Change in intestinal alkaline phosphatase activity is a hallmark of antibiotic-induced intestinal dysbiosis

Dissanayake Wijesooriya Mudhiyanselage Nadeema,Chandanee Malavige Romesha,Lee Sang-Myeong,허정민,이영주 아세아·태평양축산학회 2023 Animal Bioscience Vol.36 No.9

Objective: Intestinal alkaline phosphatase (IAP) maintains intestinal homeostasis by detoxifying bacterial endotoxins and regulating gut microbiota, and lipid absorption. Antibiotics administered to animals can cause gut dysbiosis and barrier disruption affecting animal health. Therefore, the present study sought to investigate the role of IAP in the intestinal environment in dysbiosis. Methods: Young male mice aged 9 weeks were administered a high dose of antibiotics to induce dysbiosis. They were then sacrificed after 4 weeks to collect the serum and intestinal organs. The IAP activity in the ileum and the level of cytokines in the serum samples were measured. Quantitative real-time polymerase chain reaction analysis of RNA from the intestinal samples was performed using primers for tight junction proteins (TJPs) and proinflammatory cytokines. The relative intensity of IAP and toll-like receptor 4 (TLR4) in intestinal samples was evaluated by western blotting. Results: The IAP activity was significantly lower in the ileum samples of the dysbiosisinduced group compared to the control. The interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha concentrations were significantly higher in the ileum samples of the dysbiosis-induced group. The RNA expression levels of TJP2, claudin-3, and claudin-11 showed significantly lower values in the intestinal samples from the dysbiosis-induced mice. Results from western blotting revealed that the intensity of IAP expression was significantly lower in the ileum samples of the dysbiosis-induced group, while the intensity of TLR4 expression was significantly higher compared to that of the control group without dysbiosis. Conclusion: The IAP activity and relative mRNA expression of the TJPs decreased, while the levels of proinflammatory cytokines increased, which can affect intestinal integrity and the function of the intestinal epithelial cells. This suggests that IAP is involved in mediating the intestinal environment in dysbiosis induced by antibiotics and is an enzyme that can potentially be used to maintain the intestinal environment in animal health care.

장내 세균 불균형과 비만

김규남(Kyu-Nam Kim) 대한기능의학회 2020 Journal of Korean Institute for Functional Medicin Vol.3 No.2

According to recent research results, approximately 40 trillion bacteria exist in the human gut, and this gut microbiota interact with our body from birth and contribute to maintaining our health. In order to maintain healthy gut microbiota, there are dietary habits such as a low fat and a high fiber diet. The preference of a high fat or a low fiber diet, and antibiotic ingestion is the cause of the gut dysbiosis. Gut dysbiosis leads to decreased production of secondary bile acids, decreased production of short-chain fatty acids, and inflammation, which contributing to the onset of obesity. Therapeutic strategy using beneficial bacteria and non-absorbable antibiotics has been studied as a clinical approach for the treatment of gut dysbiosis, but this application did not cause clinically significant weight change. However, since the metabolic indicators related to obesity have improved, it is necessary to develop a therapeutic approach to gut dysbiosis in the treatment of obesity. In addition, there are not many studies on the analysis of intestinal bacteria at the species level or strain level related to intestinal bacterial imbalance, so further studies are needed to be conducted. Herein, the author reviews studies linking gut microbiome to obesity, as well as studies analyzing their associated mechanisms and treatments. 최근 연구 결과에 의하면 사람의 장내에는 40조에 가까운 균이 존재하며 이러한 장내 세균은 사람이 태어나면서부터 우리 몸과 상호작용을 하며 우리의 건강을 유지하는데 기여한다. 건강한 장내 세균을 유지하기 위해서는 저지방 식이와 고섬유질 식이 등의 식습관이 있는데 고지방 식이나 저섬유질 식이의 선호는 문 수준에서의 Firmicutes/Bacteroidetes 비율 증가의 특징을 가지는 장내 세균 불균형의 원인이 된다. 장내 세균 불균형은 이차성 담즙산의 생성 감소 및 짧은 사슬 지방산 생성 감소, 염증 발생을 초래하여 비만의 발병에 기여하게 된다. 장내 세균 불균형 치료를 위한 임상적 접근법으로 유익균과 비흡수성 항생제 치료가 연구되어 왔으나 임상적으로 의미 있는 체중 변화를 일으키지는 않았다. 그러나 비만과 관련 있는 대사 지표의 호전을 보였기에 비만 치료에 있어 장내 세균 불균형에 대한 치료적 접근 전략을 세울 필요가 있다. 또한 아직까진 장내 세균 불균형과 관련된 종 수준이나 strain 수준에서의 장내 세균 분석 연구들은 많지 않아 이와 관련된 연구가 더 이루어져야 할 것으로 보이며 미래에는 비만과 관련 있는 특이 장내 세균을 확인하여 비만 치료에 이용될 것으로 보인다.

The Use of Probiotics in Preterm Infants

박혜원 대한신생아학회 2022 Neonatal medicine Vol.29 No.2

Probiotics are live microorganisms that positively affect host health by altering the composition of the host microbiota. Gastrointestinal dysbiosis refers to adverse alterations of the intestinal flora and is associated with several diseases, including necrotizing enterocolitis, late-onset sepsis in preterm infants as well as atopic disease, colic, diabetes, and diarrhea in term infants. The risk factors for gastrointestinal dysbiosis are preterm birth, cesarean section delivery, and formula feeding, in contrast to term birth infants, vaginal delivery and breast milk feeding. Probiotics have been used to restore synbiosis in infants with gastrointestinal dysbiosis. Probiotics inhibit colonization of pathogenic bacteria in the gastrointestinal tract, thereby improving the barrier function of the gastrointestinal tract, and the immune function. In preterm infants, probiotics reduce mortality as well as rates of necrotizing enterocolitis and late-onset sepsis. The combined use of probiotics such as Lactobacillus and Bifidobacterium and the combination of probiotics with prebiotics yield better outcomes in the prevention of necrotizing enterocolitis than those achieved with a single pro- or prebiotic strain. However, the routine use of probiotics has been hindered by the lack of pharmaceutical-quality products, and a definite effect has yet to be demonstrated in preterm infants with a birth weight <1,000 g. Therefore, to reduce the risk of necrotizing enterocolitis in preterm infants, probiotics should be provided along with breast milk and other strategies aimed at preventing gastrointestinal dysbiosis.

Microbial Modulation in Inflammatory Bowel Diseases

Yu Jongwook,Cheon Jae Hee 대한면역학회 2022 Immune Network Vol.22 No.6

Gut dysbiosis is one of prominent features in inflammatory bowel diseases (IBDs) which are of an unknown etiology. Although the cause-and-effect relationship between IBD and gut dysbiosis remains to be elucidated, one area of research has focused on the management of IBD by modulating and correcting gut dysbiosis. The use of antibiotics, probiotics either with or without prebiotics, and fecal microbiota transplantation from healthy donors are representative methods for modulating the intestinal microbiota ecosystem. The gut microbiota is not a simple assembly of bacteria, fungi, and viruses, but a complex organ-like community system composed of numerous kinds of microorganisms. Thus, studies on specific changes in the gut microbiota depending on which treatment option is applied are very limited. Here, we review previous studies on microbial modulation as a therapeutic option for IBD and its significance in the pathogenesis of IBD.

Drosophila as a model for intestinal dysbiosis and chronic inflammatory diseases

Lee, K.A.,Lee, W.J. Pergamon Press ; Elsevier Science 2014 DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY Vol.42 No.1

The association between deregulated intestinal microbial consortia and host diseases has been recognized since the birth of microbiology over a century ago. Intestinal dysbiosis refers to a state where living metazoans harbor harmful intestinal microflora. However, there is still an issue of whether causality arises from the host or the microbe because it is unclear whether deregulation of the gut microbiota community is the consequence or cause of the host disease. Recent studies using Drosophila and its simple microbiota have provided a valuable model system for dissecting the molecular mechanisms of intestinal dysbiosis. In this review, we examine recent exciting observations in Drosophila gut-microbiota interactions, particularly the links among the host immune genotype, the microbial community structure, and the host inflammatory phenotype. Future genetic analyses using Drosophila model system will provide a valuable outcome for understanding the evolutionarily conserved mechanisms that underlie intestinal dysbiosis and chronic inflammatory diseases.

The Effect of Curcumin on the Gut-Brain Axis: Therapeutic Implications

Ayesheh Enayati,Aida Soghi,Alexandra E Butler,Manfredi Rizzo,Amirhossein Sahebkar 대한소화기 기능성질환∙운동학회 2023 Journal of Neurogastroenterology and Motility (JNM Vol.29 No.4

The gut-brain axis describes the bidirectional communication between the gut, the enteric nervous system, and the central nervous system. The gut-brain axis has attracted increasing attention owing to its regulatory effect on dysbiosis and a wide range of related diseases. Several types of nutrients, such as curcumin, have been proposed as regulators of the dysbiotic state, and preclinical experiments have suggested that curcumin is not only beneficial but also safe. This review focuses on the interplay between curcumin and the gut microbiota. Moreover, it provides a comprehensive review of the crosstalk between the gut-brain axis and disease, whilst also discussing curcumin-mediated gut-brain axis-dependent and -independent signaling about modulation of gut microbiota dysbiosis. This will help to define the utility of curcumin as a novel therapeutic agent to regulate intestinal microflora dysbiosis.

Virechana karma (therapeutic purgation) in the restoration of gut microbiota concerning Amavata (RA): A scientific exposition

Godbole, Amrit,Sweta, Sweta,Abhinav, Abhinav,Singh, O.P. Cellmed Orthocellular Medicine and Pharmaceutical 2021 셀메드 (CellMed) Vol.11 No.1

Background: Amavata is a disease that occurs as a result of the error of metabolism. Poor dietary habits and faulty Dincharya (daily regimen) and ritucharya (seasonal regimen) leading to deranged metabolism and Agni (metabolic fire) which results in the formation of Ama(undigested product of metabolism). When Amaconceals with Vata(subtle energy associated with movement) and circulates in the body under the influence of Vyana Vayu (omnipresent air)it clogs the srotasas (microchannels) and initiates the inflammatory cascade. Amavata is commonly correlated with rheumatoid arthritis (RA) while other forms of auto-immune disorders can also be included in Amavata.Dysbiosis of the gut microbiota (GM) has been connected to the onset of diverse autoimmune diseases. In this study, it was hypothesized that Panchakarma (bio-purificatory methods) based intervention such as Virechana Karma (therapeutic purgation) may influence microbiota. Materials and Methods: Various Ayurvedic literature were reviewed for the etiopathogenesis of Amavata. Different databases were searched with research papers related to Gut Dysbiosis and autoimmunity and management of RA. A connecting link between Intestinal Dysbiosis with the autoimmune mechanisms was established and it was also found that the bowel cleansing introduced a change to the GM. Conclusion: It was concluded that Virechana karma is effective in gut flora Dysbiosis. This study aims to correlate the ancient Ayurvedic principles related to Agni Bala(metabolic energy) and biopurificatory treatment modalities like Virechana karma (therapeutic purgation)with the modern concept of gut microbiota and its role in the pathogenesis of various autoimmune disorders such as rheumatoid arthritis. The article creates an understanding about principles of Ayurveda and its rationality in today's scientific world and thereby opens newer vistas of research in therapeutics from Ayurveda, which may be helpful in the management of various immune-mediated Diseases through Ayurveda.

장내 세균 불균형에 대한 혈청 지표들

김규남(Kyu-Nam Kim) 대한기능의학회 2023 Journal of Korean Institute for Functional Medicin Vol.6 No.1

현재까지 장내 세균 불균형을 임상적으로 평가하는 방법인 수소/메탄 호기 검사나 대변을 이용한 차세대 염기서열법은 일차의료를 담당하는 의료인이 채택하기가 쉽지 않다. 따라서 비록 많은 연구가 이루어지지 않았지만 이론적으로 설명 가능한 기전을 바탕으로 일차의료에서 어렵지 않게 장내 세균 불균형을 의심할 수 있는 혈액지표에 대해 이번 종설에 논의하였고 이들 지표에는 혈중 총 빌리루빈, 간기능 수치, 비타민 B-12, 피브리노겐, 페리틴 등이 있었다. 총 빌리루빈은 산화스트레스에 대한 방어 기전으로 상승하며 간기능은 장누수와 관련해서 상승하고 비타민 B-12는 장내 세균 불균형에 의한 생성된 대사물로 증가하고 피브리노겐과 페리틴은 장내 세균 불균형에 의한 내독소의 증가가 미세염증을 일으켜 상승할 것으로 생각되고 있다. 아직까지 이들 관계에 대해서는 거의 연구가 이루어지지 않았기에 기능의학적 관점을 가진 연구진들이 추후 더 관심을 갖고 진료 및 연구를 통해 이에 대한 관계를 밝혀야 할 것이다. Until now, it is not easy for medical personnel in charge of primary care to adopt hydrogen/methane breath test or next-generation sequencing using feces, which are methods for clinically evaluating gut dysbiosis. Therefore, although not many studies have been conducted, this review discusses serum indicators that can easily suspect gut dysbiosis in primary care based on theoretically explainable mechanisms, and these indicators include serum total bilirubin, liver function level, vitamin B-12, fibrinogen, and ferritin. Total bilirubin rises as a defense mechanism against oxidative stress, liver function rises in relation to leaky gut, and vitamin B-12 increases as a metabolite produced by intestinal bacterial imbalance. Fibrinogen and ferritin are thought to rise due to microinflammation caused by an increase in endotoxin caused by gut dysbiosis. So far, few studies have been conducted on these relationships, so researchers with a functional medicine perspective should be more interested in treatment and research to reveal the relationship in the future.

Pathogenic role of the gut microbiota in gastrointestinal diseases

( Hiroko Nagao Kitamoto ),( Sho Kitamoto ),( Peter Kuffa ),( Nobuhiko Kamada ) 대한장연구학회 2016 Intestinal Research Vol.14 No.2

The gastrointestinal (GI) tract is colonized by a dense community of commensal microorganisms referred to as the gut microbiota. The gut microbiota and the host have co-evolved, and they engage in a myriad of immunogenic and metabolic interactions. The gut microbiota contributes to the maintenance of host health. However, when healthy microbial structure is perturbed, a condition termed dysbiosis, the altered gut microbiota can trigger the development of various GI diseases including inflammatory bowel disease, colon cancer, celiac disease, and irritable bowel syndrome. There is a growing body of evidence suggesting that multiple intrinsic and extrinsic factors, such as genetic variations, diet, stress, and medication, can dramatically affect the balance of the gut microbiota. Therefore, these factors regulate the development and progression of GI diseases by inducing dysbiosis. Herein, we will review the recent advances in the field, focusing on the mechanisms through which intrinsic and extrinsic factors induce dysbiosis and the role a dysbiotic microbiota plays in the pathogenesis of GI diseases. (Intest Res 2016;14:127-138)

5-Aminosalicylic acid intolerance is associated with a risk of adverse clinical outcomes and dysbiosis in patients with ulcerative colitis

( Shinta Mizuno ),( Keiko Ono ),( Yohei Mikami ),( Makoto Naganuma ),( Tomohiro Fukuda ),( Kazuhiro Minami ),( Tatsuhiro Masaoka ),( Soichiro Terada ),( Takeshi Yoshida ),( Keiichiro Saigusa ),( Norim 대한장연구학회 2020 Intestinal Research Vol.18 No.1

Background/Aims: 5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota. Methods: We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC. Results: Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P<0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P<0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P<0.05). Conclusions: In patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC. (Intest Res 2020;18:69-78)