高雄醫學大學圖書館 |

Role of Probiotics and Gut Microbiota in Modulating Host Immunity and Disease /

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Role of Probiotics and Gut Microbiota in Modulating Host Immunity and Disease // Tsz Ching Kwong.
作者:	Kwong, Tsz Ching,
面頁冊數:	1 electronic resource (217 pages)
附註:	Source: Dissertations Abstracts International, Volume: 86-08, Section: B.
提要註:	The gut microbiome significantly influences mammalian host health, impacting metabolism, immune function, and behaviour. The comprehensive analysis presented in the doctoral dissertation entitled "Role of Probiotics and Gut Microbiota in Modulating Host Immunity and Disease" delves into the intricate relationship between probiotics, gut microbiota, and diabetes mellitus, with emphasis on the modulation of the host's immune system by next-generation probiotics as a novel vaccination strategy.Given the similarities between domestic dogs (Canis familiaris) and humans, the study begins by defining the gut microbiome of healthy domestic dogs and that of those suffering from canine diabetes mellitus (CDM) as a comparative disease model. Utilizing targeted 16S rRNA sequencing and comprehensive bioinformatic analysis of faecal samples, this research represents a pioneering effort to define the 'healthy' canine gut microbiome profile and reveal significant differences in the gut microbial landscape of diabetic canines at the genera, species, functional, and network levels. In particular, a three-fold increase in pathogenic Clostridioides difficile abundance was observed in diabetic dogs, suggesting a link to gastrointestinal complications affecting CDM management. Additionally, a marked shift towards carbohydrate degradation pathways in diabetic dogs indicates gut microbiome adaptation to disease progression. These findings established a foundation for canine gut microbiome research and inform future microbiome-targeted disease management strategies.The second part of the thesis examines the influence of probiotics on host health. A six-week daily probiotic intervention in db/db mice revealed a trend towards reduced HOMA-IR index and HbA1c level, suggesting a potential beneficial effect on alleviating diabetic symptoms, although further research is needed to achieve statistical significance. The safety of probiotic administration was confirmed through key organ damage assessments. Post-intervention analysis demonstrated alterations in overall microbial composition and diversity, evidenced by changes in relative abundance and significant differences in alpha and beta diversity measures. Notably, the enrichment of beneficial bacteria, such as Bacteroides spp., and the downregulation of carbohydrate degradation pathways indicated an improvement in gut balance following probiotic supplementation. Comparisons to reference 'healthy' gut microbiome in canines showed noticeable similarities between the healthy and probiotic-supplemented groups, providing additional evidence of gut microbiota restoration and underscoring the importance of maintaining gut microbiota balance for better disease management.In recent years, the integration of traditional probiotics with modern biotechnology has revolutionized the fields of therapeutics and vaccination, resulting in the development of next-generation probiotics. These probiotics share similarities with live biotherapeutic products and are becoming more popular as a new way to deliver pharmaceuticals for therapeutic use or immunomodulation. The global COVID-19 pandemic, which is caused by the SARS-CoV-2 virus, continues to impact the world due to the rapid emergence of new and highly contagious variants. While vaccination remains the most effective strategy for preventing viral infections, some countries are still facing challenges in accessing vaccines due to limitations in the manufacturing and transportation of the doses. Consequently, there is a pressing need to develop a low-cost, user-friendly, and safe vaccination approach to address this issue. Genetically modified microorganisms, particularly next-generation probiotics, are increasingly recognized as promising vehicles for delivering bioactive molecules through oral and mucosal routes. In this proof-of-concept study, probiotic Lactobacillus casei has been selected as the oral vaccine candidate based on its natural immunoadjuvant properties as well as the ability to withstand the acidic gastric environment, to express antigens of SARS-CoV-2 Omicron variant B.1.1.529 with B-cell and T-cell epitopes. This newly developed vaccine, namely OMGVac, has been proven to generate a significantly higher IgG (titre of 3,526 U/mL) in response to the Omicron variant B.1.1.529 spike protein in the golden Syrian hamster model, when compared to control groups. No adverse effects were identified during the study, and the overall safety was assessed by examining the physiology and histopathology of major organs harvested. The study provided solid evidence on the use of a recombinant probiotic as a live delivery vector for triggering systemic immunity, which shed light on the future development of next-generation vaccines against emerging infectious diseases.The thesis concludes that microbiome and probiotics, both traditional and next-generation, hold substantial potential as therapeutic and immunomodulatory tools for diseases involving immune dysregulation, such as diabetes mellitus and COVID-19. However, it emphasises the necessity for rigorous, standardized clinical trials to validate their efficacy and safety. The thesis evaluates the use of probiotics in modulating gut dysbiosis, highlighting the challenges in interpreting the results due to variability in probiotic strains, dosage, and study design. Finally, the study suggests future research directions, including the development of next-generation probiotics-based therapies based on an individual's gut microbiota composition.
Contained By:	Dissertations Abstracts International86-08B.
標題:	Animal sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31869170
ISBN:	9798304975391

Role of Probiotics and Gut Microbiota in Modulating Host Immunity and Disease /
Kwong, Tsz Ching,

Role of Probiotics and Gut Microbiota in Modulating Host Immunity and Disease /Tsz Ching Kwong. - 1 electronic resource (217 pages)

Source: Dissertations Abstracts International, Volume: 86-08, Section: B.

The gut microbiome significantly influences mammalian host health, impacting metabolism, immune function, and behaviour. The comprehensive analysis presented in the doctoral dissertation entitled "Role of Probiotics and Gut Microbiota in Modulating Host Immunity and Disease" delves into the intricate relationship between probiotics, gut microbiota, and diabetes mellitus, with emphasis on the modulation of the host's immune system by next-generation probiotics as a novel vaccination strategy.Given the similarities between domestic dogs (Canis familiaris) and humans, the study begins by defining the gut microbiome of healthy domestic dogs and that of those suffering from canine diabetes mellitus (CDM) as a comparative disease model. Utilizing targeted 16S rRNA sequencing and comprehensive bioinformatic analysis of faecal samples, this research represents a pioneering effort to define the 'healthy' canine gut microbiome profile and reveal significant differences in the gut microbial landscape of diabetic canines at the genera, species, functional, and network levels. In particular, a three-fold increase in pathogenic Clostridioides difficile abundance was observed in diabetic dogs, suggesting a link to gastrointestinal complications affecting CDM management. Additionally, a marked shift towards carbohydrate degradation pathways in diabetic dogs indicates gut microbiome adaptation to disease progression. These findings established a foundation for canine gut microbiome research and inform future microbiome-targeted disease management strategies.The second part of the thesis examines the influence of probiotics on host health. A six-week daily probiotic intervention in db/db mice revealed a trend towards reduced HOMA-IR index and HbA1c level, suggesting a potential beneficial effect on alleviating diabetic symptoms, although further research is needed to achieve statistical significance. The safety of probiotic administration was confirmed through key organ damage assessments. Post-intervention analysis demonstrated alterations in overall microbial composition and diversity, evidenced by changes in relative abundance and significant differences in alpha and beta diversity measures. Notably, the enrichment of beneficial bacteria, such as Bacteroides spp., and the downregulation of carbohydrate degradation pathways indicated an improvement in gut balance following probiotic supplementation. Comparisons to reference 'healthy' gut microbiome in canines showed noticeable similarities between the healthy and probiotic-supplemented groups, providing additional evidence of gut microbiota restoration and underscoring the importance of maintaining gut microbiota balance for better disease management.In recent years, the integration of traditional probiotics with modern biotechnology has revolutionized the fields of therapeutics and vaccination, resulting in the development of next-generation probiotics. These probiotics share similarities with live biotherapeutic products and are becoming more popular as a new way to deliver pharmaceuticals for therapeutic use or immunomodulation. The global COVID-19 pandemic, which is caused by the SARS-CoV-2 virus, continues to impact the world due to the rapid emergence of new and highly contagious variants. While vaccination remains the most effective strategy for preventing viral infections, some countries are still facing challenges in accessing vaccines due to limitations in the manufacturing and transportation of the doses. Consequently, there is a pressing need to develop a low-cost, user-friendly, and safe vaccination approach to address this issue. Genetically modified microorganisms, particularly next-generation probiotics, are increasingly recognized as promising vehicles for delivering bioactive molecules through oral and mucosal routes. In this proof-of-concept study, probiotic Lactobacillus casei has been selected as the oral vaccine candidate based on its natural immunoadjuvant properties as well as the ability to withstand the acidic gastric environment, to express antigens of SARS-CoV-2 Omicron variant B.1.1.529 with B-cell and T-cell epitopes. This newly developed vaccine, namely OMGVac, has been proven to generate a significantly higher IgG (titre of 3,526 U/mL) in response to the Omicron variant B.1.1.529 spike protein in the golden Syrian hamster model, when compared to control groups. No adverse effects were identified during the study, and the overall safety was assessed by examining the physiology and histopathology of major organs harvested. The study provided solid evidence on the use of a recombinant probiotic as a live delivery vector for triggering systemic immunity, which shed light on the future development of next-generation vaccines against emerging infectious diseases.The thesis concludes that microbiome and probiotics, both traditional and next-generation, hold substantial potential as therapeutic and immunomodulatory tools for diseases involving immune dysregulation, such as diabetes mellitus and COVID-19. However, it emphasises the necessity for rigorous, standardized clinical trials to validate their efficacy and safety. The thesis evaluates the use of probiotics in modulating gut dysbiosis, highlighting the challenges in interpreting the results due to variability in probiotic strains, dosage, and study design. Finally, the study suggests future research directions, including the development of next-generation probiotics-based therapies based on an individual's gut microbiota composition.

English

ISBN: 9798304975391Subjects--Topical Terms:

524030
Animal sciences.
Subjects--Index Terms:

Disease management

Role of Probiotics and Gut Microbiota in Modulating Host Immunity and Disease /
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500 $a Source: Dissertations Abstracts International, Volume: 86-08, Section: B.
500 $a Advisors: Wa, Kwan Yiu; Shum, Sau Wun Committee members: Tsui, Kwok Wing; Siu, Kit Hang Gilman.
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520 $a The gut microbiome significantly influences mammalian host health, impacting metabolism, immune function, and behaviour. The comprehensive analysis presented in the doctoral dissertation entitled "Role of Probiotics and Gut Microbiota in Modulating Host Immunity and Disease" delves into the intricate relationship between probiotics, gut microbiota, and diabetes mellitus, with emphasis on the modulation of the host's immune system by next-generation probiotics as a novel vaccination strategy.Given the similarities between domestic dogs (Canis familiaris) and humans, the study begins by defining the gut microbiome of healthy domestic dogs and that of those suffering from canine diabetes mellitus (CDM) as a comparative disease model. Utilizing targeted 16S rRNA sequencing and comprehensive bioinformatic analysis of faecal samples, this research represents a pioneering effort to define the 'healthy' canine gut microbiome profile and reveal significant differences in the gut microbial landscape of diabetic canines at the genera, species, functional, and network levels. In particular, a three-fold increase in pathogenic Clostridioides difficile abundance was observed in diabetic dogs, suggesting a link to gastrointestinal complications affecting CDM management. Additionally, a marked shift towards carbohydrate degradation pathways in diabetic dogs indicates gut microbiome adaptation to disease progression. These findings established a foundation for canine gut microbiome research and inform future microbiome-targeted disease management strategies.The second part of the thesis examines the influence of probiotics on host health. A six-week daily probiotic intervention in db/db mice revealed a trend towards reduced HOMA-IR index and HbA1c level, suggesting a potential beneficial effect on alleviating diabetic symptoms, although further research is needed to achieve statistical significance. The safety of probiotic administration was confirmed through key organ damage assessments. Post-intervention analysis demonstrated alterations in overall microbial composition and diversity, evidenced by changes in relative abundance and significant differences in alpha and beta diversity measures. Notably, the enrichment of beneficial bacteria, such as Bacteroides spp., and the downregulation of carbohydrate degradation pathways indicated an improvement in gut balance following probiotic supplementation. Comparisons to reference 'healthy' gut microbiome in canines showed noticeable similarities between the healthy and probiotic-supplemented groups, providing additional evidence of gut microbiota restoration and underscoring the importance of maintaining gut microbiota balance for better disease management.In recent years, the integration of traditional probiotics with modern biotechnology has revolutionized the fields of therapeutics and vaccination, resulting in the development of next-generation probiotics. These probiotics share similarities with live biotherapeutic products and are becoming more popular as a new way to deliver pharmaceuticals for therapeutic use or immunomodulation. The global COVID-19 pandemic, which is caused by the SARS-CoV-2 virus, continues to impact the world due to the rapid emergence of new and highly contagious variants. While vaccination remains the most effective strategy for preventing viral infections, some countries are still facing challenges in accessing vaccines due to limitations in the manufacturing and transportation of the doses. Consequently, there is a pressing need to develop a low-cost, user-friendly, and safe vaccination approach to address this issue. Genetically modified microorganisms, particularly next-generation probiotics, are increasingly recognized as promising vehicles for delivering bioactive molecules through oral and mucosal routes. In this proof-of-concept study, probiotic Lactobacillus casei has been selected as the oral vaccine candidate based on its natural immunoadjuvant properties as well as the ability to withstand the acidic gastric environment, to express antigens of SARS-CoV-2 Omicron variant B.1.1.529 with B-cell and T-cell epitopes. This newly developed vaccine, namely OMGVac, has been proven to generate a significantly higher IgG (titre of 3,526 U/mL) in response to the Omicron variant B.1.1.529 spike protein in the golden Syrian hamster model, when compared to control groups. No adverse effects were identified during the study, and the overall safety was assessed by examining the physiology and histopathology of major organs harvested. The study provided solid evidence on the use of a recombinant probiotic as a live delivery vector for triggering systemic immunity, which shed light on the future development of next-generation vaccines against emerging infectious diseases.The thesis concludes that microbiome and probiotics, both traditional and next-generation, hold substantial potential as therapeutic and immunomodulatory tools for diseases involving immune dysregulation, such as diabetes mellitus and COVID-19. However, it emphasises the necessity for rigorous, standardized clinical trials to validate their efficacy and safety. The thesis evaluates the use of probiotics in modulating gut dysbiosis, highlighting the challenges in interpreting the results due to variability in probiotic strains, dosage, and study design. Finally, the study suggests future research directions, including the development of next-generation probiotics-based therapies based on an individual's gut microbiota composition.
520 $a 腸道微生物群顯著影響哺乳動物宿主的健康,包括代謝、免疫功能和行為。博士論文《益生菌和腸道微生物在調節宿主免疫和疾病中的作用》的綜合分析並深入探討益生菌、腸道微生物和糖尿病之間的複雜關係,重點在於利用次世代益生菌作為新型疫苗策略來調節宿主免疫系統。鑑於家犬(Canis familiaris)和人類之間的相似性,是次研究收集家犬糞便樣本進行靶向16S rRNA次世代測序和綜合生物信息學分析。研究首先定義"健康"犬腸道微生物群,並以此為對照和患有犬糖尿病 (CDM)的家犬的腸道微生物群作出深入比較。研究結果顯示,糖尿病犬的腸道微生物群在屬、種、功能和網絡層面存在顯著差異。特別是糖尿病犬中致病性困難梭菌(Clostridioides difficile)的豐度增加了三倍, 暗示與影響 CDM管理的腸胃併發症有關。此外,腸道微生物群會因應糖尿病進展作出適應變化,顯著趨向利用更多碳水化合物降解途徑。這些發現為犬腸道微生物群研究奠定了基礎,並為未來針對微生物群的疾病管理策略提供了參考。論文的第二部分研究了益生菌對宿主健康的影響。對db/db 小鼠進行為期六週的每日乾酪乳桿菌益生菌干預,結果顯示HOMA-IR 指數和 HbAlc 水平均有下降趨勢,暗示益生菌在緩解糖尿病症狀方面的潛在有益效果,但需要進一步研究以達到統計顯著性。通過對主要器官損傷的評估,確認了益生菌使用的安全性。干預後分析顯示,整體微生物組成和多樣性發生了變化,表現在相對豐度的改變和多樣性與多樣性測量上的顯著差異。值得注意的是,益生菌補充後,有益細菌(如擬桿菌屬) 豐度增加,碳水化合物降解途徑的下調表明腸道平衡得到改善。與參考 "健康"犬腸道微生物群的比較顯示,健康組和益生菌補充組之間有顯著相似性,進一步證明了腸道微生物群的恢復,強調了維持腸道微生物群平衡對更好疾病管理的重要性。近年來,傳統益生菌和現代生物技術的結合已經革新了治療和疫苗接種領域,促成了次世代益生菌的發展。由於新型冠狀病毒(SARS-CoV-2)引起的全球COVID-19大流行仍在快速傳播及變異,新型高度傳染性變異株更持續對世界造成了重大的影響。雖然疫苗接種仍然是預防病毒感染最有效的策略,但由於疫苗的生產和運輸存在限制,一些國家仍然面臨著疫苗接種的挑戰。因此,開發一種低成本、易於使用和安全的疫苗接種方法確實有迫切需要。基因改造微生物,特別是次世代益生菌,是目前被認為是最有前途的口服和黏膜傳遞生物活性分子載體。在本次概念驗證研究中,一株具有天然免疫佐劑以及在酸性胃環境中耐受性質的益生菌菌株被選為口服疫苗候選者。透過基因轉殖技術,使該菌株表達 SARS-CoV-2 Omicron 變異株B.1.1.529的B細胞和T細胞抗原表位。這種新開發的疫苗(命名為OMGVac),在金黃敘利亞倉鼠模型中證明能夠產生3526U/mL的平均IgG濃度,並針對 Omicron 變種 B.1.1.529 的刺突蛋白產生系統性免疫反應。研究期間未發現任何不良反應,並通過檢查主要器官的生理和組織病理學評估了總體安全性。該研究提供了使用次世代益生菌作為活體傳遞載體以觸發全身免疫的堅實證據,為未來開發針對新興傳染病的次世代疫苗提供了啟示。論文總結道,傳統和次世代益生菌在免疫失調相關疾病(如糖尿病和COVID-19)的治療和免疫調節工具中具有巨大潛力。然而,它強調了需要更嚴格和標準化的臨床試驗來驗證其有效性和安全性。論文評估了益生菌作為治療劑的使用,突出了由於益生菌菌株、劑量和研究設計的變異性對調節及平衡腸道健康的重要作用。最後,研究提出了未來的研究方向,包括基於個體腸道微生物群組成的次世代益生菌療法的開發。.
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