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Article: Nurturing by nutrition: On the future of gut microbiota management strategies for autoimmune disease.

Larsen, Olaf F A

2023 Volume 9, Page(s) 1107016

Abstract: The incidence of autoimmune disease continues to rise, which urges for new prevention and treatment modalities. The composition of the gut microbiota is associated with both susceptibility and progression of disease. Nutrition significantly shapes the ... ...

Abstract	The incidence of autoimmune disease continues to rise, which urges for new prevention and treatment modalities. The composition of the gut microbiota is associated with both susceptibility and progression of disease. Nutrition significantly shapes the gut microbial composition, and poses as such a modality for both prevention and treatment/adjuvant therapy. At very young age, nutritional intervention targeting the gut microbiota is still possible within a one-size-fits all regime, accompanied by a relatively high effect size. As ageing results in higher interindividual variation induced by cumulative exposome factors, a more personalized approach is needed, having a higher effect size than that of current nutritional intervention. As such, supplementation of microbial consortia consisting of keystone taxa and microbial guilds that are involved in the pathophysiology seem a promising direction to lower the burden of autoimmune disease.
Language	English
Publishing date	2023-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2022.1107016
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Clinical research with probiotics as an indicator of global valorization since the year 2000.

Wiegers, Cato / van Beek, Eveline H T / Larsen, Olaf F A

Frontiers in microbiology

2023 Volume 14, Page(s) 1323920

Abstract: Probiotics are becoming increasingly popular due to their potential health benefits. With this rise in popularity and demand as indicated by ever-growing market prospects, it seems evident that innovation and valorization are on the rise as well. However, ...

Abstract	Probiotics are becoming increasingly popular due to their potential health benefits. With this rise in popularity and demand as indicated by ever-growing market prospects, it seems evident that innovation and valorization are on the rise as well. However, an increasing body of literature shows that innovation is stagnating, which may be detrimental to the exploitation of the benefits of probiotics, for example the development of alternative therapies to manage the increasing prevalence of metabolic and autoimmune disorders. To this end, this study investigated global clinical trials that have been executed since the year 2000 as a first indicator of the status of probiotic valorization. The cumulative number of clinical trials has indeed increased significantly from 0 at the start of the century up to 2,517 registered trials in 2023. However, in Asia, Europe, and North America, the continents with the highest numbers of clinical trials, stagnating or declining trends have been found. In these locations, most clinical trials were funded by non-industry sponsors and targeting probiotic supplements or undefined products. Considering the overall stagnation in clinical trials and viewing these trends in the context of developments in local markets and regulations, the global valorization of probiotics appears to slow down. This could impact the transition from academic research to the development of products that are beneficial and accessible for consumers, either to maintain a healthy lifestyle or to treat medical conditions.
Language	English
Publishing date	2023-12-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1323920
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Probiotics for the Management of Infectious Diseases: Reviewing the State of the Art.

Wiegers, Cato / van de Burgwal, Linda H M / Larsen, Olaf F A

Frontiers in microbiology

2022 Volume 13, Page(s) 877142

Abstract: This review aims to provide insight into the potential of probiotics as a clinical modality targeted at infectious diseases by creating a comprehensive overview of the state of the art of research and development efforts as shown by patents and clinical ... ...

Abstract	This review aims to provide insight into the potential of probiotics as a clinical modality targeted at infectious diseases by creating a comprehensive overview of the state of the art of research and development efforts as shown by patents and clinical trials of the past 20 years. Data were retrieved from patent and clinical trial databases to reflect the long- and short-term developments of probiotics research. The data were analyzed to extract information on the total number of patents and trials for each indication, application date and location, and applicant/sponsor type. A total of 80 infectious diseases were investigated, precipitating in 789 patents and 602 clinical trials for 67 indications studied as targets of probiotics. An increasing trend was seen for the number of patents and clinical trials that were applied for since 1999 with the highest number of patents and clinical trials targeted to digestive tract, respiratory, and urogenital indications. Overall, research demonstrated a substantial interest in probiotics targeting infectious diseases, which was in line with reported unmet needs and global probiotics sales estimates. However, the declining rate of translation from patents to clinical trials indicates that there are some barriers obstructing the research process.
Language	English
Publishing date	2022-04-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.877142
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Article: Reviewing the state of the art of probiotics as clinical modalities for brain-gut-microbiota axis associated disorders.

Wiegers, Cato / Veerman, Mariët A / Brummer, Robert Jan / Larsen, Olaf F A

Frontiers in microbiology

2022 Volume 13, Page(s) 1053958

Abstract: The rise in prevalence of mental and neurological disorders is causing a high burden on society, however adequate interventions are not always available. The brain-gut-microbiota axis (BGMA) may provide a new angle for the development of clinical ... ...

Abstract	The rise in prevalence of mental and neurological disorders is causing a high burden on society, however adequate interventions are not always available. The brain-gut-microbiota axis (BGMA) may provide a new angle for the development of clinical modalities. Due to the intricate bi-directional signaling between the brain and the gut, it may be helpful to look into interventions that target the gut, such as probiotics. Therefore, this review aimed to investigate the state of the art of probiotics and their potential as clinical modalities for BGMA-associated indications by gaining insight into patents and clinical trials that have been applied for and executed since 1999. A total of 565 patents and 390 clinical trials were found, focusing on probiotic applications for 83 indications. Since the start of the 21st century, the highest numbers of patents and clinical trials were related to primary neuropsychological, affective (depression, anxiety) and cognitive disorders, neurodegenerative and/or inflammatory brain disorders (Alzheimer's disease, Parkinson's disease, amongst others), and gastrointestinal disorders (irritable bowel syndrome). The locations where the most patents and clinical trials were registered included China, the United States, and Iran. From 1999 to ~2013 a slight growth could be seen in the numbers of patents and clinical trials, followed by an almost exponential growth from ~2013 onwards. Overall, the developments of the state of the art were in accordance with previous research, however it appeared that clinical trials showed a slightly slower growth compared to patents, which may have implications for the future implementation of probiotics as clinical modalities for BGMA-associated indications.
Language	English
Publishing date	2022-11-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.1053958
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: On the Verge of a Catastrophic Collapse? The Need for a Multi-Ecosystem Approach to Microbiome Studies.

Larsen, Olaf F A / van de Burgwal, Linda H M

Frontiers in microbiology

2021 Volume 12, Page(s) 784797

Abstract: While the COVID-19 pandemic has led to increased focus on pathogenic microbes that cross the animal-human species barrier, calls to include non-pathogenic interactions in our perspective on public health are gaining traction in the academic community. ... ...

Abstract	While the COVID-19 pandemic has led to increased focus on pathogenic microbes that cross the animal-human species barrier, calls to include non-pathogenic interactions in our perspective on public health are gaining traction in the academic community. Over generations, the diversity of the human gut microbiota is being challenged by external perturbations and reduced acquisition of symbiotic species throughout life. When such reduced diversity concerns not only the microbial species, but also the higher taxonomic levels and even the guild level, adequate compensation for possible losses may be lacking. Shifts from a high-abundance to a low-abundance state, known as a tipping point, may result in simultaneous shifts in covarying taxa and ultimately to a catastrophic collapse in which the ecosystem abruptly and possibly irreversibly shifts to an alternative state. Here, we propose that co-occurrence patterns within and between microbial communities across human, animal, soil, water, and other environmental domains should be studied in light of such critical transitions. Improved mechanistic understanding of factors that shape structure and function is needed to understand whether interventions can sustainably remodel disease-prone microbiota compositions to robust and resilient healthy microbiota. Prerequisites for a rational approach are a better understanding of the microbial interaction network, both within and inter-domain, as well as the identification of early warning signs for a catastrophic collapse, warranting a timely response for intervention. We should not forget that mutualism and pathogenicity are two sides of the same coin. Building upon the planetary health concept, we argue that microbiome research should include system level approaches to conserve ecosystem resilience. HIGHLIGHTS 1. Non-pathogenic interactions between ecosystems play a key role in maintaining health. 2. The human gut microbiome may be on the verge of a catastrophic collapse. 3. Research should identify keystone taxa and guilds that interconnect different domains. 4. We should not forget that mutualism and pathogenicity are two sides of the same coin.
Language	English
Publishing date	2021-12-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2021.784797
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The mechanistic link between health and gut microbiota diversity.

Larsen, Olaf F A / Claassen, Eric

Scientific reports

2018 Volume 8, Issue 1, Page(s) 2183

Abstract: Although numerous reports link a decreased diversity of the gut microbiota to a declined health status, to date no mechanistic motivation for this exists. Here, we show by applying first principles basic graph theory on small networks that higher ... ...

Abstract	Although numerous reports link a decreased diversity of the gut microbiota to a declined health status, to date no mechanistic motivation for this exists. Here, we show by applying first principles basic graph theory on small networks that higher diversity within such a network indeed leads to more efficient systems and redundancy. Our results quantitatively support earlier hypothetical considerations on gut microbiota richness with respect to these parameters. Our simulations show that higher species diversity leads to higher resilience within small microbiological ecosystems, like being present in the gut microbiota. This notion should provide an ingredient when developing new interventional strategies within the domain of microbiota management.
MeSH term(s)	Biodiversity ; Computer Simulation ; Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/microbiology ; Health Status ; Humans ; Microbiota
Language	English
Publishing date	2018-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-20141-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The Gut Microbiota: Master of Puppets Connecting the Epidemiology of Infectious, Autoimmune, and Metabolic Disease.

Larsen, Olaf F A / van der Grint, Maike / Wiegers, Cato / van de Burgwal, Linda H M

Frontiers in microbiology

2022 Volume 13, Page(s) 902106

Abstract: Infectious, autoimmune, and metabolic diseases put an enormous pressure on both quality of life and the economy. For all three disease types, it is known that the quality of the gut microbiota composition is correlated to both onset and progression of ... ...

Abstract	Infectious, autoimmune, and metabolic diseases put an enormous pressure on both quality of life and the economy. For all three disease types, it is known that the quality of the gut microbiota composition is correlated to both onset and progression of disease. Hence, maintaining eubiosis and preventing gradual irreversible loss of beneficial microbes within the gut microbial ecosystem is of utmost importance. As such, the epidemiological trends of these disease types may serve as proxies for the integrity of the human gut microbiota. Here, we present incidence data covering the last decades for prototypical infectious diseases (tuberculosis and measles), autoimmune disorders (type-1 diabetes and multiple sclerosis), and the prevalence of metabolic syndrome. Our findings reveal that vaccination efforts correlate with relatively low levels of archetypal infectious disease incidence. However, autoimmune and metabolic disorders are, together with the usage of antibiotics, steeply on the rise. These findings suggest that the status of the gut microbiota is persistently deteriorating, as reflected by the proxies. As such, the epidemiological trends shown here may serve as a starting point for a mechanistic understanding of the interplay between these different disease types that can be used for future prevention and mitigation strategies like targeted stimulation and suppletion of microorganisms by means of, e.g., fermented foods, prebiotics and probiotics.
Language	English
Publishing date	2022-04-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.902106
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Innovations in the veterinary intestinal health field: A patent landscape analysis.

Janse, Marga E M / Zinkweg, Dick B / Larsen, Olaf F A / van de Burgwal, Linda

One health (Amsterdam, Netherlands)

2022 Volume 15, Page(s) 100419

Abstract: In recent years it has become evident that a healthy intestinal microbiome is beneficial for the overall health of an individual. A healthy microbiome is diverse, increasing stability and resilience and strengthening the immune system. In addition, ... ...

Abstract	In recent years it has become evident that a healthy intestinal microbiome is beneficial for the overall health of an individual. A healthy microbiome is diverse, increasing stability and resilience and strengthening the immune system. In addition, healthy intestinal metabolisms have a beneficial effect on many physiological processes such as the brain function. Looking from the One Health perspective, which recognizes that health of humans is closely connected to the health of animals and environment, it is inherently beneficial to stimulate the health of animals for the well-being of humans. However, the intensive administration of antibiotics to livestock for prevention and cure of disease, and even stimulation of growth, disrupts a healthy microbiome. With the rapid increase of emerging zoonotic diseases, alternatives to the use of antimicrobial compounds are urgently necessary. This research analyses the development of alternatives for antibiotic use contributing to veterinary intestinal health through an in-depth patent analysis of inventions for fodder additives. In the period 1999-2020, 1269 unique patent families describing the use of probiotics, enzymes and prebiotics for swine, poultry and ruminants were identified. Innovation trends, geography, key applicants, and classification of patents were analysed. Asian industrial applicants applied for the majority of patents comprising the largest share of patents for probiotics and enzymes in combination with fodder for swine. Followed by North American and European industrial applications, applying for patents for probiotics in combination with fodder for poultry, swine, and ruminants. Overall, our results do not show a clear increase in innovations, suggesting that innovations in the use of probiotics and enzymes in animal feed appear to be stalling. While in the near future a combination of the use of antibiotics and alternatives is most likely to be implemented, the use of probiotics stands a good chance of replacing antibiotics in animal husbandry and limiting the adverse effects of antibiotic abuse.
Language	English
Publishing date	2022-07-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2834831-X
ISSN	2352-7714
ISSN	2352-7714
DOI	10.1016/j.onehlt.2022.100419
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The mechanistic link between health and gut microbiota diversity

Olaf F. A. Larsen / Eric Claassen

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 5

Abstract: Abstract Although numerous reports link a decreased diversity of the gut microbiota to a declined health status, to date no mechanistic motivation for this exists. Here, we show by applying first principles basic graph theory on small networks that ... ...

Abstract	Abstract Although numerous reports link a decreased diversity of the gut microbiota to a declined health status, to date no mechanistic motivation for this exists. Here, we show by applying first principles basic graph theory on small networks that higher diversity within such a network indeed leads to more efficient systems and redundancy. Our results quantitatively support earlier hypothetical considerations on gut microbiota richness with respect to these parameters. Our simulations show that higher species diversity leads to higher resilience within small microbiological ecosystems, like being present in the gut microbiota. This notion should provide an ingredient when developing new interventional strategies within the domain of microbiota management.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Innovations in the veterinary intestinal health field

Marga E.M. Janse / Dick B. Zinkweg / Olaf F.A. Larsen / Linda van de Burgwal

One Health, Vol 15, Iss , Pp 100419- (2022)

A patent landscape analysis

2022

Abstract	In recent years it has become evident that a healthy intestinal microbiome is beneficial for the overall health of an individual. A healthy microbiome is diverse, increasing stability and resilience and strengthening the immune system. In addition, healthy intestinal metabolisms have a beneficial effect on many physiological processes such as the brain function.Looking from the One Health perspective, which recognizes that health of humans is closely connected to the health of animals and environment, it is inherently beneficial to stimulate the health of animals for the well-being of humans. However, the intensive administration of antibiotics to livestock for prevention and cure of disease, and even stimulation of growth, disrupts a healthy microbiome. With the rapid increase of emerging zoonotic diseases, alternatives to the use of antimicrobial compounds are urgently necessary. This research analyses the development of alternatives for antibiotic use contributing to veterinary intestinal health through an in-depth patent analysis of inventions for fodder additives. In the period 1999–2020, 1269 unique patent families describing the use of probiotics, enzymes and prebiotics for swine, poultry and ruminants were identified. Innovation trends, geography, key applicants, and classification of patents were analysed.Asian industrial applicants applied for the majority of patents comprising the largest share of patents for probiotics and enzymes in combination with fodder for swine. Followed by North American and European industrial applications, applying for patents for probiotics in combination with fodder for poultry, swine, and ruminants. Overall, our results do not show a clear increase in innovations, suggesting that innovations in the use of probiotics and enzymes in animal feed appear to be stalling. While in the near future a combination of the use of antibiotics and alternatives is most likely to be implemented, the use of probiotics stands a good chance of replacing antibiotics in animal husbandry and ...
Keywords	Veterinary intestinal health ; Probiotics ; Enzymes ; Prebiotics ; Antibiotic use ; One health ; Medicine (General) ; R5-920
Subject code	360 ; 610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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