated disease preventive activities. Diet is one of the important factors contributing to the gut microbial composition that ultimately affects human health. Several recent in vitro, in vivo and human studies showed that (poly)phenol‐rich dietary sources influence the relative abundance of different bacterial groups within the gut microbiota by reducing the numbers of potential pathogen and certain Gram‐negative Bacteroides species and enhancing beneficial bifidobacteria and lactobacilli.ObjectiveThe present study investigated chemical composition, antioxidant activity and prebiotic potential of spices using an in vitro model.MethodsSeven culinary spices including black pepper (BLP), cayenne pepper (CAP), cinnamon (CIN), ginger (GIN), Mediterranean oregano (ORE), rosemary (ROS) and turmeric (TUR) were extracted with boiling water. Major chemical constituents were characterized by UV‐HPLC method and antioxidant capacity was determined by measuring colorimetrically the extent to scavenge ABTS+ radical cations. Effects of spice extracts on the growth of 88 intestinal bacterial strains were determined by using Brucella agar plates containing serial dilutions of extracts.ResultsA total of 13 phenolic compounds, a piperine, cinnamic acid and cinnamaldehyde were identified and quantitated from 7 spices. Spice extracts exhibited high antioxidant capacity that correlated with the total amount of major chemical constituents identified. All spice extracts, with the exception of TUR, stimulated the growth of Bifidobacterium spp. and Lactobacillus spp. All spices exhibited high inhibitory activity against Ruminococcus species. CIN, ORE and ROS were active against Fusobacterium strains, and CIN, ROS and TUR were active against Clostridium spp.ConclusionsSeveral spices displayed prebiotic‐like activity by promoting the growth of beneficial bacteria and suppressing the growth of pathogenic bacteria, suggesting their potential role in the regulation of intestinal microbiota and the enhancement of gastrointestinal health. The identification and quantification of spice‐specific phytochemicals provided insight into the potential influence of these chemicals on the gut microbial communities and activities.Support or Funding InformationSupported by departmental funds from the Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles.