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The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 61367

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Special Issue Editors

Prof. Dr. Raffaele Capasso

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Guest Editor

Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
Interests: pharmacology; natural products; neurotransmission; behavioral pharmacology; experimental pharmacology; preclinical pharmacology; CB1 receptor; PPARs; cannabinoids; endocannabinoids; CB2 receptor
Special Issues, Collections and Topics in MDPI journals

Dr. Giovanni Sarnelli

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Guest Editor

Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
Interests: leaky gut; diabetes and obesity; enteric nervous system; dysbiosis; dyspepsia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, knowledge about the composition and role of human microbiota has enormously increased. It has become clear that human microbiota is a complex community of bacteria, viruses, and fungi that plays a key role in maintaining health, and that its alteration, named dysbiosis, is involved in different communicable and noncommunicable diseases.

Gut microbiota is responsible for the fermentation of nondigestible fibers, resulting in the production of short chain fatty acids, nutrients further contributing to host energy production, metabolism, and immunity. Different external factors, including diet, physical activity, stress, drugs, and geographic environment may influence gut microbiota composition and functions.

This Special Issue will highlight recent research on the role of intestinal microbiota in wellbeing and will explore target therapies by focusing on potential molecular mechanisms.

Prof. Dr. Raffaele Capasso
Dr. Giovanni Sarnelli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Microbiota
Obesity
Gut–brain axis
Diet
Metabolic syndrome
Polyunsaturated fatty acids
Fiber-rich diet
Dysbiosis
Hepatic inflammation
Immunometabolism
Host defense
Metabolism
Wellness

Published Papers (10 papers)

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Research

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14 pages, 1688 KiB

Open AccessArticle

Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice

by Giuseppe Esposito, Marcella Pesce, Luisa Seguella, Jie Lu, Chiara Corpetti, Alessandro Del Re, Fatima Domenica Elisa De Palma, Giovanni Esposito, Walter Sanseverino and Giovanni Sarnelli

Int. J. Mol. Sci. 2021, 22(6), 2945; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062945 - 14 Mar 2021

Cited by 16 | Viewed by 3154

Abstract

Palmitoylethanolamide (PEA) is an N-acylethanolamide produced on-demand by the enzyme N-acylphosphatidylethanolamine-preferring phospholipase D (NAPE-PLD). Being a key member of the larger family of bioactive autacoid local injury antagonist amides (ALIAmides), PEA significantly improves the clinical and histopathological stigmata in models of ulcerative colitis (UC). Despite its safety profile, high PEA doses are required in vivo to exert its therapeutic activity; therefore, PEA has been tested only in animals or human biopsy samples, to date. To overcome these limitations, we developed an NAPE-PLD-expressing Lactobacillus paracasei F19 (pNAPE-LP), able to produce PEA under the boost of ultra-low palmitate supply, and investigated its therapeutic potential in a murine model of UC. The coadministration of pNAPE-LP and palmitate led to a time-dependent release of PEA, resulting in a significant amelioration of the clinical and histological damage score, with a significantly reduced neutrophil infiltration, lower expression and release of pro-inflammatory cytokines and oxidative stress markers, and a markedly improved epithelial barrier integrity. We concluded that pNAPE-LP with ultra-low palmitate supply stands as a new method to increase the in situ intestinal delivery of PEA and as a new therapeutic able of controlling intestinal inflammation in inflammatory bowel disease. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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15 pages, 5491 KiB

Open AccessArticle

High-Fat Diets with Differential Fatty Acids Induce Obesity and Perturb Gut Microbiota in Honey Bee

by Xiaofei Wang, Zhaopeng Zhong, Xiangyin Chen, Ziyun Hong, Weimin Lin, Xiaohuan Mu, Xiaosong Hu and Hao Zheng

Int. J. Mol. Sci. 2021, 22(2), 834; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020834 - 15 Jan 2021

Cited by 12 | Viewed by 4075

Abstract

HFD (high-fat diet) induces obesity and metabolic disorders, which is associated with the alteration in gut microbiota profiles. However, the underlying molecular mechanisms of the processes are poorly understood. In this study, we used the simple model organism honey bee to explore how different amounts and types of dietary fats affect the host metabolism and the gut microbiota. Excess dietary fat, especially palm oil, elicited higher weight gain, lower survival rates, hyperglycemic, and fat accumulation in honey bees. However, microbiota-free honey bees reared on high-fat diets did not significantly change their phenotypes. Different fatty acid compositions in palm and soybean oil altered the lipid profiles of the honey bee body. Remarkably, dietary fats regulated lipid metabolism and immune-related gene expression at the transcriptional level. Gene set enrichment analysis showed that biological processes, including transcription factors, insulin secretion, and Toll and Imd signaling pathways, were significantly different in the gut of bees on different dietary fats. Moreover, a high-fat diet increased the relative abundance of Gilliamella, while the level of Bartonella was significantly decreased in palm oil groups. This study establishes a novel honey bee model of studying the crosstalk between dietary fat, gut microbiota, and host metabolism. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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12 pages, 1213 KiB

Open AccessArticle

Impact of a Model Used to Simulate Chronic Socio-Environmental Stressors Encountered during Spaceflight on Murine Intestinal Microbiota

by Corentine Alauzet, Lisiane Cunat, Maxime Wack, Laurence Lanfumey, Christine Legrand-Frossi, Alain Lozniewski, Nelly Agrinier, Catherine Cailliez-Grimal and Jean-Pol Frippiat

Int. J. Mol. Sci. 2020, 21(21), 7863; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217863 - 23 Oct 2020

Cited by 11 | Viewed by 1903

Abstract

During deep-space travels, crewmembers face various physical and psychosocial stressors that could alter gut microbiota composition. Since it is well known that intestinal dysbiosis is involved in the onset or exacerbation of several disorders, the aim of this study was to evaluate changes in intestinal microbiota in a murine model used to mimic chronic psychosocial stressors encountered during a long-term space mission. We demonstrate that 3 weeks of exposure to this model (called CUMS for Chronic Unpredictable Mild Stress) induce significant change in intracaecal β-diversity characterized by an important increase of the Firmicutes/Bacteroidetes ratio. These alterations are associated with a decrease of Porphyromonadaceae, particularly of the genus Barnesiella, a major member of gut microbiota in mice and humans where it is described as having protective properties. These results raise the question of the impact of stress-induced decrease of beneficial taxa, support recent data deduced from in-flight experimentations and other ground-based models, and emphasize the critical need for further studies exploring the impact of spaceflight on intestinal microbiota in order to propose strategies to countermeasure spaceflight-associated dysbiosis and its consequences on health. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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13 pages, 908 KiB

Open AccessArticle

Colonic Mucosal Microbiota and Association of Bacterial Taxa with the Expression of Host Antimicrobial Peptides in Pediatric Ulcerative Colitis

by Jonna Jalanka, Jing Cheng, Kaisa Hiippala, Jarmo Ritari, Jarkko Salojärvi, Tarja Ruuska, Marko Kalliomäki and Reetta Satokari

Int. J. Mol. Sci. 2020, 21(17), 6044; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176044 - 22 Aug 2020

Cited by 20 | Viewed by 3626

Abstract

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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Review

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18 pages, 1692 KiB

Open AccessReview

Butyrate and the Fine-Tuning of Colonic Homeostasis: Implication for Inflammatory Bowel Diseases

by Naschla Gasaly, Marcela A. Hermoso and Martín Gotteland

Int. J. Mol. Sci. 2021, 22(6), 3061; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063061 - 17 Mar 2021

Cited by 73 | Viewed by 7679

Abstract

This review describes current evidence supporting butyrate impact in the homeostatic regulation of the digestive ecosystem in health and inflammatory bowel diseases (IBDs). Butyrate is mainly produced by bacteria from the Firmicutes phylum. It stimulates mature colonocytes and inhibits undifferentiated malignant and stem cells. Butyrate oxidation in mature colonocytes (1) produces 70–80% of their energetic requirements, (2) prevents stem cell inhibition by limiting butyrate access to crypts, and (3) consumes oxygen, generating hypoxia and maintaining luminal anaerobiosis favorable to the microbiota. Butyrate stimulates the aryl hydrocarbon receptor (AhR), the GPR41 and GPR109A receptors, and inhibits HDAC in different cell types, thus stabilizing the gut barrier function and decreasing inflammatory processes. However, some studies indicate contrary effects according to butyrate concentrations. IBD patients exhibit a lower abundance of butyrate-producing bacteria and butyrate content. Additionally, colonocyte butyrate oxidation is depressed in these subjects, lowering luminal anaerobiosis and facilitating the expansion of Enterobacteriaceae that contribute to inflammation. Accordingly, gut dysbiosis and decreased barrier function in IBD seems to be secondary to the impaired mitochondrial disturbance in colonic epithelial cells. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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42 pages, 2878 KiB

Open AccessReview

Impact of Microbial Metabolites on Microbiota–Gut–Brain Axis in Inflammatory Bowel Disease

by Davide Banfi, Elisabetta Moro, Annalisa Bosi, Michela Bistoletti, Silvia Cerantola, Francesca Crema, Fabrizio Maggi, Maria Cecilia Giron, Cristina Giaroni and Andreina Baj

Int. J. Mol. Sci. 2021, 22(4), 1623; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041623 - 05 Feb 2021

Cited by 52 | Viewed by 9396

Abstract

The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the “gut–brain axis” and renamed the “microbiota–gut–brain axis”, considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota–gut–brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as “postbiotics”, such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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24 pages, 897 KiB

Open AccessReview

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

by Kara Sampsell, Desirée Hao and Raylene A. Reimer

Int. J. Mol. Sci. 2020, 21(23), 9239; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239239 - 03 Dec 2020

Cited by 30 | Viewed by 6612

Abstract

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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19 pages, 1060 KiB

Open AccessReview

A Budding Relationship: Bacterial Extracellular Vesicles in the Microbiota-Gut-Brain Axis

by Sandor Haas-Neill and Paul Forsythe

Int. J. Mol. Sci. 2020, 21(23), 8899; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238899 - 24 Nov 2020

Cited by 38 | Viewed by 6290

Abstract

The discovery of the microbiota-gut-brain axis has revolutionized our understanding of systemic influences on brain function and may lead to novel therapeutic approaches to neurodevelopmental and mood disorders. A parallel revolution has occurred in the field of intercellular communication, with the realization that endosomes, and other extracellular vesicles, rival the endocrine system as regulators of distant tissues. These two paradigms shifting developments come together in recent observations that bacterial membrane vesicles contribute to inter-kingdom signaling and may be an integral component of gut microbe communication with the brain. In this short review we address the current understanding of the biogenesis of bacterial membrane vesicles and the roles they play in the survival of microbes and in intra and inter-kingdom communication. We identify recent observations indicating that bacterial membrane vesicles, particularly those derived from probiotic organisms, regulate brain function. We discuss mechanisms by which bacterial membrane vesicles may influence the brain including interaction with the peripheral nervous system, and modulation of immune activity. We also review evidence suggesting that, unlike the parent organism, gut bacteria derived membrane vesicles are able to deliver cargo, including neurotransmitters, directly to the central nervous system and may thus constitute key components of the microbiota-gut-brain axis. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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25 pages, 1182 KiB

Open AccessReview

Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome

by Yoshiyuki Mishima and Shunji Ishihara

Int. J. Mol. Sci. 2020, 21(22), 8664; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228664 - 17 Nov 2020

Cited by 50 | Viewed by 8061

Abstract

Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders, and accumulating evidence gained in both preclinical and clinical studies indicate the involvement of enteric microbiota in its pathogenesis. Gut resident microbiota appear to influence brain activity through the enteric nervous system, while their composition and function are affected by the central nervous system. Based on these results, the term “brain–gut–microbiome axis” has been proposed and enteric microbiota have become a potential therapeutic target in IBS cases. However, details regarding the microbe-related pathophysiology of IBS remain elusive. This review summarizes the existing knowledge of molecular mechanisms in the pathogenesis of IBS as well as recent progress related to microbiome-derived neurotransmitters, compounds, metabolites, neuroendocrine factors, and enzymes. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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Graphical abstract

20 pages, 1424 KiB

Open AccessReview

The Molecular and Mechanistic Insights Based on Gut–Liver Axis: Nutritional Target for Non-Alcoholic Fatty Liver Disease (NAFLD) Improvement

by Yun Ji, Yue Yin, Lijun Sun and Weizhen Zhang

Int. J. Mol. Sci. 2020, 21(9), 3066; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093066 - 26 Apr 2020

Cited by 74 | Viewed by 9486

Abstract

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most frequent classification of liver disease around the globe. Along with the sequencing technologies, gut microbiota has been regarded as a vital factor for the maintenance of human and animal health and the mediation of multiple diseases. The modulation of gut microbiota as a mechanism affecting the pathogenesis of NAFLD is becoming a growing area of concern. Recent advances in the communication between gut and hepatic tissue pave novel ways to better explain the molecular mechanisms regarding the pathological physiology of NAFLD. In this review, we recapitulate the current knowledge of the mechanisms correlated with the development and progression of NAFLD regulated by the gut microbiome and gut–liver axis, which may provide crucial therapeutic strategies for NAFLD. These mechanisms predominantly involve: (1) the alteration in gut microbiome profile; (2) the effects of components and metabolites from gut bacteria (e.g., lipopolysaccharides (LPS), trimethylamine-N-oxide (TMAO), and N,N,N-trimethyl-5-aminovaleric acid (TMAVA)); and (3) the impairment of intestinal barrier function and bile acid homeostasis. In particular, the prevention and therapy of NAFLD assisted by nutritional strategies are highlighted, including probiotics, functional oligosaccharides, dietary fibers, ω-3 polyunsaturated fatty acids, functional amino acids (L-tryptophan and L-glutamine), carotenoids, and polyphenols, based on the targets excavated from the gut–liver axis. Full article

(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)

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