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13 pages, 3122 KiB

Open AccessArticle

The Divergent Immunomodulatory Effects of Short Chain Fatty Acids and Medium Chain Fatty Acids

by Qi Hui Sam, Hua Ling, Wen Shan Yew, Zhaohong Tan, Sharada Ravikumar, Matthew Wook Chang and Louis Yi Ann Chai

Int. J. Mol. Sci. 2021, 22(12), 6453; https://doi.org/10.3390/ijms22126453 - 16 Jun 2021

Cited by 37 | Viewed by 4506

Abstract

Fatty acids are derived from diet and fermentative processes by the intestinal flora. Two to five carbon chain fatty acids, termed short chain fatty acids (SCFA) are increasingly recognized to play a role in intestinal homeostasis. However, the characteristics of slightly longer 6 [...] Read more.

Fatty acids are derived from diet and fermentative processes by the intestinal flora. Two to five carbon chain fatty acids, termed short chain fatty acids (SCFA) are increasingly recognized to play a role in intestinal homeostasis. However, the characteristics of slightly longer 6 to 10 carbon, medium chain fatty acids (MCFA), derived primarily from diet, are less understood. Here, we demonstrated that SCFA and MCFA have divergent immunomodulatory propensities. SCFA down-attenuated host pro-inflammatory IL-1β, IL-6, and TNFα response predominantly through the TLR4 pathway, whereas MCFA augmented inflammation through TLR2. Butyric (C4) and decanoic (C10) acid displayed most potent modulatory effects within the SCFA and MCFA, respectively. Reduction in TRAF3, IRF3 and TRAF6 expression were observed with butyric acid. Decanoic acid induced up-regulation of GPR84 and PPARγ and altered HIF-1α/HIF-2α ratio. These variant immune characteristics of the fatty acids which differ by just several carbon atoms may be attributable to their origins, with SCFA being primarily endogenous and playing a physiological role, and MCFA exogenously from the diet. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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19 pages, 2584 KiB

Open AccessArticle

Erythritol Ameliorates Small Intestinal Inflammation Induced by High-Fat Diets and Improves Glucose Tolerance

by Rena Kawano, Takuro Okamura, Yoshitaka Hashimoto, Saori Majima, Takafumi Senmaru, Emi Ushigome, Mai Asano, Masahiro Yamazaki, Hiroshi Takakuwa, Ryoichi Sasano, Naoko Nakanishi, Masahide Hamaguchi and Michiaki Fukui

Int. J. Mol. Sci. 2021, 22(11), 5558; https://doi.org/10.3390/ijms22115558 - 24 May 2021

Cited by 24 | Viewed by 4181

Abstract

Background: Erythritol, a sugar alcohol, is widely used as a substitute for sugar in diets for patients with diabetes or obesity. Methods: In this study, we aimed to investigate the effects of erythritol on metabolic disorders induced by a high-fat diet in C57BL/6J [...] Read more.

Background: Erythritol, a sugar alcohol, is widely used as a substitute for sugar in diets for patients with diabetes or obesity. Methods: In this study, we aimed to investigate the effects of erythritol on metabolic disorders induced by a high-fat diet in C57BL/6J mice, while focusing on changes in innate immunity. Results: Mice that were fed a high-fat diet and administered water containing 5% erythritol (Ery group) had markedly lower body weight, improved glucose tolerance, and markedly higher energy expenditure than the control mice (Ctrl group) (n = 6). Furthermore, compared with the Ctrl group, the Ery group had lesser fat deposition in the liver, smaller adipocytes, and significantly better inflammatory findings in the small intestine. The concentrations of short-chain fatty acids (SCFAs), such as acetic acid, propanoic acid, and butanoic acid, in the serum, feces, and white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. In flow cytometry experiments, group 3 innate lymphoid cell (ILC3) counts in the lamina propria of the small intestine and ILC2 counts in the white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. Quantitative real-time reverse transcription polymerase chain reaction analyses showed that the Il-22 expression in the small intestine of the Ery group was markedly higher than that in the Ctrl group. Conclusions: Erythritol markedly decreased metabolic disorders such as diet-induced obesity, glucose intolerance, dyslipidemia, and fat accumulation in the mouse liver by increasing SCFAs and modulating innate immunity. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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16 pages, 1921 KiB

Open AccessArticle

A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis

by Brandi Miller, Rabina Mainali, Ravinder Nagpal and Hariom Yadav

Int. J. Mol. Sci. 2021, 22(4), 1647; https://doi.org/10.3390/ijms22041647 - 06 Feb 2021

Cited by 14 | Viewed by 4936

Abstract

The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be [...] Read more.

The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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12 pages, 281 KiB

Open AccessArticle

The Associations of SCFA with Anthropometric Parameters and Carbohydrate Metabolism in Pregnant Women

by Małgorzata Szczuko, Justyna Kikut, Dominika Maciejewska, Danuta Kulpa, Zbigniew Celewicz and Maciej Ziętek

Int. J. Mol. Sci. 2020, 21(23), 9212; https://doi.org/10.3390/ijms21239212 - 03 Dec 2020

Cited by 23 | Viewed by 2465

Abstract

Short-chain fatty acids (SCFAs) mediate the transmission of signals between the microbiome and the immune system and are responsible for maintaining balance in the anti-inflammatory reaction. Pregnancy stages alter the gut microbiota community structure, which also synthesizes SCFAs. The study involved 90 pregnant [...] Read more.

Short-chain fatty acids (SCFAs) mediate the transmission of signals between the microbiome and the immune system and are responsible for maintaining balance in the anti-inflammatory reaction. Pregnancy stages alter the gut microbiota community structure, which also synthesizes SCFAs. The study involved 90 pregnant women, divided into two groups: 48 overweight/obese pregnant women (OW) and 42 pregnant women with normal BMI (CG). The blood samples for glucose, insulin, and HBA1c were analyzed as well as stool samples for SCFA isolation (C2:0; C3:0; C4:0i; C4:0n; C5:0i; C5:0n; C6:0i; C6:0n) using gas chromatography. The SCFA profile in the analyzed groups differed significantly. A significant positive correlation between C2:0, C3:0, C4:0n and anthropometric measurements, and between C2:0, C3:0, C4:0n, and C5:0n and parameters of carbohydrate metabolism was found. SCFA levels fluctuate during pregnancy and the course of pregnancy and participate in the change in carbohydrate metabolism as well. The influence of C2:0 during pregnancy on anthropometric parameters was visible in both groups (normal weight and obese). Butyrate and propionate regulate glucose metabolism by stimulating the process of intestinal gluconeogenesis. The level of propionic acid decreases with the course of pregnancy, while its increase is characteristic of obese women, which is associated with many metabolic adaptations. Propionic and linear caproic acid levels can be an important critical point in maintaining lower anthropometric parameters during pregnancy. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

15 pages, 2501 KiB

Open AccessArticle

Targeting on Gut Microbiota-Derived Metabolite Trimethylamine to Protect Adult Male Rat Offspring against Hypertension Programmed by Combined Maternal High-Fructose Intake and Dioxin Exposure

by Chien-Ning Hsu, Julie Y. H. Chan, Hong-Ren Yu, Wei-Chia Lee, Kay L. H. Wu, Guo-Ping Chang-Chien, Sufan Lin, Chih-Yao Hou and You-Lin Tain

Int. J. Mol. Sci. 2020, 21(15), 5488; https://doi.org/10.3390/ijms21155488 - 31 Jul 2020

Cited by 20 | Viewed by 3005

Abstract

Gut microbiota-dependent metabolites, in particular trimethylamine (TMA), are linked to hypertension. Maternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or consumption of food high in fructose (HFR) can induce hypertension in adult offspring. We examined whether 3,3-maternal dimethyl-1-butanol (DMB, an inhibitor of TMA formation) therapy can protect [...] Read more.

Gut microbiota-dependent metabolites, in particular trimethylamine (TMA), are linked to hypertension. Maternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or consumption of food high in fructose (HFR) can induce hypertension in adult offspring. We examined whether 3,3-maternal dimethyl-1-butanol (DMB, an inhibitor of TMA formation) therapy can protect adult offspring against hypertension arising from combined HFR and TCDD exposure. Pregnant Sprague–Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) throughout pregnancy and lactation. Additionally, the pregnant dams received TCDD (200 ng/kg BW orally) or a corn oil vehicle on days 14 and 21 of gestation, and days 7 and 14 after birth. Some mother rats received 1% DMB in their drinking water throughout pregnancy and lactation. Six groups of male offspring were studied (n = 8 for each group): regular chow (CV), high-fructose diet (HFR), regular diet+TCDD exposure (CT), HFR+TCDD exposure (HRT), high-fructose diet+DMB treatment (HRD), and HFR+TCDD+DMB treatment (HRTD). Our data showed that TCDD exacerbates HFR-induced elevation of blood pressure in male adult offspring, which was prevented by maternal DMB administration. We observed that different maternal insults induced distinct enterotypes in adult offspring. The beneficial effects of DMB are related to alterations of gut microbiota, the increase in nitric oxide (NO) bioavailability, the balance of the renin-angiotensin system, and antagonization of aryl hydrocarbon receptor (AHR) signaling. Our findings cast new light on the role of early intervention targeting of the gut microbiota-dependent metabolite TMA, which may allow us to prevent the development of hypertension programmed by maternal excessive fructose intake and environmental dioxin exposure. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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Review

Jump to: Research

19 pages, 1201 KiB

Open AccessReview

Comparative Analysis of the Microbiome across the Gut–Skin Axis in Atopic Dermatitis

by Dong Hoon Park, Joo Wan Kim, Hi-Joon Park and Dae-Hyun Hahm

Int. J. Mol. Sci. 2021, 22(8), 4228; https://doi.org/10.3390/ijms22084228 - 19 Apr 2021

Cited by 25 | Viewed by 9051

Abstract

Atopic dermatitis (AD) is a refractory and relapsing skin disease with a complex and multifactorial etiology. Various congenital malformations and environmental factors are thought to be involved in the onset of the disease. The etiology of the disease has been investigated, with respect [...] Read more.

Atopic dermatitis (AD) is a refractory and relapsing skin disease with a complex and multifactorial etiology. Various congenital malformations and environmental factors are thought to be involved in the onset of the disease. The etiology of the disease has been investigated, with respect to clinical skin symptoms and systemic immune response factors. A gut microbiome–mediated connection between emotional disorders such as depression and anxiety, and dermatologic conditions such as acne, based on the comorbidities of these two seemingly unrelated disorders, has long been hypothesized. Many aspects of this gut–brain–skin integration theory have recently been revalidated to identify treatment options for AD with the recent advances in metagenomic analysis involving powerful sequencing techniques and bioinformatics that overcome the need for isolation and cultivation of individual microbial strains from the skin or gut. Comparative analysis of microbial clusters across the gut–skin axis can provide new information regarding AD research. Herein, we provide a historical perspective on the modern investigation and clinical implications of gut–skin connections in AD in terms of the integration between the two microbial clusters. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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34 pages, 3587 KiB

Open AccessReview

The Multiomics Analyses of Fecal Matrix and Its Significance to Coeliac Disease Gut Profiling

by Sheeana Gangadoo, Piumie Rajapaksha Pathirannahalage, Samuel Cheeseman, Yen Thi Hoang Dang, Aaron Elbourne, Daniel Cozzolino, Kay Latham, Vi Khanh Truong and James Chapman

Int. J. Mol. Sci. 2021, 22(4), 1965; https://doi.org/10.3390/ijms22041965 - 17 Feb 2021

Cited by 4 | Viewed by 4115

Abstract

Gastrointestinal (GIT) diseases have risen globally in recent years, and early detection of the host’s gut microbiota, typically through fecal material, has become a crucial component for rapid diagnosis of such diseases. Human fecal material is a complex substance composed of undigested macromolecules [...] Read more.

Gastrointestinal (GIT) diseases have risen globally in recent years, and early detection of the host’s gut microbiota, typically through fecal material, has become a crucial component for rapid diagnosis of such diseases. Human fecal material is a complex substance composed of undigested macromolecules and particles, and the processing of such matter is a challenge due to the unstable nature of its products and the complexity of the matrix. The identification of these products can be used as an indication for present and future diseases; however, many researchers focus on one variable or marker looking for specific biomarkers of disease. Therefore, the combination of genomics, transcriptomics, proteomics and metabonomics can give a detailed and complete insight into the gut environment. The proper sample collection, sample preparation and accurate analytical methods play a crucial role in generating precise microbial data and hypotheses in gut microbiome research, as well as multivariate data analysis in determining the gut microbiome functionality in regard to diseases. This review summarizes fecal sample protocols involved in profiling coeliac disease. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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23 pages, 760 KiB

Open AccessReview

Nanoparticles in the Food Industry and Their Impact on Human Gut Microbiome and Diseases

by Merry Ghebretatios, Sabrina Schaly and Satya Prakash

Int. J. Mol. Sci. 2021, 22(4), 1942; https://doi.org/10.3390/ijms22041942 - 16 Feb 2021

Cited by 36 | Viewed by 7232

Abstract

The use of inorganic nanoparticles (NPs) has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about how they may impact human health. As the gut microbiome [...] Read more.

The use of inorganic nanoparticles (NPs) has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about how they may impact human health. As the gut microbiome continues to be increasingly implicated in various diseases of unknown etiology, researchers have begun studying the potentially toxic effects of these NPs on the gut microbiome. Unfortunately, conflicting results have limited researcher’s ability to evaluate the true impact of NPs on the gut microbiome in relation to health. This review focuses on the impact of five inorganic NPs (silver, iron oxide, zinc oxide, titanium dioxide, and silicon dioxide) on the gut microbiome and gastrointestinal tract with consideration for various methodological differences within the literature. This is important as NP-induced changes to the gut could lead to various gut-related diseases. These include irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac disease, and colorectal cancer. Research in this area is necessary as the use of NPs in various industries continues to grow along with the number of people suffering from chronic gastrointestinal diseases. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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18 pages, 2653 KiB

Open AccessReview

Recent Advances of Microbiome-Associated Metabolomics Profiling in Liver Disease: Principles, Mechanisms, and Applications

by Ganesan Raja, Haripriya Gupta, Yoseph Asmelash Gebru, Gi Soo Youn, Ye Rin Choi, Hyeong Seop Kim, Sang Jun Yoon, Dong Joon Kim, Tae-Jin Kim and Ki Tae Suk

Int. J. Mol. Sci. 2021, 22(3), 1160; https://doi.org/10.3390/ijms22031160 - 25 Jan 2021

Cited by 24 | Viewed by 4847

Abstract

Advances in high-throughput screening of metabolic stability in liver and gut microbiota are able to identify and quantify small-molecule metabolites (metabolome) in different cellular microenvironments that are closest to their phenotypes. Metagenomics and metabolomics are largely recognized to be the “-omics” disciplines for [...] Read more.

Advances in high-throughput screening of metabolic stability in liver and gut microbiota are able to identify and quantify small-molecule metabolites (metabolome) in different cellular microenvironments that are closest to their phenotypes. Metagenomics and metabolomics are largely recognized to be the “-omics” disciplines for clinical therapeutic screening. Here, metabolomics activity screening in liver disease (LD) and gut microbiomes has significantly delivered the integration of metabolomics data (i.e., a set of endogenous metabolites) with metabolic pathways in cellular environments that can be tested for biological functions (i.e., phenotypes). A growing literature in LD and gut microbiomes reports the use of metabolites as therapeutic targets or biomarkers. Although growing evidence connects liver fibrosis, cirrhosis, and hepatocellular carcinoma, the genetic and metabolic factors are still mainly unknown. Herein, we reviewed proof-of-concept mechanisms for metabolomics-based LD and gut microbiotas’ role from several studies (nuclear magnetic resonance, gas/lipid chromatography, spectroscopy coupled with mass spectrometry, and capillary electrophoresis). A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to improve liver health. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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28 pages, 983 KiB

Open AccessReview

Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery

by Marc Micó-Carnero, Carlos Rojano-Alfonso, Ana Isabel Álvarez-Mercado, Jordi Gracia-Sancho, Araní Casillas-Ramírez and Carmen Peralta

Int. J. Mol. Sci. 2021, 22(1), 44; https://doi.org/10.3390/ijms22010044 - 22 Dec 2020

Cited by 15 | Viewed by 3360

Abstract

Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, [...] Read more.

Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut–liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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12 pages, 16201 KiB

Open AccessReview

Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State

by Bilal Ahmad Paray, Mohammed Fahad Albeshr, Arif Tasleem Jan and Irfan A. Rather

Int. J. Mol. Sci. 2020, 21(24), 9770; https://doi.org/10.3390/ijms21249770 - 21 Dec 2020

Cited by 45 | Viewed by 14703

Abstract

Damage to the tissue and the ruining of functions characterize autoimmune syndromes. This review centers around leaky gut syndromes and how they stimulate autoimmune pathogenesis. Lymphoid tissue commonly associated with the gut, together with the neuroendocrine network, collaborates with the intestinal epithelial wall, [...] Read more.

Damage to the tissue and the ruining of functions characterize autoimmune syndromes. This review centers around leaky gut syndromes and how they stimulate autoimmune pathogenesis. Lymphoid tissue commonly associated with the gut, together with the neuroendocrine network, collaborates with the intestinal epithelial wall, with its paracellular tight junctions, to maintain the balance, tolerance, and resistance to foreign/neo-antigens. The physiological regulator of paracellular tight junctions plays a vital role in transferring macromolecules across the intestinal barrier and thereby maintains immune response equilibrium. A new paradigm has explained the intricacies of disease development and proposed that the processes can be prevented if the interaction between the genetic factor and environmental causes is barred by re-instituting the intestinal wall function. The latest clinical evidence and animal models reinforce this current thought and offer the basis for innovative methodologies to thwart and treat autoimmune syndromes. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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21 pages, 306 KiB

Open AccessReview

The Role of Short-Chain Fatty Acids in the Interplay between a Very Low-Calorie Ketogenic Diet and the Infant Gut Microbiota and Its Therapeutic Implications for Reducing Asthma

by Naser A. Alsharairi

Int. J. Mol. Sci. 2020, 21(24), 9580; https://doi.org/10.3390/ijms21249580 - 16 Dec 2020

Cited by 27 | Viewed by 5544

Abstract

Gut microbiota is well known as playing a critical role in inflammation and asthma development. The very low-calorie ketogenic diet (VLCKD) is suggested to affect gut microbiota; however, the effects of VLCKD during pregnancy and lactation on the infant gut microbiota are unclear. [...] Read more.

Gut microbiota is well known as playing a critical role in inflammation and asthma development. The very low-calorie ketogenic diet (VLCKD) is suggested to affect gut microbiota; however, the effects of VLCKD during pregnancy and lactation on the infant gut microbiota are unclear. The VLCKD appears to be more effective than caloric/energy restriction diets for the treatment of several diseases, such as obesity and diabetes. However, whether adherence to VLCKD affects the infant gut microbiota and the protective effects thereof on asthma remains uncertain. The exact mechanisms underlying this process, and in particular the potential role of short chain fatty acids (SCFAs), are still to be unravelled. Thus, the aim of this review is to identify the potential role of SCFAs that underlie the effects of VLCKD during pregnancy and lactation on the infant gut microbiota, and explore whether it incurs significant implications for reducing asthma. Full article

(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)

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