Therapeutic Potential of the Microbiome

A special issue of Medical Sciences (ISSN 2076-3271).

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 106550

Special Issue Editor

Special Issue Information

Dear Colleagues,

In recent years, the gut microbiota has been extensively studied and has emerged as a promising therapy of gastrointestinal and extra-gastrointestinal diseases.

The human gut microbiota constitutes a very complex ecosystem containing approximately 1014 microorganisms belonging to more than 1000 species. It consists mostly of bacteria, but fungi, viruses and protozoa can also frequently be detected in the gut.  The gut microbiota has important functions for human health. The pathologic alteration of its composition, termed dysbiosis, has been linked to multiple gastrointestinal (Clostridium difficile colitis, inflammatory bowel disease, irritable bowel syndrome, etc.) and non-gastrointestinal diseases (obesity, metabolic syndrome, neuropsychiatric diseases, etc.).

Modulation of the gut microbiota with fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (FDI). Recent studies also suggest that the intestinal microbiome is involved in the pathogenesis of several chronic diseases, such as obesity, type 2 diabetes, cardiovascular, cancer or inflammatory bowel disease, and irritable bowel syndrome. In fact, the manipulation of fecal microbiota to treat inflammatory bowel disease and irritable bowel syndrome is being studied. There is also evidence that targeting gut microbiota through dietary interventions could be a potential therapeutic approach.

On these grounds, in this Special Issue of Medical Sciences we welcome research articles, reviews and communications to present the most recent advances in the study of the therapeutic potential of the microbiome.

Prof. Peter C. Konturek
Guest Editor

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Published Papers (10 papers)

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Review

17 pages, 1063 KiB  
Review
The Use of Probiotic Therapy to Modulate the Gut Microbiota and Dendritic Cell Responses in Inflammatory Bowel Diseases
by Pablo Alagón Fernández del Campo, Alejandro De Orta Pando, Juan Ignacio Straface, José Ricardo López Vega, Diego Toledo Plata, Sebastian Felipe Niezen Lugo, Diego Alvarez Hernández, Tomás Barrientos Fortes, Laila Gutiérrez-Kobeh, Sandra Georgina Solano-Gálvez and Rosalino Vázquez-López
Med. Sci. 2019, 7(2), 33; https://doi.org/10.3390/medsci7020033 - 22 Feb 2019
Cited by 14 | Viewed by 6080
Abstract
Recent investigations have shown that different conditions such as diet, the overuse of antibiotics or the colonization of pathogenic microorganisms can alter the population status of the intestinal microbiota. This modification can produce a change from homeostasis to a condition known as imbalance [...] Read more.
Recent investigations have shown that different conditions such as diet, the overuse of antibiotics or the colonization of pathogenic microorganisms can alter the population status of the intestinal microbiota. This modification can produce a change from homeostasis to a condition known as imbalance or dysbiosis; however, the role-played by dysbiosis and the development of inflammatory bowel diseases (IBD) has been poorly understood. It was actually not until a few years ago that studies started to develop regarding the role that dendritic cells (DC) of intestinal mucosa play in the sensing of the gut microbiota population. The latest studies have focused on describing the DC modulation, specifically on tolerance response involving T regulatory cells or on the inflammatory response involving reactive oxygen species and tissue damage. Furthermore, the latest studies have also focused on the protective and restorative effect of the population of the gut microbiota given by probiotic therapy, targeting IBD and other intestinal pathologies. In the present work, the authors propose and summarize a recently studied complex axis of interaction between the population of the gut microbiota, the sensing of the DC and its modulation towards tolerance and inflammation, the development of IBD and the protective and restorative effect of probiotics on other intestinal pathologies. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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14 pages, 324 KiB  
Review
Therapeutic Potential of the Microbiome in the Treatment of Neuropsychiatric Disorders
by Alper Evrensel, Barış Önen Ünsalver and Mehmet Emin Ceylan
Med. Sci. 2019, 7(2), 21; https://doi.org/10.3390/medsci7020021 - 31 Jan 2019
Cited by 10 | Viewed by 5719
Abstract
The search for rational treatment of neuropsychiatric disorders began with the discovery of chlorpromazine in 1951 and continues to evolve. Day by day, new details of the intestinal microbiota–brain axis are coming to light. As the role of microbiota in the etiopathogenesis of [...] Read more.
The search for rational treatment of neuropsychiatric disorders began with the discovery of chlorpromazine in 1951 and continues to evolve. Day by day, new details of the intestinal microbiota–brain axis are coming to light. As the role of microbiota in the etiopathogenesis of neuropsychiatric disorders is more clearly understood, microbiota-based (or as we propose, “fecomodulation”) treatment options are increasingly discussed in the context of treatment. Although their history dates back to ancient times, the importance of psychobiotics and fecal microbiota transplantation (FMT) has only recently been recognized. Despite there being few preclinical and clinical studies, the evidence gathered to this point suggests that consideration of the microbiome in the treatment of neuropsychiatric disorders represents an area of significant therapeutic potential. It is increasingly hoped that such treatment options will be more reliable in terms of their side effects, cost, and ease of implementation. However, there remains much to be researched. Questions will be answered through germ-free animal experiments and randomized controlled trials. In this article, the therapeutic potential of microbiota-based options in the treatment of neuropsychiatric disorders is discussed in light of recent research. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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15 pages, 293 KiB  
Review
Microbiota in the Gastrointestinal Tract
by Walburga Dieterich, Monic Schink and Yurdagül Zopf
Med. Sci. 2018, 6(4), 116; https://doi.org/10.3390/medsci6040116 - 14 Dec 2018
Cited by 134 | Viewed by 9024
Abstract
Gut microbiota are permanent residents of humans with the highest concentrations being found in human colon. Humans get the first contact with bacteria at delivery, and microbiota are subject of permanent change during the life. The individual microbiota pattern is highly variable and [...] Read more.
Gut microbiota are permanent residents of humans with the highest concentrations being found in human colon. Humans get the first contact with bacteria at delivery, and microbiota are subject of permanent change during the life. The individual microbiota pattern is highly variable and varying environmental conditions, e.g., diets, antigen exposure, infections, or medication, as well as genetics, age, or hygiene factors, strongly influence the bacterial community. A fine interaction between the host and microbiota determines the outcome of health or disease. The gut immune system is constantly challenged to distinguish between commensal non-invasive bacteria and potential pathogens. Goblet cells produce mucins that prevent most gut bacteria from penetrating through intestinal epithelial barrier, and Paneth cells are the main supplier of anti-microbial defensins. Gut epithelial and immune cells recognize bacteria via surface markers and they initiate an adequate immune answer. A dysbiosis is noticed in several diseases, but the crucial role in pathogenesis has to be proven. Prebiotics or probiotics are discussed as valuable tools to preserve or restore a healthy gut community. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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13 pages, 477 KiB  
Review
Dietary Effects on Microbiota—New Trends with Gluten-Free or Paleo Diet
by Yurdagül Zopf, Dejan Reljic and Walburga Dieterich
Med. Sci. 2018, 6(4), 92; https://doi.org/10.3390/medsci6040092 - 18 Oct 2018
Cited by 18 | Viewed by 13692
Abstract
A well-balanced diet is the basis for a healthy life. Both the western diet and special diets can have a relevant impact on the microbiome and promote the development of various diseases. There has been an increase in food-related disorders in recent years, [...] Read more.
A well-balanced diet is the basis for a healthy life. Both the western diet and special diets can have a relevant impact on the microbiome and promote the development of various diseases. There has been an increase in food-related disorders in recent years, largely associated with dramatic changes in food consumption trends and main nutrients. A major response to food intolerances has been the adoption of new dietary trends involving the reduction or exclusion of specific food ingredients. Especially gluten-containing, but also gluten-free cereals are in the cross-fire. Supporters of the gluten-free diet argue that gluten triggers inflammation and related diseases, while followers of the Paleo diet drastically impeach all cereals as dangerous for human health. To date, no controlled studies support or reject a positive health effect of a gluten-free or cereal-free diet. Future large-scale studies need to evaluate the effect of gluten-containing and gluten-free cereals and the various diets on human health, inflammatory parameters, clinical symptoms, and the gut microbiota (including the bacteria, fungi, and viruses). Dietary-associated changes in compositional and functional microbiota traits should be correlated with the health status for the future development of dietary recommendations and potential clinical interventions. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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10 pages, 970 KiB  
Review
Microbiota and Phage Therapy: Future Challenges in Medicine
by Armelle Paule, Domenico Frezza and Marvin Edeas
Med. Sci. 2018, 6(4), 86; https://doi.org/10.3390/medsci6040086 - 05 Oct 2018
Cited by 52 | Viewed by 9088
Abstract
An imbalance of bacterial quantity and quality of gut microbiota has been linked to several pathologies. New strategies of microbiota manipulation have been developed such as fecal microbiota transplantation (FMT); the use of pre/probiotics; an appropriate diet; and phage therapy. The presence of [...] Read more.
An imbalance of bacterial quantity and quality of gut microbiota has been linked to several pathologies. New strategies of microbiota manipulation have been developed such as fecal microbiota transplantation (FMT); the use of pre/probiotics; an appropriate diet; and phage therapy. The presence of bacteriophages has been largely underestimated and their presence is a relevant component for the microbiome equilibrium. As a promising treatment, phage therapy has been extensively used in Eastern Europe to reduce pathogenic bacteria and has arisen as a new method to modulate microbiota diversity. Phages have been selected and “trained” to infect a wide spectrum of bacteria or tailored to infect specific antibiotic resistant bacteria present in patients. The new development of genetically modified phages may be an efficient tool to treat the gut microbiota dysbiosis associated with different pathologies and increased production of bacterial metabolites and subsequently decrease systemic low-grade chronic inflammation associated with chronic diseases. Microbiota quality and mitochondria dynamics can be remodulated and manipulated by phages to restore the equilibrium and homeostasis of the system. Our aim is to highlight the great interest for phages not only to eliminate and control pathogenic bacterial infection but also in the near future to modulate the microbiota by adding new functions to selected bacteria species and rebalance the dynamic among phages and bacteria. The challenge for the medicine of tomorrow is to re-think and redesign strategies differently and far from our traditional thinking. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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9 pages, 515 KiB  
Review
Gut–Liver Axis: How Do Gut Bacteria Influence the Liver?
by Peter Christopher Konturek, Igor Alexander Harsch, Kathrin Konturek, Monic Schink, Thomas Konturek, Markus F. Neurath and Yurdaguel Zopf
Med. Sci. 2018, 6(3), 79; https://doi.org/10.3390/medsci6030079 - 17 Sep 2018
Cited by 104 | Viewed by 8744
Abstract
Chronic liver diseases are a major cause of morbidity and mortality worldwide. Recently, gut dysbiosis was identified as an important factor in the pathogenesis of liver diseases. The relationship between gut microbiota and the liver is still not well understood; however, dysfunction of [...] Read more.
Chronic liver diseases are a major cause of morbidity and mortality worldwide. Recently, gut dysbiosis was identified as an important factor in the pathogenesis of liver diseases. The relationship between gut microbiota and the liver is still not well understood; however, dysfunction of the gut mucosal barrier (“leaky gut”) and increased bacterial translocation into the liver via the gut–liver axis probably play crucial roles in liver disease development and progression. The liver is an important immunological organ, and, after exposure to gut-derived bacteria via portal circulation, it responds with activation of the innate and adaptive immune system, leading to hepatic injury. A better understanding of the pathophysiological links among gut dysbiosis, the integrity of the gut barrier, and the hepatic immune response to gut-derived factors is essential for the development of new therapies to treat chronic liver diseases. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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20 pages, 816 KiB  
Review
The Gut Microbiome in Multiple Sclerosis: A Potential Therapeutic Avenue
by Trevor O. Kirby and Javier Ochoa-Repáraz
Med. Sci. 2018, 6(3), 69; https://doi.org/10.3390/medsci6030069 - 24 Aug 2018
Cited by 75 | Viewed by 13758
Abstract
Recently, there has been a substantial increase in the number of studies focused upon connecting the gut microbiome with cases of central nervous system (CNS) autoimmunity. Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the CNS. Recent experimental and clinical evidence suggests [...] Read more.
Recently, there has been a substantial increase in the number of studies focused upon connecting the gut microbiome with cases of central nervous system (CNS) autoimmunity. Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the CNS. Recent experimental and clinical evidence suggests the presence of microbial imbalances in the gut of MS sufferers. The gut microbiome is defined as the summation of all the microbial entities as well as their genes, proteins, and metabolic products in a given space and time. Studies show the MS gut microbiome as having general alterations in specific taxa, some associated with the promotion of inflammatory cytokines and overall inflammation. In conjunction with these findings, experimental models of the disease have reported that T regulatory (Treg) cells have deficits in their function as a result of the aberrant gut microbiota composition. The findings suggest that the interactions between the host and the microbiota are reciprocal, although more extensive work is required to confirm this. Moreover, evidence indicates that changes in microbiota composition may result in imbalances that could result in disease, with the gut as a potential novel therapeutic avenue. By understanding the biological effects of aberrant gut microbiome composition, it is possible to contemplate current therapeutic options and their efficacy. Ultimately, more research is necessary in this field, but targeting the gut microbiota may lead to the development of novel therapeutic strategies. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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Graphical abstract

23 pages, 1158 KiB  
Review
Gut Microbiota and Mucosal Immunity in the Neonate
by Majda Dzidic, Alba Boix-Amorós, Marta Selma-Royo, Alex Mira and Maria Carmen Collado
Med. Sci. 2018, 6(3), 56; https://doi.org/10.3390/medsci6030056 - 17 Jul 2018
Cited by 84 | Viewed by 12718
Abstract
Gut microbiota colonization is a complex, dynamic, and step-wise process that is in constant development during the first years of life. This microbial settlement occurs in parallel with the maturation of the immune system, and alterations during this period, due to environmental and [...] Read more.
Gut microbiota colonization is a complex, dynamic, and step-wise process that is in constant development during the first years of life. This microbial settlement occurs in parallel with the maturation of the immune system, and alterations during this period, due to environmental and host factors, are considered to be potential determinants of health-outcomes later in life. Given that host–microbe interactions are mediated by the immune system response, it is important to understand the close relationship between immunity and the microbiota during birth, lactation, and early infancy. This work summarizes the evidence to date on early gut microbiota colonization, and how it influences the maturation of the infant immune system and health during the first 1000 days of life. This review will also address the influence of perinatal antibiotic intake and the importance of delivery mode and breastfeeding for an appropriate development of gut immunity. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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15 pages, 1944 KiB  
Review
The Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease
by Sanjoy Roychowdhury, Praveen Conjeevaram Selvakumar and Gail A.M. Cresci
Med. Sci. 2018, 6(2), 47; https://doi.org/10.3390/medsci6020047 - 05 Jun 2018
Cited by 14 | Viewed by 5282
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with prevalence increasing in parallel with the rising incidence in obesity. Believed to be a “multiple-hit” disease, several factors contribute to NAFLD initiation and progression. Of these, the gut microbiome [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with prevalence increasing in parallel with the rising incidence in obesity. Believed to be a “multiple-hit” disease, several factors contribute to NAFLD initiation and progression. Of these, the gut microbiome is gaining interest as a significant factor in NAFLD prevalence. In this paper, we provide an in-depth review of the progression of NAFLD, discussing the mechanistic modes of hepatocyte injury and the potential role for manipulation of the gut microbiome as a therapeutic strategy in the prevention and treatment of NAFLD. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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28 pages, 1352 KiB  
Review
The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into “Old” Diseases
by Igor Alexander Harsch and Peter Christopher Konturek
Med. Sci. 2018, 6(2), 32; https://doi.org/10.3390/medsci6020032 - 17 Apr 2018
Cited by 115 | Viewed by 21152
Abstract
The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. [...] Read more.
The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids—especially butyrate—of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and “metabolic endotoxinemia” as well as “metabolic infection.” This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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