Integrity of the Intestinal Barrier: The Involvement of Epithelial Cells and Microbiota—A Mutual Relationship

The gastrointestinal tract, which is constantly exposed to a multitude of stimuli, is considered responsible for maintaining the homeostasis of the host. It is inhabited by billions of microorganisms, the gut microbiota, which form a mutualistic relationship with the host. Although the microbiota is generally recognized as beneficial, at the same time, together with pathogens, they are a permanent threat to the host. Various populations of epithelial cells provide the first line of chemical and physical defense against external factors acting as the interface between luminal microorganisms and immunocompetent cells in lamina propria. In this review, we focus on some essential, innate mechanisms protecting mucosal integrity, thus responsible for maintaining intestine homeostasis. The characteristics of decisive cell populations involved in maintaining the barrier arrangement, based on mucus secretion, formation of intercellular junctions as well as production of antimicrobial peptides, responsible for shaping the gut microbiota, are presented. We emphasize the importance of cross-talk between gut microbiota and epithelial cells as a factor vital for the maintenance of the homeostasis of the GI tract. Finally, we discuss how the imbalance of these regulations leads to the compromised barrier integrity and dysbiosis considered to contribute to inflammatory disorders and metabolic diseases.

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Nuciferine modulates the gut microbiota and prevents obesity in high-fat diet-fed rats

Experimental & Molecular Medicine ◽

10.1038/s12276-020-00534-2 ◽

2020 ◽

Vol 52 (12) ◽

pp. 1959-1975

Author(s):

Yu Wang ◽

Weifan Yao ◽

Bo Li ◽

Shiyun Qian ◽

Binbin Wei ◽

...

Keyword(s):

Lipid Metabolism ◽

Gut Microbiota ◽

Relative Abundance ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

16S Rrna Gene Sequencing ◽

Fecal Microbiota ◽

Rrna Gene ◽

Low Grade ◽

Rrna Gene Sequencing

AbstractGut microbiota dysbiosis has a significant role in the pathogenesis of metabolic diseases, including obesity. Nuciferine (NUC) is a main bioactive component in the lotus leaf that has been used as food in China since ancient times. Here, we examined whether the anti-obesity effects of NUC are related to modulations in the gut microbiota. Using an obese rat model fed a HFD for 8 weeks, we show that NUC supplementation of HFD rats prevents weight gain, reduces fat accumulation, and ameliorates lipid metabolic disorders. Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that NUC changed the diversity and composition of the gut microbiota in HFD-fed rats. In particular, NUC decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS-producing genus Desulfovibrio and bacteria involved in lipid metabolism, whereas it increased the relative abundance of SCFA-producing bacteria in HFD-fed rats. Predicted functional analysis of microbial communities showed that NUC modified genes involved in LPS biosynthesis and lipid metabolism. In addition, serum metabolomics analysis revealed that NUC effectively improved HFD-induced disorders of endogenous metabolism, especially lipid metabolism. Notably, NUC promoted SCFA production and enhanced intestinal integrity, leading to lower blood endotoxemia to reduce inflammation in HFD-fed rats. Together, the anti-obesity effects of NUC may be related to modulations in the composition and potential function of gut microbiota, improvement in intestinal barrier integrity and prevention of chronic low-grade inflammation. This research may provide support for the application of NUC in the prevention and treatment of obesity.

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Multi-Pharmacology of Berberine in Atherosclerosis and Metabolic Diseases: Potential Contribution of Gut Microbiota

Frontiers in Pharmacology ◽

10.3389/fphar.2021.709629 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shengjie Yang ◽

Dan Li ◽

Zongliang Yu ◽

Yujuan Li ◽

Min Wu

Keyword(s):

Gut Microbiota ◽

Energy Homeostasis ◽

Metabolic Diseases ◽

Biological Effects ◽

Intestinal Barrier ◽

Isoquinoline Alkaloid ◽

Research Progress ◽

Intestinal Barrier Function ◽

Potential Contribution ◽

Nonalcoholic Fatty Liver

Atherosclerosis (AS), especially atherosclerotic cardiovascular diseases (ASCVDs), and metabolic diseases (such as diabetes, obesity, dyslipidemia, and nonalcoholic fatty liver disease) are major public health issues worldwide that seriously threaten human health. Exploring effective natural product-based drugs is a promising strategy for the treatment of AS and metabolic diseases. Berberine (BBR), an important isoquinoline alkaloid found in various medicinal plants, has been shown to have multiple pharmacological effects and therapeutic applications. In view of its low bioavailability, increasing evidence indicates that the gut microbiota may serve as a target for the multifunctional effects of BBR. Under the pathological conditions of AS and metabolic diseases, BBR improves intestinal barrier function and reduces inflammation induced by gut microbiota-derived lipopolysaccharide (LPS). Moreover, BBR reverses or induces structural and compositional alterations in the gut microbiota and regulates gut microbe-dependent metabolites as well as related downstream pathways; this improves glucose and lipid metabolism and energy homeostasis. These findings at least partly explain the effect of BBR on AS and metabolic diseases. In this review, we elaborate on the research progress of BBR and its mechanisms of action in the treatment of AS and metabolic diseases from the perspective of gut microbiota, to reveal the potential contribution of gut microbiota to the multifunctional biological effects of BBR.

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Gut Microbiota, in the Halfway between Nutrition and Lung Function

Nutrients ◽

10.3390/nu13051716 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1716

Author(s):

Christophe Espírito Santo ◽

Catarina Caseiro ◽

Maria João Martins ◽

Rosário Monteiro ◽

Inês Brandão

Keyword(s):

Lung Function ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Lung Diseases ◽

Dietary Habits ◽

Metabolic Diseases ◽

Current Knowledge ◽

Intestinal Barrier ◽

Community Interest ◽

The Impact

The gut microbiota is often mentioned as a “forgotten organ” or “metabolic organ”, given its profound impact on host physiology, metabolism, immune function and nutrition. A healthy diet is undoubtedly a major contributor for promoting a “good” microbial community that turns out to be crucial for a fine-tuned symbiotic relationship with the host. Both microbial-derived components and produced metabolites elicit the activation of downstream cascades capable to modulate both local and systemic immune responses. A balance between host and gut microbiota is crucial to keep a healthy intestinal barrier and an optimal immune homeostasis, thus contributing to prevent disease occurrence. How dietary habits can impact gut microbiota and, ultimately, host immunity in health and disease has been the subject of intense study, especially with regard to metabolic diseases. Only recently, these links have started to be explored in relation to lung diseases. The objective of this review is to address the current knowledge on how diet affects gut microbiota and how it acts on lung function. As the immune system seems to be the key player in the cross-talk between diet, gut microbiota and the lungs, involved immune interactions are discussed. There are key nutrients that, when present in our diet, help in gut homeostasis and lead to a healthier lifestyle, even ameliorating chronic diseases. Thus, with this review we hope to incite the scientific community interest to use diet as a valuable non-pharmacological addition to lung diseases management. First, we talk about the intestinal microbiota and interactions through the intestinal barrier for a better understanding of the following sections, which are the main focus of this article: the way diet impacts the intestinal microbiota and the immune interactions of the gut–lung axis that can explain the impact of diet, a key modifiable factor influencing the gut microbiota in several lung diseases.

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Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review

Nutrients ◽

10.3390/nu13093211 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3211

Author(s):

Hang-Yu Li ◽

Dan-Dan Zhou ◽

Ren-You Gan ◽

Si-Yu Huang ◽

Cai-Ning Zhao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Clinical Effects ◽

The One ◽

The Relationship ◽

Gut Microbiota Composition

Metabolic diseases are serious threats to public health and related to gut microbiota. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are powerful regulators of gut microbiota, thus possessing prospects for preventing metabolic diseases. Therefore, the effects and mechanisms of PPSP on metabolic diseases targeting gut microbiota are worth discussing and clarifying. Generally, PPSP benefit metabolic diseases management, especially obesity and type 2 diabetes mellitus. The underlying gut microbial-related mechanisms are mainly the modulation of gut microbiota composition, regulation of gut microbial metabolites, and improvement of intestinal barrier function. Moreover, clinical trials showed the benefits of PPSP on patients with metabolic diseases, while the clinical strategies for gestational diabetes mellitus, optimal formula of synbiotics and health benefits of postbiotics need further study. This review fully summarizes the relationship between probiotics, prebiotics, synbiotics, postbiotics, and metabolic diseases, presents promising results and the one in dispute, and especially attention is paid to illustrates potential mechanisms and clinical effects, which could contribute to the next research and development of PPSP.

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Intestinal Barrier in Human Health and Disease

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182312836 ◽

2021 ◽

Vol 18 (23) ◽

pp. 12836

Author(s):

Natalia Di Tommaso ◽

Antonio Gasbarrini ◽

Francesca Romana Ponziani

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Leaky Gut ◽

Barrier Dysfunction ◽

Permeable Barrier ◽

Gut Dysbiosis ◽

Health And Disease ◽

And Function ◽

The Relationship

The intestinal mucosa provides a selective permeable barrier for nutrient absorption and protection from external factors. It consists of epithelial cells, immune cells and their secretions. The gut microbiota participates in regulating the integrity and function of the intestinal barrier in a homeostatic balance. Pathogens, xenobiotics and food can disrupt the intestinal barrier, promoting systemic inflammation and tissue damage. Genetic and immune factors predispose individuals to gut barrier dysfunction, and changes in the composition and function of the gut microbiota are central to this process. The progressive identification of these changes has led to the development of the concept of ‘leaky gut syndrome’ and ‘gut dysbiosis’, which underlie the relationship between intestinal barrier impairment, metabolic diseases and autoimmunity. Understanding the mechanisms underlying this process is an intriguing subject of research for the diagnosis and treatment of various intestinal and extraintestinal diseases.

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Relationship between gut microbiota, gut hyperpermeability, and obesity

Current Medicinal Chemistry ◽

10.2174/0929867327666200721160313 ◽

2020 ◽

Vol 27 ◽

Author(s):

Amin Gasmi ◽

Pavan Kumar Mujawdiya ◽

Lyudmila Pivina ◽

Alexandru Doşa ◽

Yuliya Semenova ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Disorders ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Close Relation ◽

Low Grade ◽

Cytokine Levels ◽

Inflammatory Bowel ◽

Low Grade Inflammation ◽

The Relationship

: Intestinal hyperpermeability is a complex metabolic process mediated by different pathways in close relation to the gut microbiota. Previous studies suggested that the gut microbiota is involved in different metabolic regulations, and its imbalance is associated with several metabolic diseases, including obesity. It is well known that intestinal hyperpermeability is associated with dysbiosis, and the combination of these two conditions can lead to an increase in the level of low-grade inflammation in obese patients due to an increase in pro-inflammatory cytokine levels. Inflammatory bowel syndrome often accompanies this condition causing an alteration of the intestinal mucosa and thus reinforcing the dysbiosis and gut hyperpermeability. The onset of metabolic disorders depends on violations of the integrity of the intestinal barrier as a result of increased intestinal permeability. Chronic inflammation due to endotoxemia is responsible for the development of obesity. Metabolic disorders are associated with dysregulation of the microbiota-gut-brain axis and with an altered composition of gut flora. In this review, we will discuss the mechanisms that illustrate the relationship between hyperpermeability, the composition of the gut microbiota, and obesity.

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Berberine Ameliorates Periodontal Bone Loss by Regulating Gut Microbiota

Journal of Dental Research ◽

10.1177/0022034518797275 ◽

2018 ◽

Vol 98 (1) ◽

pp. 107-116 ◽

Cited By ~ 13

Author(s):

X. Jia ◽

L. Jia ◽

L. Mo ◽

S. Yuan ◽

X. Zheng ◽

...

Keyword(s):

Bone Loss ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Alveolar Bone ◽

Intestinal Barrier ◽

Alveolar Bone Loss ◽

Micro Computed Tomography ◽

Ovx Rats ◽

Obesity And Diabetes ◽

Periodontal Bone Loss

Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current therapeutics against PMO prevent the aggravated alveolar bone loss of periodontitis in estrogen-deficient women. Gut microbiota is recognized as a promising therapeutic target for PMO. Berberine extracted from Chinese medicinal plants has shown its effectiveness in the treatment of metabolic diseases such as obesity and diabetes via regulating gut microbiota. Here, we hypothesize that berberine ameliorates periodontal bone loss by improving the intestinal barriers by regulating gut microbiota under an estrogen-deficient condition. Experimental periodontitis was established in ovariectomized (OVX) rats, and the OVX-periodontitis rats were treated with berberine for 7 wk before sacrifice for analyses. Micro–computed tomography and histologic analyses showed that berberine treatment significantly reduced alveolar bone loss and improved bone metabolism of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher abundance of butyrate-producing gut microbiota with elevated butyrate generation, as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography analysis. Berberine-treated OVX-periodontitis rats consistently showed improved intestinal barrier integrity and decreased intestinal paracellular permeability with a lower level of serum endotoxin. In parallel, IL-17A-related immune responses were attenuated in berberine-treated OVX-periodontitis rats with a lower serum level of proinflammatory cytokines and reduced IL-17A+ cells in alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data indicate that gut microbiota is a potential target for the treatment of estrogen deficiency–aggravated periodontal bone loss, and berberine represents a promising adjuvant therapeutic by modulating gut microbiota.

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Microbial Metabolites Determine Host Health and the Status of Some Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms20215296 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5296 ◽

Cited By ~ 13

Author(s):

Panida Sittipo ◽

Jae-won Shim ◽

Yun Lee

Keyword(s):

Intestinal Microbiota ◽

Metabolic Diseases ◽

Host Cells ◽

Microbiota Composition ◽

Microbial Metabolites ◽

Gi Tract ◽

Host Health ◽

Bowel Diseases ◽

The Status ◽

Mutualistic Relationship

The gastrointestinal (GI) tract is a highly complex organ composed of the intestinal epithelium layer, intestinal microbiota, and local immune system. Intestinal microbiota residing in the GI tract engages in a mutualistic relationship with the host. Different sections of the GI tract contain distinct proportions of the intestinal microbiota, resulting in the presence of unique bacterial products in each GI section. The intestinal microbiota converts ingested nutrients into metabolites that target either the intestinal microbiota population or host cells. Metabolites act as messengers of information between the intestinal microbiota and host cells. The intestinal microbiota composition and resulting metabolites thus impact host development, health, and pathogenesis. Many recent studies have focused on modulation of the gut microbiota and their metabolites to improve host health and prevent or treat diseases. In this review, we focus on the production of microbial metabolites, their biological impact on the intestinal microbiota composition and host cells, and the effect of microbial metabolites that contribute to improvements in inflammatory bowel diseases and metabolic diseases. Understanding the role of microbial metabolites in protection against disease might offer an intriguing approach to regulate disease.

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Commensal Escherichia coli Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells

Applied and Environmental Microbiology ◽

10.1128/aem.00059-19 ◽

2019 ◽

Vol 85 (12) ◽

Cited By ~ 5

Author(s):

Junyuan Zheng ◽

Lihong Lou ◽

Junjie Fan ◽

Chunlan Huang ◽

Qixiang Mei ◽

...

Keyword(s):

Escherichia Coli ◽

Epithelial Cells ◽

Gut Microbiota ◽

Intestinal Epithelial Cells ◽

Necrotizing Pancreatitis ◽

Intestinal Barrier ◽

Intestinal Epithelial ◽

Content Type ◽

E Coli ◽

Acute Necrotizing

ABSTRACT An increase of Escherichia-Shigella was previously reported in acute necrotizing pancreatitis (ANP). We investigated whether Escherichia coli MG1655, an Escherichia commensal organism, increased intestinal injury and aggravated ANP in rats. ANP was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct. Using gut microbiota-depleted rats, we demonstrated that gut microbiota was involved in the pancreatic injury and intestinal barrier dysfunction in ANP. Using 16S rRNA gene sequencing and quantitative PCR, we found intestinal dysbiosis and a significant increase of E. coli MG1655 in ANP. Afterward, administration of E. coli MG1655 by gavage to gut microbiota-depleted rats with ANP was performed. We observed that after ANP induction, E. coli MG1655-monocolonized rats presented more severe injury in the pancreas and intestinal barrier function than gut microbiota-depleted rats. Furthermore, Toll-like receptor 4 (TLR4)/MyD88/p38 mitogen-activated protein (MAPK) and endoplasmic reticulum stress (ERS) activation in intestinal epithelial cells were also increased more significantly in the MG1655-monocolonized ANP rats. In vitro, the rat ileal epithelial cell line IEC-18 displayed aggravated tumor necrosis factor alpha-induced inflammation and loss of tight-junction proteins in coculture with E. coli MG1655, as well as TLR4, MyD88, and Bip upregulation. In conclusion, our study shows that commensal E. coli MG1655 increases TLR4/MyD88/p38 MAPK and ERS signaling-induced intestinal epithelial injury and aggravates ANP in rats. Our study also describes the harmful potential of commensal E. coli in ANP. IMPORTANCE This study describes the harmful potential of commensal E. coli in ANP, which has not been demonstrated in previous studies. Our work provides new insights into gut bacterium-ANP cross talk, suggesting that nonpathogenic commensals could also exhibit adverse effects in the context of diseases.

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Microbiota, Fiber, and NAFLD: Is There Any Connection?

Nutrients ◽

10.3390/nu12103100 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3100

Author(s):

Alejandra Pérez-Montes de Oca ◽

María Teresa Julián ◽

Analía Ramos ◽

Manel Puig-Domingo ◽

Nuria Alonso

Keyword(s):

Weight Loss ◽

Gut Microbiota ◽

Fatty Liver Disease ◽

Pathogenic Bacteria ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Alcoholic Fatty Liver ◽

Fiber Consumption ◽

Insoluble Fiber ◽

Alcoholic Fatty Liver Disease

Gut microbiota can contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD). In fact, some specific changes of gut microbiota are observed in patients in what is called dysbiota. There has been a lot of investigation by using a variety of interventions, including diet, showing the possibility to modify components of gastrointestinal dysbiota towards healthy and multivariate microbiota to restore physiologic status. One of the main focuses has been dietary fiber (DF), in which most of its variants are prebiotics. The highest effective treatment for NAFLD is, so far, weight loss achieved by caloric restriction. DF supplementation with oligofructose facilitates weight loss, enhances the production of beneficial metabolites, decreases some pathogenic bacteria population by increasing Bifidobacteria, and has effects on intestinal barrier permeability. DF use has been associated with improvement in diverse metabolic diseases, including NAFLD, by modifying gut microbiota. Additionally, it has been shown that a higher insoluble fiber consumption (≥7.5 g/day) revealed improvements in 3 different scores of liver fibrosis. Further research is needed, but given the evidence available, it is reasonable to prescribe its consumption in early stages of NAFLD in order to prevent disease progression.

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