Pinto Beans Supplementation Impacted the Gut Microbiome, Inflammation, MHC II Expression and Glucose Homeostasis in C57BL/6 J Mice Regardless of Dietary Fat Content (P21-028-19)

Abstract Objectives Fiber-rich foods such as pinto beans (PB) may exhibit prebiotic effects by preventing early immunosuppression and gut permeability associated with the onset of insulin resistance (IR). Thus, this study evaluated the early protective effects of PB supplementation on the cecal gut microflora, tight-junction protein abundances, gut inflammatory markers and glucose homeostasis in mice fed either a control (C) or a high-fat, high sucrose (HFS). Methods Six-wk-old, male C57BL/6 J mice were randomly assigned to four groups (n = 12/group) and fed a control (C, 10% kcal fat, 10% kcal sucrose) or HFS (45% kcal fat, 20% kcal sucrose) diet with or without 10% (wt/wt) freeze-dried PB for 30 d. Measures include fasting blood glucose (FBG), cecal bacteria analyses by 16 S rDNA sequencing, gene expression of gut antimicrobial peptides and markers of inflammation in the distal ileum by qPCR, and expression of tight junction proteins, STAT3 and MHC II in the distal ileum by immunoblotting. Statistical analyses include the Kruskal-Wallis/Dunn's post-hoc test, and a 2-way ANOVA using factors of HFS and PB. Results FBG was increased by HFS (main effect, P = 0.0070) while PB decreased FBG by at least 13% (main effect, P = 0.046). In the cecum, the sulfide-producing bacteria family Desulfovibrionaceae (genus Bilophilia) was decreased (≤49%, P ≤ 0.022) in the PB-fed mice compared to their controls. In contrast, the short chain fatty acid-producing family Lachnospiraceae, was elevated by at least 47% (P ≤ 0.0043) in the PB-fed groups compared to their controls. We also observed a 3-fold decrease (P = 0.012) in Ifng gene expression in the HFS group compared to control, together with a decrease in the phosphorylation of STAT3 in the distal ileum (P = 0.045). On the other hand, PB supplementation increased pSTAT3 (main effect, P = 0.022), MHC II (≥66%, main effect, P = 0.0040), with a trend to upregulate occludin (P = 0.055). Moreover, antimicrobial peptide genes, Reg3β and Reg3γ, and Il10 were upregulated by PB (main effect, P < 0.0094). Finally, a negative correlation between the genus Bilophilia and MHC II (Spearman, ρ = −0.5747, P = 0.0033) was observed Conclusions PB supplementation modulated the gut microbiome regardless of dietary fat content, and upregulated MHC II in the distal ileum. These effects may be central to its potential to protect against diet-induced IR Funding Sources Northarvest Bean Growers Association.

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Pinto beans modulate the gut microbiome, augment MHC II protein, and antimicrobial peptide gene expression in mice fed a normal or western-style diet

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2020.108543 ◽

2021 ◽

Vol 88 ◽

pp. 108543

Author(s):

Babajide A. Ojo ◽

Peiran Lu ◽

Sanmi E. Alake ◽

Bryant Keirns ◽

Kendall Anderson ◽

...

Keyword(s):

Gene Expression ◽

Antimicrobial Peptide ◽

Gut Microbiome ◽

Mhc Ii ◽

Pinto Beans ◽

Peptide Gene

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Programming With Varying Dietary Fat Content Alters Cardiac Insulin Receptor, Glut4 and FoxO1 Immunoreactivity in Neonatal Rats, Whereas High Fat Programming Alters Cebpa Gene Expression in Neonatal Female Rats

Frontiers in Endocrinology ◽

10.3389/fendo.2021.772095 ◽

2022 ◽

Vol 12 ◽

Author(s):

Annelene Govindsamy ◽

Samira Ghoor ◽

Marlon E. Cerf

Keyword(s):

Gene Expression ◽

Insulin Receptor ◽

Insulin Signaling ◽

Dietary Fat ◽

High Fat Diet ◽

Female Offspring ◽

Fat Content ◽

Neonatal Rats ◽

Cardiac Physiology ◽

High Fat

Fetal programming refers to an intrauterine stimulus or insult that shapes growth, development and health outcomes. Dependent on the quality and quantity, dietary fats can be beneficial or detrimental for the growth of the fetus and can alter insulin signaling by regulating the expression of key factors. The effects of varying dietary fat content on the expression profiles of factors in the neonatal female and male rat heart were investigated and analyzed in control (10% fat), 20F (20% fat), 30F (30% fat) and 40F (40% fat which was a high fat diet used to induce high fat programming) neonatal rats. The whole neonatal heart was immunostained for insulin receptor, glucose transporter 4 (Glut4) and forkhead box protein 1 (FoxO1), followed by image analysis. The expression of 84 genes, commonly associated with the insulin signaling pathway, were then examined in 40F female and 40F male offspring. Maintenance on diets, varying in fat content during fetal life, altered the expression of cardiac factors, with changes induced from 20% fat in female neonates, but from 30% fat in male neonates. Further, CCAAT/enhancer-binding protein alpha (Cebpa) was upregulated in 40F female neonates. There was, however, differential expression of several insulin signaling genes in 40F (high fat programmed) offspring, with some tending to significance but most differences were in fold changes (≥1.5 fold). The increased immunoreactivity for insulin receptor, Glut4 and FoxO1 in 20F female and 30F male neonatal rats may reflect a compensatory response to programming to maintain cardiac physiology. Cebpa was upregulated in female offspring maintained on a high fat diet, with fold increases in other insulin signaling genes viz. Aebp1, Cfd (adipsin), Adra1d, Prkcg, Igfbp, Retn (resistin) and Ucp1. In female offspring maintained on a high fat diet, increased Cebpa gene expression (concomitant with fold increases in other insulin signaling genes) may reflect cardiac stress and an adaptative response to cardiac inflammation, stress and/or injury, after high fat programming. Diet and the sex are determinants of cardiac physiology and pathophysiology, reflecting divergent mechanisms that are sex-specific.

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Oligosaccharide equine feed supplement, Immulix, has minor impact on vaccine responses in mice

Scientific Reports ◽

10.1038/s41598-021-04132-8 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Ida Wang Henriksen ◽

Josue Leonardo Castro Mejia ◽

Caroline Martha Junker Mentzel ◽

Frederikke Lindenberg ◽

Axel Kornerup Hansen

Keyword(s):

Gene Expression ◽

Dietary Fat ◽

Immune Cell ◽

Mammalian Species ◽

Fat Content ◽

Male Mice ◽

Vaccine Response ◽

Biologically Relevant ◽

Vaccine Responses ◽

Tetanus Vaccine

AbstractSeveral mammalian species are vaccinated in early life, but little is known about the effect of diet on vaccine response. Oligosaccharides are increasingly proposed as dietary supplement for young individuals due to their anti-inflammatory potential elicited through modulation of gut microbiota (GM). Also, diet, e.g. the size of the fat fraction, is known to modulate the GM. We tested if an oligosaccharide diet (Immulix) and/or increased dietary fat content affected antibody titers to a tetanus vaccine in 48 BALB/cJTac mice through GM modulation. Female mice had significantly higher IgG titers with higher variation compared to male mice. The effects of Immulix and/or increased fat content were minor. Immulix negatively affected IgG titers in male mice four weeks after secondary vaccination but upregulated Il1b gene expression in the spleen. Immulix had a downregulating effect on expression of Cd4 and Foxp3 in ileum only if the mice were fed the diet with increased fat. The diet with increased dietary fat increased Il1b but decreased Cd8a gene expression in the spleen. Immulix and diet affected GM composition significantly. Increased dietary fat content upregulated Lactobacillus animalis but downregulated an unclassified Prevotella spp. Immulix decreased Lactobacillales, Streptococcaceae and Prevotellaceae but increased Bacteroides. It is concluded that in spite of some minor influences on immune cell markers, cytokines and IgG titers Immulix feeding or increased dietary fat content did not have any biologically relevant effects on tetanus vaccine responses in this experiment in mice.

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Investigation of the effect of dietary fat content on obesity and metabolic syndrome in smokers

Endocrine Abstracts ◽

10.1530/endoabs.56.p596 ◽

2018 ◽

Author(s):

Salman Reyhan Bilici ◽

Gulcelik Nese Ersoz ◽

Tulay Omma

Keyword(s):

Metabolic Syndrome ◽

Dietary Fat ◽

Fat Content

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Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle

Journal of Animal Science ◽

10.2527/jas2016.0892 ◽

2017 ◽

Vol 95 (3) ◽

pp. 1313 ◽

Cited By ~ 7

Author(s):

L. Zhang ◽

L. F. Schütz ◽

C. L. Robinson ◽

M. L. Totty ◽

L. J. Spicer

Keyword(s):

Gene Expression ◽

Tight Junction ◽

Tight Junction Proteins ◽

Junction Proteins

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Faculty Opinions recommendation of Xenobiotics shape the physiology and gene expression of the active human gut microbiome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717972372.793472885 ◽

2013 ◽

Author(s):

Jan Roelof van der Meer

Keyword(s):

Gene Expression ◽

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome

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Faculty Opinions recommendation of Xenobiotics shape the physiology and gene expression of the active human gut microbiome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717972372.793470495 ◽

2013 ◽

Author(s):

Marvin Whiteley ◽

Holly Huse

Keyword(s):

Gene Expression ◽

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome

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Protein citrullination as a source of cancer neoantigens

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002549 ◽

2021 ◽

Vol 9 (6) ◽

pp. e002549

Author(s):

Hiroyuki Katayama ◽

Makoto Kobayashi ◽

Ehsan Irajizad ◽

Alejandro Sevillarno ◽

Nikul Patel ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Immune Response ◽

Protein Expression ◽

Cell Lines ◽

Cancer Cell ◽

Family Members ◽

Immunohistochemical Analysis ◽

Cancer Cell Lines ◽

Mhc Ii

BackgroundCitrulline post-translational modification of proteins is mediated by protein arginine deiminase (PADI) family members and has been associated with autoimmune diseases. The role of PADI-citrullinome in immune response in cancer has not been evaluated. We hypothesized that PADI-mediated citrullinome is a source of neoantigens in cancer that induces immune response.MethodsProtein expression of PADI family members was evaluated in 196 cancer cell lines by means of indepth proteomic profiling. Gene expression was assessed using messenger RNA data sets from The Cancer Genome Atlas. Immunohistochemical analysis of PADI2 and peptidyl-citrulline was performed using breast cancer tissue sections. Citrullinated 12–34-mer peptides in the putative Major Histocompatibility Complex-II (MHC-II) binding range were profiled in breast cancer cell lines to investigate the relationship between protein citrullination and antigen presentation. We further evaluated immunoglobulin-bound citrullinome by mass spectrometry using 156 patients with breast cancer and 113 cancer-free controls.ResultsProteomic and gene expression analyses revealed PADI2 to be highly expressed in several cancer types including breast cancer. Immunohistochemical analysis of 422 breast tumor tissues revealed increased expression of PADI2 in ER− tumors (p<0.0001); PADI2 protein expression was positively correlated (p<0.0001) with peptidyl-citrulline staining. PADI2 expression exhibited strong positive correlations with a B cell immune signature and with MHC-II-bound citrullinated peptides. Increased circulating citrullinated antigen–antibody complexes occurred among newly diagnosed breast cancer cases relative to controls (p=0.0012).ConclusionsAn immune response associated with citrullinome is a rich source of neoantigens in breast cancer with a potential for diagnostic and therapeutic applications.

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Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

mSystems ◽

10.1128/msystems.00205-17 ◽

2018 ◽

Vol 3 (3) ◽

Cited By ~ 35

Author(s):

Ce Yuan ◽

Michael B. Burns ◽

Subbaya Subramanian ◽

Ran Blekhman

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Gut Microbiota ◽

Mirna Expression ◽

Gut Microbiome ◽

Noncoding Rna ◽

Microbial Community Composition ◽

Host Cells ◽

Microbiome Composition ◽

Small Noncoding Rna

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.

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