The gut microbiome: Relationships with disease and opportunities for therapy.

Over the past decade, our view of human-associated microbes has expanded beyond that of a few species toward an appreciation of the diverse and niche-specialized microbial communities that develop in the human host with chronological age. The largest reservoir of microbes exists in the distal gastrointestinal tract, both in the lumen, where microbes facilitate primary and secondary metabolism, and on mucosal surfaces, where they interact with host immune cell populations. While local microbial-driven immunomodulation in the gut is well described, more recent studies have demonstrated a role for the gut microbiome in influencing remote organs and mucosal and hematopoietic immune function. Unsurprisingly, therefore, perturbation to the composition and function of the gut microbiota has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological, cardiovascular, and respiratory illnesses. Considerable effort is currently focused on understanding the natural history of microbiome development in humans in the context of health outcomes, in parallel with improving our knowledge of microbiome-host molecular interactions. These efforts ultimately aim to develop effective approaches to rehabilitate perturbed human microbial ecosystems as a means to restore health or prevent disease. This review details the role of the gut microbiome in modulating host health with a focus on immunomodulation and discusses strategies for manipulating the gut microbiome for the management or prevention of chronic inflammatory conditions

Plants and plant products in treatment of ulcerative colitis

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2022, Universidade de Lisboa, Faculdade de Farmácia.A doença inflamatória intestinal (DII) é uma das doenças graves que influenciam a saúde e a qualidade de vida de milhões de pessoas em todo o mundo. É dividida em duas principais doenças Crónicas: colite ulcerosa (CU) e doença de Crohn (DC). A etiologia da DII ainda não é conhecida. No entanto, diferentes estudos mostraram que esta é afetada por fatores imunológicos, genéticos e ambientais. Tanto a CU como a DC são caracterizadas por inflamação crónica do trato gastrointestinal. Na CU, a inflamação começa distalmente no reto e estende-se proximalmente ao cólon; a DC pode afetar todo o trato gastrointestinal, da boca ao ânus. Com foco na CU, o Canadá tem a maior incidência e prevalência, seguido pelos EUA, países escandinavos, Finlândia, Reino Unido e Austrália. A terapia convencional da CU consiste em aminossalicilatos, corticosteroides e imunomoduladores. Devido aos seus imensos efeitos adversos e elevado custo, essas opções terapêuticas não são suficientemente bem-sucedidas e levam ao insucesso do tratamento após algum tempo. Acredita-se que os produtos à base de plantas e plantas medicinais sejam uma importante alternativa para o tratamento desta condição. Este estudo tem como objetivo rever a literatura sobre plantas e produtos vegetais que podem desempenhar um papel no tratamento da colite ulcerosa. Inclui os últimos 20 anos, concentrando-se mais na literatura de 2010 a 2021. Foram publicados muitos estudos experimentais in vivo/vitro e ensaios clínicos de plantas de produtos vegetais. Apesar de alguns dos mecanismos de ação das plantas estudadas serem conhecidos. Ainda assim, plantas e produtos vegetais têm resultados significativos em casos de colite experimental ou de ensaios clínicos, cujo mecanismo de ação permanece desconhecido ou merece maiores especificações. O resultado desta revisão de literatura está organizado em três divisões principais: plantas e produtos vegetais que melhoram a colite experimental, algumas formulações à base de plantas e plantas e produtos vegetais em ensaios clínicos. Existem vários resultados e benefícios obtidos em cada uma dessas categorias. É de salientar a formulação à base de plantas KM1608, derivada de Zingiber officinale, Terminalia chebula e Aucklandia lappa. Esta formulação à base de plantas na dose de 600 mg/kg resultou em melhores parâmetros para muitos índices usados para avaliar a colite experimental induzida por TNBS em comparação com 5-ASA e prednisolona. Portanto, estudos futuros devem concentrar-se mais na terapia de múltiplos alvos, uma vez que apenas uma terapia alvo nestas doenças complexas não obteve sucesso. É necessário mais investimento na investigação neste campo para obter resultados satisfatórios para construir uma guideline de tratamento mais segura e bem sucedida para a colite ulcerosa.Inflammatory bowel disease (IBD) is one of the serious diseases influencing millions of people`s health and quality of life worldwide. It is divided into two main chronic diseases: ulcerative colitis (UC) and Crohn's disease (CD). The etiology of IBD is not known yet. However, different studies have shown that it's affected by immunological, genetic, and environmental factors. Both UC and CD are characterized by chronic inflammation of the gastrointestinal tract. In UC, inflammation starts distally in the rectum and extends proximally to the colon; the CD can affect the entire gastrointestinal tract from the mouth to the anus. Focusing on UC, Canada has the highest incidence and prevalence, followed by the USA, Scandinavian countries, Finland, the UK, and Australia. Conventional therapy of UC consists of aminosalicylates, corticosteroids, and immunomodulators. Due to their immense adverse effects and high cost, these therapeutical options are not successful enough and lead to a failure in treatment after some time. Medicinal plants and plants product is believed to be an important alternative to treat this condition. This study aims to review the literature on plants and plant products that can play a role in treating ulcerative colitis. It includes the last 20 years, concentrating more on literature from 2010 to 2021. Many published experimental studies in vivo/vitro and clinical trials of plants and plant products have been recorded. Despite some of the mechanisms of action of the plants studied are known. Still, plants and plant products have significant outcomes in experimental colitis or clinical trial cases, whose mechanism of action remains unknown or deserves further specifications. The finding of this literature review is organized into three main divisions: plants and plant products that ameliorate experimental colitis, some herbal formulations, and plants and plants products in clinical trials. There are various outcomes and benefits obtained in each of these categories. To be distinguished is KM1608 herbal formulation, derived from Zingiber officinale, Terminalia chebula, and Aucklandia lappa. This herbal formulation at a 600 mg/kg dose resulted in better parameters for many indices used to evaluate TNBS-induced experimental colitis compared with 5-ASA and prednisolone. Hence future studies should focus more on multiple target therapy since just one target therapy in these complex diseases has failed to succeed. Further investment in more research in this field is needed to obtain satisfactory results to build a safer and more successful treatment guideline for ulcerative colitis

Inflammatory bowel disease and complementary and alternative medicine - The perspectives of patients and healthcare professionals

Background: Inflammatory bowel disease (IBD) is a term that covers ulcerative colitis (UC) and Crohn’s disease (CD). The causes of IBD are unknown and the incidence is increasing. IBD is a lifelong disease with severe symptoms that affect daily life and Health Related Quality of Life (HRQOL). The medical treatment for IBD is complex and many patients suffer from side effects of medication. Complementary and Alternative Medicine (CAM) encompasses methods that are not a part of conventional healthcare and not generally provided by the Swedish healthcare system. The use of CAM is increasing, especially in chronic diseases. Aim: The overall aim of this thesis was to investigate the use of CAM in patients with IBD and to explore attitudes to and experiences of CAM in patients with IBD and healthcare professionals (HCPs). An additional aim was to investigate IBD patients’ worries and disease related concerns in relation to CAM use. Study I was a controlled cross-sectional and multicentre study. The study enrolled 648 patients with IBD from 12 IBD clinics in Sweden. The control group comprised 440 individuals selected from Statens Personadressregister (SPAR). Data were collected by means of questionnaire. The results revealed that 48.5% (n = 313) of the IBD patients had used some form of CAM in the past year, compared with 53.5% (n = 235) in the control group. The most common CAM methods used by IBD patients compared to the control group were massage 21,3% vs 31,4%, herbal remedies 18,7% vs 21,3%, relaxation 10,5% vs 11,6%, yoga 8% vs 9,6%, acupuncture 7,6% vs 8,9%, counselling 7,3% vs. 6,2 and chiropractic 5,4 vs 5,7%. Study II was an interview study in which HCPs were asked to describe their experiences and attitudes to CAM. The participants were 16 physicians and nurses who had worked with IBD patients for 1-42 years. The results demonstrated that IBD nurses and physicians had confidence in and a positive attitude to CAM, especially when used as a complement to conventional medicine. The participants were of the opinion that patients considered and tested various CAM methods. They stated that CAM has a role in healthcare, which indicates acceptance. However, attitudes that constituted an obstacle to CAM were also reported, such as lack of evidence. Some participants had a restrictive approach and considered CAM unnecessary, while a few were sceptical. Study III comprised interviews in which 15 IBD patients described their experiences of CAM both alone and in combination with conventional medical treatment. It was found that patients with IBD wished to be consulted and have a discussion about CAM. They felt disparaged and not taken seriously when they wanted to discuss CAM. HCPs need to be aware of this issue in order to meet and understand IBD patients’ needs. The IBD patients considered it easier to discuss CAM with nurses than with physicians, which underlines IBD nurses’ important role in communicating with and monitoring IBD patients’ use of CAM. HCPs should be aware that IBD patients consider dietary changes an important CAM treatment. Study IV was a controlled, cross-sectional and multicentre study. Data from 12 IBD clinics in Sweden were collected by means of questionnaires. A total of 645 IBD patients were enrolled and asked to answer two questionnaires; a studyspecifik questionnaire concerning CAM use, disease and demographic data and the Rating Form of Inflammatory Bowel Disease Patients’ Concerns (RFIPC) questionnaire. The RFIPC consists of 25 questions to which patients respond by indicating how worried they are about a particular aspect on a VAS scale from 0-100. The questionnaire also contains an open question “Is there anything more that concerns you?”, which the patients answer in their own words. Of the participants, 313 used CAM and expressed more concerns in 15 of the 25 RFIPC items compared to patients who did not do so/non-users. CAM use was related to younger age and female gender. The open question revealed that IBD had a major impact on everyday life and that IBD patients’ worry concerned: The family and self, the burden of disease and associated factors. Conclusion: Patients with IBD used CAM in an attempt to achieve improvement and wellbeing. They considered dietary changes an important CAM treatment with positive effects on their condition. HCPs attitudes to CAM were mainly positive, although a problematic aspect was lack of knowledge and evidence. The HCPs acknowledged their need for education and respected the patients’ decision to use CAM. However, patients with IBD reported reluctance on the part of HCPs, being treated in a disparaging manner and not taken seriously when wishing to discuss CAM. They wanted to be asked about their CAM use and start a dialogue, but found it easier to discuss CAM treatment with nurses than physicians. Patients using CAM generally had more disease-related concerns compared to those who did not do so. IBD affects the whole of everyday life, especially the family and the self

Chronic Intestinal Disorders in Humans and Pets: Current Management and the Potential of Nutraceutical Antioxidants as Alternatives

Chronic intestinal disorders (CID) are characterized by persistent, or recurrent gastrointestinal (GI) signs present for at least three weeks. In human medicine, inflammatory bowel disease (IBD) is a group of chronic GI diseases and includes Crohn’s disease (CD) and ulcerative colitis (UC). On the other hand, the general term chronic enteropathies (CE) is preferred in veterinary medicine. Different therapeutic approaches to these diseases are used in both humans and pets. This review is focused on the use of traditional therapies and nutraceuticals with specific antioxidant properties, for the treatment of CID in humans and animal patients. There is strong evidence of the antioxidant properties of the nutraceuticals included in this review, but few studies report their use for treating CID in humans and none in animals. Despite this fact, the majority of the nutraceuticals described in the present article could be considered as promising alternatives for the regular treatment of CID in human and veterinary medicine

The Potential of Epigallocatechin-3-gallate (EGCG) as Complementary Medicine for the Treatment of Inflammatory Bowel Disease

Complementary and alternative medicine has the potential to enrich conventional therapy to improve the treatment of various diseases. Patients that suffer from inflammatory bowel disease, which requires a constant need for medication, have to deal with the adverse effects of repeated application. Natural products such as Epigallocatechin-3-gallate (EGCG) possess the potential to improve symptoms of inflammatory diseases. We investigated the efficacy of EGCG on an inflamed co-culture model simulating IBD and compared it to the efficacies of four commonly applied active pharmaceutical ingredients. EGCG (200 µg/mL) strongly stabilized the TEER value of the inflamed epithelial barrier to 165.7 ± 4.6% after 4 h. Moreover, the full barrier integrity was maintained even after 48 h. This corresponds to the immunosuppressant 6-Mercaptopurin and the biological drug Infliximab. The EGCG treatment significantly decreased the release of the pro-inflammatory cytokines IL-6 (to 0%) and IL-8 (to 14.2%), similar to the effect of the corticosteroid Prednisolone. Therefore, EGCG has a high potential to be deployed as complementary medicine in IBD. In future studies, the improvement of EGCG stability is a key factor in increasing the bioavailability in vivo and fully harnessing the health-improving effects of EGCG

Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice

Advances in understanding of health-promoting benefits of medicine and food homology using analysis of gut microbiota and metabolomics

The health-promoting benefits of medicine and food homology (MFH) are known for thousands of years in China. However, active compounds and biological mechanisms are unclear, greatly limiting clinical practice of MFH. The advent of gut microbiota analysis and metabolomics emerge as key tools to discover functional compounds, therapeutic targets, and mechanisms of benefits of MFH. Such studies hold great promise to promote and optimize functional efficacy and development of MFH-based products, for example, foods for daily dietary supplements or for special medical purposes. In this review, we summarized pharmacological effects of 109 species of MFH approved by the Health and Fitness Commission in 2015. Recent studies applying genome sequencing of gut microbiota and metabolomics to explain the activity of MFH in prevention and management of health consequences were extensively reviewed. We discussed the potentiality in future to decipher functional activities of MFH by applying metabolomics-based polypharmacokinetic strategy and multiomics technologies. The needs for personalized MFH recommendations and comprehensive databases have also been highlighted. This review emphasizes current achievements and challenges of the analysis of gut microbiota and metabolomics as a new avenue to understand MFH

BIOSENSING SYSTEMS FOR THE DETECTION OF BACTERIAL QUORUM SENSING MOLECULES: A TOOL FOR INVESTIGATING BACTERIA-RELATED DISORDERS AND FOOD SPOILAGE PREVENTION

Quorum sensing enables bacteria to communicate with bacteria of the same or different species, and to modulate their behavior in a cell-density dependent manner. Communication occurs by means of small quorum sensing signaling molecules (QSMs) whose concentration is proportional to the population size. When a QSM threshold concentration is reached, certain genes are expressed, thus allowing control of several processes, such as, virulence factor production, antibiotic production, and biofilm formation. Not only many pathogenic bacteria are known to produce QSMs, but also QSMs have been identified in some bacteria-related disorders. Therefore, quantitative detection of QSMs present in clinical samples may be a useful tool in the investigation and monitoring of bacteria-related diseases, thus prompting the use of QSMs as biomarkers of disease. Herein, we have developed and utilized whole-cell biosensing systems and protein based biosensing systems to detect QSMs in clinical samples, such as, saliva, stool, and bowel secretions. Additionally, since bacteria are responsible for food spoilage, we employed the developed biosensing systems to detect QSMs in food samples and demonstrated their applicability for early identification of food contamination. Furthermore, we have utilized these biosensing systems to screen antibacterial compounds employed for food preservation, namely, generally regarded as safe (GRAS) compounds, for their effect on quorum sensing

Natural Health Products, Modulation of Immune Function and Prevention of Chronic Diseases

The immune system is increasingly found to be involved in the development of several chronic illnesses, for which allopathic medicine has provided limited tools for treatment and especially prevention. In that context, it appears worthwhile to target the immune system in order to modulate the risk of certain chronic illnesses. Meanwhile, natural health products (NHPs) are generating renewed interest, particularly in the prevention and treatment of several chronic diseases. Over 20 scientists from fields related to immune function and NHPs were thus convened to establish the state of knowledge on these subjects and to explore future research directions. This review summarizes the result of discussions held during the symposium. It thus seeks to be thought provoking rather than to comprehensively cover such broad areas of research. Notably, a brief overview of the immune system is presented, including potentially useful targets and strategies to keep it in an equilibrated state, in order to prevent certain disorders. The pertinence and limitations of targeting the immune system to prevent chronic diseases is also discussed. The paper then discusses the usefulness and limitations of current experimental tools available to study the immune modulating effects of NHPs. Finally, a concise review of some of the most studied NHPs showing promising immunomodulatory activity is given, and avenues for future research are described