scholarly journals Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism

2021 ◽  
Author(s):  
Trista L Thorn ◽  
Samuel B Mitchell ◽  
Yongeun Kim ◽  
Min-Ting Lee ◽  
Janine M.C. Comrie ◽  
...  

Zinc (Zn) plays a critical role in maintaining intestinal homeostasis by regulating intestinal epithelial cells, host immune cells, and gut microbiome community composition. Deletion of metal transporter Slc39a14/Zip14 causes spontaneous intestinal permeability with low-grade chronic inflammation, mild hyperinsulinemia, and greater body fat with insulin resistance in adipose, suggesting a role for ZIP14-mediated intestinal metal transport in regulating both intestinal homeostasis and systemic metabolism. Here, we showed the function of ZIP14-mediated Zn transport in the gut microbiome composition and how ZIP14-linked changes to gut microbiome community composition are correlated with changes in host metabolism. Deletion of Zip14 generated Zn-deficient epithelial cells and luminal content in the entire intestinal tract; reduced bacterial diversity and Saccharomyces cerevisiae (S. cerevisiae) overgrowth; altered host metabolome; and shifted host energy metabolism toward glucose utilization. This work provides evidence for the regulation of gut microbiome composition, host metabolome, and energy metabolism by metal transporter ZIP14.

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 726
Author(s):  
Ronald Biemann ◽  
Enrico Buß ◽  
Dirk Benndorf ◽  
Theresa Lehmann ◽  
Kay Schallert ◽  
...  

Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of metabolic syndrome. To investigate if lifestyle-induced weight loss (WL) may modulate the gut microbiome composition and its interaction with the host on a functional level, we analyzed the fecal metaproteome of 33 individuals with metabolic syndrome in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort. The 6-month WL intervention resulted in reduced BMI (−13.7%), improved insulin sensitivity (HOMA-IR, −46.1%), and reduced levels of circulating hsCRP (−39.9%), indicating metabolic syndrome reversal. The metaprotein spectra revealed a decrease of human proteins associated with gut inflammation. Taxonomic analysis revealed only minor changes in the bacterial composition with an increase of the families Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae and Verrucomicrobiaceae. Yet we detected an increased abundance of microbial metaprotein spectra that suggest an enhanced hydrolysis of complex carbohydrates. Hence, lifestyle-induced WL was associated with reduced gut inflammation and functional changes of human and microbial enzymes for carbohydrate hydrolysis while the taxonomic composition of the gut microbiome remained almost stable. The metaproteomics workflow has proven to be a suitable method for monitoring inflammatory changes in the fecal metaproteome.


Author(s):  
Kelsey M. Loupy ◽  
Christopher A. Lowry

Posttraumatic stress disorder (PTSD) is a trauma- and stressor-related disorder that is often associated with the dysregulation of multiple physiological systems, including autonomic nervous system functioning, glucocorticoid signaling, and chronic low-grade inflammation. Recent evidence suggests that persons with a diagnosis of PTSD also exhibit alterations in the composition of gut microbiomes compared to people who are trauma-exposed but do not develop PTSD. The bidirectional communication between the gut microbiome, the gut, and the brain, deemed the microbiome-gut-brain (MGB) axis, is composed of neural, neuroendocrine, and immune processes that both impact and respond to the structure of the gut microbiome. This chapter aims to outline (1) the ways in which trauma and stressor exposure may impact the gut microbiome; (2) the ways in which gut microbiome composition may influence brain function, including anxiety, and fear responses; and (3) how the bidirectional MGB axis, through interactions with several physiological circuits, may determine individual variability in resilience versus vulnerability to development of PTSD after trauma exposure.


2016 ◽  
Author(s):  
Melissa N. Conley ◽  
Carmen P. Wong ◽  
Kyle M. Duyck ◽  
Norman Hord ◽  
Emily Ho ◽  
...  

Introduction Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging”. While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of the study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age, and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 also stratify individuals by age. Discussion Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.


2021 ◽  
Vol 22 (15) ◽  
pp. 7800
Author(s):  
Sally Temraz ◽  
Farah Nassar ◽  
Firas Kreidieh ◽  
Deborah Mukherji ◽  
Ali Shamseddine ◽  
...  

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.


Author(s):  
Zoe J. Zreloff ◽  
Danielle Lange ◽  
Suzanne D. Vernon ◽  
Martha R. Carlin ◽  
Raul de Jesus Cano

Background. Inferior quality of biological material compromises data, slows discovery, and wastes research funds. The gut microbiome plays a critical role in human health and disease, yet little attention has been given to optimizing collection and processing methods of human stool. Methods. We collected the entire bowel movement from 2 healthy volunteers: one to examine stool sample heterogeneity and one to test stool sample handling parameters. Sequencing and bi-oinformatic analyses were used to examine the microbiome composition. Results. The microbiome profile varied depending on where the subsample was obtained from the stool. The exterior cortex of the stool was rich in specific phyla and deficient in others while the interior core of the stool revealed opposite microbiome profiles. Sample processing also re-sulted in varying microbiome profiles. Homogenization and stabilization at 4°C gave superior microbial diversity profiles compared to the fresh or frozen subsamples of the same stool sample. Bacterial proliferation continued in the fresh subsample when processed at ambient temperature. Bacteroidetes proliferated and Firmicutes diminished during the 30-minute processing of fresh sample. The frozen sample had good overall diversity but Proteobacteria diminished likely be-cause of the freeze/thaw. Conclusions. The microbiome profile is specific to the section of the stool being sampled. Stool sample collection, homogenization, and stabilization at 4°C for 24 hours provides a “neat”, high-quality sample of sufficient quantity that can be banked into aliquots with nearly identical microbial diversity profiles. This collection pipeline is essential to accelerate our understanding of the gut microbiome in health and disease.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1854 ◽  
Author(s):  
Melissa N. Conley ◽  
Carmen P. Wong ◽  
Kyle M. Duyck ◽  
Norman Hord ◽  
Emily Ho ◽  
...  

Introduction.Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging.” While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model.Results.We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age.Discussion.Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.


Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1113
Author(s):  
Eun-Tae Kim ◽  
Sang-Jin Lee ◽  
Tae-Yong Kim ◽  
Hyo-Gun Lee ◽  
Rahman M. Atikur ◽  
...  

Microbiota plays a critical role in the overall growth performance and health status of dairy cows, especially during their early life. Several studies have reported that fecal microbiome of neonatal calves is shifted by various factors such as diarrhea, antibiotic treatment, or environmental changes. Despite the importance of gut microbiome, a lack of knowledge regarding the composition and functions of microbiota impedes the development of new strategies for improving growth performance and disease resistance during the neonatal calf period. In this study, we utilized next-generation sequencing to monitor the time-dependent dynamics of the gut microbiota of dairy calves before weaning (1–8 weeks of age) and further investigated the microbiome changes caused by diarrhea. Metagenomic analysis revealed that continuous changes, including increasing gut microbiome diversity, occurred from 1 to 5 weeks of age. However, the composition and diversity of the fecal microbiome did not change after 6 weeks of age. The most prominent changes in the fecal microbiome composition caused by aging at family level were a decreased abundance of Bacteroidaceae and Enterobacteriaceae and an increased abundance of Prevotellaceae. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis indicated that the abundance of microbial genes associated with various metabolic pathways changed with aging. All calves with diarrhea symptoms showed drastic microbiome changes and about a week later returned to the microbiome of pre-diarrheal stage regardless of age. At phylum level, abundance of Bacteroidetes was decreased (p = 0.09) and that of Proteobacteria increased (p = 0.07) during diarrhea. PICRUSt analysis indicated that microbial metabolism-related genes, such as starch and sucrose metabolism, sphingolipid metabolism, alanine aspartate, and glutamate metabolism were significantly altered in diarrheal calves. Together, these results highlight the important implications of gut microbiota in gut metabolism and health status of neonatal dairy calves.


2020 ◽  
Author(s):  
Zoe J. Zreloff ◽  
Danielle Lange ◽  
Suzanne D. Vernon ◽  
Martha R. Carlin ◽  
Raul de Jesus Cano

Abstract Background. Inferior quality of biological material compromises data, slows discovery, and wastes research funds. The gut microbiome plays a critical role in human health and disease, yet little attention has been given to optimizing collection and processing methods of human stool. Methods. We collected the entire bowel movement from 2 healthy volunteers: one to examine stool sample heterogeneity and one to test stool sample handling parameters. Sequencing and bioinformatic analyses were used to examine the microbiome composition. Results. The microbiome profile varied depending on where the subsample was obtained from the stool. The exterior cortex of the stool was rich in specific phyla and deficient in others while the interior core of the stool revealed opposite microbiome profiles. Sample processing also resulted in varying microbiome profiles. Homogenization and stabilization at 4°C gave superior microbial diversity profiles compared to the fresh or frozen subsamples of the same stool sample. Bacterial proliferation continued in the fresh subsample when processed at ambient temperature. Bacteroidetes proliferated and Firmicutes diminished during the 30-minute processing of fresh sample. The frozen sample had good overall diversity but Proteobacteria diminished likely because of the freeze/thaw. Conclusions. The microbiome profile is specific to the section of the stool being sampled. Stool sample collection, homogenization, and stabilization at 4°C for 24 hours provides a “neat”, high-quality sample of sufficient quantity that can be banked into aliquots with nearly identical microbial diversity profiles. This collection pipeline is essential to accelerate our understanding of the gut microbiome in health and disease


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252930
Author(s):  
V. Ivashkin ◽  
Y. Poluektov ◽  
E. Kogan ◽  
O. Shifrin ◽  
A. Sheptulin ◽  
...  

Background Irritable bowel syndrome (IBS) is a pathologic condition characterized by changes in gut microbiome composition, low-grade inflammation, and disruption of intestinal wall permeability. The interaction between the gut microbiome and the disease manifestation remains unclear. The changing of tight junction proteins and cytokines expression throughout the gastrointestinal tract in IBS patients has not been studied yet. Aim of the study To assess the changes of gut microbiome composition, tight junction proteins, and cytokines expression of intestinal mucosa from the duodenum to the distal part of the colon in IBS patients and healthy volunteers. Methods In 31 IBS patients (16 patients with IBS-D; 15 patients with IBS-C) and 10 healthy volunteers the expression of CLD-2, CLD-3, CLD-5, IL-2, IL-10, and TNF-α in mucosal biopsy specimens was determined by morphological and immune-histochemical methods. The qualitative and quantitative composition of the intestinal microbiota was assessed based on 16S rRNA gene sequencing in both groups of patients. Results The expression of IL-2 and TNF-α was significantly increased in IBS patients compared with the controls (p<0.001), with a gradual increase from the duodenum to the sigmoid colon. The expression of IL-10, CLD-3, and CLD-5 in mucosal biopsy specimens of these patients was lower than in the control group (p<0.001). Increased ratios of Bacteroidetes and decreased ratios of Firmicutes were noted in IBS patients compared to healthy volunteers (p<0.05). Conclusion IBS patients have impaired gut permeability and persisting low-grade inflammation throughout the gastrointestinal tract. Changes in the gut microbiota may support or exacerbate these changes.


2016 ◽  
Author(s):  
Melissa N. Conley ◽  
Carmen P. Wong ◽  
Kyle M. Duyck ◽  
Norman Hord ◽  
Emily Ho ◽  
...  

Introduction Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging”. While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of the study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age, and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 also stratify individuals by age. Discussion Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.


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