Simotang Alleviates the Gastrointestinal Side Effects of Chemotherapy by Altering Gut Microbiota

( Lijing Deng ),( Xingyi Zhou ),( Zhifang Lan ),( Kairui Tang ),( Xiaoxu Zhu ),( Xiaowei Mo ),( Zongyao Zhao ),( Zhiqiang Zhao ),( Mansi Wu ) 한국미생물생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.4

Simotang oral liquid (SMT) is a traditional Chinese medicine (TCM) consisting of four natural plants and is used to alleviate gastrointestinal side effects after chemotherapy and functional dyspepsia (FD). However, the mechanism by which SMT helps cure these gastrointestinal diseases is still unknown. Here, we discovered that SMT could alleviate gastrointestinal side effects after chemotherapy by altering gut microbiota. C57BL/6J mice were treated with cisplatin (DDP) and SMT, and biological samples were collected. Pathological changes in the small intestine were observed, and the intestinal injury score was assessed. The expression levels of the inflammatory factors IL-1β and IL-6 and the adhesive factors Occludin and ZO-1 in mouse blood or small intestine tissue were also detected. Moreover, the gut microbiota was analyzed by high-throughput sequencing of 16S rRNA amplicons. SMT was found to effectively reduce gastrointestinal mucositis after DDP injection, which lowered inflammation and tightened the intestinal epithelial cells. Gut microbiota analysis showed that the abundance of the anti-inflammatory microbiota was downregulated and that the inflammatory microbiota was upregulated in DDP-treated mice. SMT upregulated antiinflammatory and anticancer microbiota abundance, while the inflammatory microbiota was downregulated. An antibiotic cocktail (ABX) was also used to delete mice gut microbiota to test the importance of gut microbiota, and we found that SMT could not alleviate gastrointestinal mucositis after DDP injection, showing that gut microbiota might be an important mediator of SMT treatment. Our study provides evidence that SMT might moderate gastrointestinal mucositis after chemotherapy by altering gut microbiota.

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)

미생물 균총이 위장관암과 항암제에 미치는 영향

김사랑(Sa-Rang Kim),이정민(Jung Min Lee) 한국생명과학회 2022 생명과학회지 Vol.32 No.5

인간 미생물 균총은 장, 구강, 피부와 같이 체내외 다양한 부위에 존재하는 박테리아, 균류, 바이러스 등을 포함하는 미생물 집단이다. 16s ribosomal RNA에 대한 대사체 분석 및 차세대 염기서열 분석기술의 개발과 함께, 살아있는 유기체 내에 존재하는 미생물 균총에 대한 많은 연구가 진행되었다. 이에 따라, 미생물 균총이 숙주의 대사 및 면역과정과 복잡하게 연관되어 있음이 확인되었다. 공생균(commensal microbiota)이라 불리는 미생물 균총의 특정 박테리아가 필수 영양소를 생성하거나 다른 병원성 미생물로부터 숙주를 보호하여 긍정적으로 영향을 미치고 있는 반면, 비정상적인 미생물 균총의 조성을 의미하는 미생물 균총의 불균형(dysbiosis)에 의해 체내 항상성 유지를 방해하여 다양한 종류의 질병을 발생시키기도 한다. 최근, 미생물 균총 중에서도 구강과 장내 존재하는 박테리아가 위장관암의 발암과정과 항암제의 치료효과에 상당한 영향을 미치고 있음이 여러 논문을 통해 보고되고 있다. 미생물 균총-암-면역계 사이의 복잡한 연관성과 미생물 균총 기반 발암 메커니즘에 대한 규명은 암에 대한 이해와 새로운 항암제 개발에 중요한 단서를 제공할 것으로 기대된다. 본 리뷰는 미생물 균총의 박테리아가 위장관암과 항암제에 어떤 영향을 미치고 있는지에 대해 초점을 맞추고 있는 논문들을 요약하고 있으며, 나아가 기존 항암제의 치료효과를 개선하기 위해 복합제로써 미생물 균총의 잠재력과 도전과제에 대해 논의한다. Human microbiota is a community of microorganisms, including bacteria, fungi, and viruses, that inhabit various locations of the body, such as the gut, oral, and skin. Along with the development of metabolomic analysis and next-generation sequencing techniques for 16S ribosomal RNA, it has become possible to analyze the population for subtypes of microbiota, and with these techniques, it has been demonstrated that bacterial microbiota are involved in the metabolic and immunological processes of the hosts. While specific bacteria of microbiota, called commensal bacteria, positively affect hosts by producing essential nutrients and protecting hosts against other pathogenic microorganisms, dysbiosis, an abnormal microbiota composition, disrupts homeostasis and thereby has a detrimental effect on the development and progression of various types of diseases. Recently, several studies have reported that oral and gut bacteria of microbiota are involved in the carcinogenesis of gastrointestinal tumors and the therapeutic effects of anticancer therapy, such as radiation, chemotherapy, targeted therapy, and immunotherapy. Studying the complex relationships (bacterial microbiota-cancer-immunity) and microbiota-related carcinogenic mechanisms can provide important clues for understanding cancer and developing new cancer treatments. This review provides a summary of current studies focused on how bacterial microbiota affect gastrointestinal cancer and anticancer therapy and discusses compelling possibilities for using microbiota as a combinatorial therapy to improve the therapeutic effects of existing anticancer treatments.

COVID-19 and the Human Gut Microbiome: An Under-Recognized Association

Abu Fahad Abbasi,Aleksandra Marinkovic,Stephanie Prakash,Adekunle Sanyaolu,Stella Smith 전남대학교 의과학연구소 2022 전남의대학술지 Vol.58 No.3

Coronavirus disease 2019 (COVID-19) is an infectious disease with a wide range of respiratory and extrapulmonary symptoms, as well as gastrointestinal symptoms. Despite recent research linking gut microbiota to infectious diseases like influenza, minimal information is known about the gut microbiota’s function in COVID-19 pathogenesis. Studies suggest that dysbiosis of the gut microbiota and gut barrier dysfunction may play a role in COVID-19 pathogenesis by disrupting host immune homeostasis. Regardless of whether patients had taken medication or disease severity, the gut microbiota composition was significantly altered in COVID-19 patients compared to non-COVID-19 individuals. Several gut commensals with recognized immunomodulatory potential, such as Faecalibacterium prausnitzii, Eubacterium rectale, and bifidobacteria, were underrepresented in patients and remained low in samples taken several weeks after disease resolution. Furthermore, even with disease resolution, dysbiosis in the gut microbiota may contribute to chronic symptoms, underscoring the need to learn more about how gut microbes play a role in inflammation and COVID-19.

Revolutionizing gut health: exploring the role of gut microbiota and the potential of microbiome-based therapies in lower gastrointestinal diseases

박용은,김재현 고신대학교(의대) 고신대학교 의과대학 학술지 2023 고신대학교 의과대학 학술지 Vol.38 No.2

The gut microbiota comprises a collection of microorganisms residing in the human digestive system, including bacteria, viruses, and fungi. These microbes have critical roles in food breakdown, immune system regulation, and the production of essential nutrients. Several lower gastrointestinal (GI) diseases, including inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, have been associated with dysbiosis, which refers to an imbalance in the gut microbiota. Additionally, the gut microbiome and its microbial compounds affect disease development and the host’s immune response. Alterations in the gut-brain axis microbiome are also implicated in lower GI diseases. Therefore, microbiome-based therapies that regulate the gut microbiota (e.g., fecal microbiota transplantation and probiotics) are essential for the prevention and treatment of these diseases. This review aims to highlight the significance of gut microbiota and microbiome-based therapies in managing lower GI diseases.

Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders

( Rajan Singh ),( Hannah Zogg ),( Lai Wei ),( Allison Bartlett ),( Uday C Ghoshal ),( Singh Rajender ),( Seungil Ro ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.1

Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. Studies are warranted to elucidate the cellular and molecular pathways underlying gut microbiota-host crosstalk and for the development of a powerful platform for future therapeutic approaches. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders. (J Neurogastroenterol Motil 2021;27:19-34)

Sex Differences in Gut Microbiota

김용성,Tatsuya Unno,Byung-Yong Kim,Mi-Sung Park 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.1

Humans carry numerous symbiotic microorganisms in their body, most of which are present in the gut. Although recent technological advances have produced extensive research data on gut microbiota, there are various confounding factors (e.g., diet, race, medications) to consider. Sex is one of the important variables affecting the gut microbiota, but the association has not yet been sufficiently investigated. Although the results are inconsistent, several animal and human studies have shown sex differences in gut microbiota. Herein, we review these studies to discuss the sex-dependent differences as well as the possible mechanisms involved.

— Invited Review — Assessment of the gastrointestinal microbiota using 16S ribosomal RNA gene amplicon sequencing in ruminant nutrition

김민석 아세아·태평양축산학회 2023 Animal Bioscience Vol.36 No.2

The gastrointestinal (GI) tract of ruminants contains diverse microbes that ferment various feeds ingested by animals to produce various fermentation products, such as volatile fatty acids. Fermentation products can affect animal performance, health, and well-being. Within the GI microbes, the ruminal microbes are highly diverse, greatly contribute to fermentation, and are the most important in ruminant nutrition. Although traditional cultivation methods provided knowledge of the metabolism of GI microbes, most of the GI microbes could not be cultured on standard culture media. By contrast, amplicon sequencing of 16S rRNA genes can be used to detect unculturable microbes. Using this approach, ruminant nutritionists and microbiologists have conducted a plethora of nutritional studies, many including dietary interventions, to improve fermentation efficiency and nutrient utilization, which has greatly expanded knowledge of the GI microbiota. This review addresses the GI content sampling method, 16S rRNA gene amplicon sequencing, and bioinformatics analysis and then discusses recent studies on the various factors, such as diet, breed, gender, animal performance, and heat stress, that influence the GI microbiota and thereby ruminant nutrition.

Prebiotic Effect of Fructooligosaccharide in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME® Model)

Katia Sivieri,Martha L. Villarreal Morales,Susana M.I. Saad,Maria A. Tallarico Adorno,Isabel Kimiko Sakamoto,Elizeu A. Rossi 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.8

Maintaining ‘‘gut health’’ is a goal for scientists throughout the world. Therefore, microbiota management models for testing probiotics, prebiotics, and synbiotics have been developed. The SHIME model was used to study the effect of fructooligosaccharide (FOS) on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 weeks using a culture medium. This stabilization period was followed by a 2-week control period during which the microbiota was monitored. The microbiota was then subjected to a 4-week treatment period by adding 5 g/day-1 FOS to vessel one (the ‘‘stomach’’ compartment). Plate counts, Denaturing Gradient Gel Electrophoresis (DGGE), short-chain fatty acid (SCFA), and ammonium analyses were used to observe the influence of FOS treatment in simulated colon compartments. A significant increase (P < .01) in the Lactobacillus spp. and Bifidobacterium spp. populations was observed during the treatment period. The DGGE obtained showed the overall microbial community was changed in the ascending colon compartment of the SHIME reactor. FOS induced increase of the SCFA concentration (P < .05) during the treatment period, mainly due to significant increased levels of acetic and butyric acids. However, ammonium concentrations increased during the same period (P < .01). This study indicates the usefulness of in vitro methods that simulate the colon region as part of research towards the improvement of human health.

Associations of physical activity with gut microbiota in pre-adolescent children

( Sara Santarossa ),( Alexandra R. Sitarik ),( Christine Cole Johnson ),( Jia Li ),( Susan V. Lynch ),( Dennis R. Ownby ),( Alex Ramirez ),( Germaine Lm. Yong ),( Andrea E. Cassidy-bushrow ) 한국운동영양학회 2021 Physical Activity and Nutrition (Phys Act Nutr) Vol.25 No.4

[Purpose] To determine whether physical activity (PA), primarily the recommended 60 minutes of moderate-to-vigorous PA, is associated with gut bacterial microbiota in 10-year-old children. [Methods] The Block Physical Activity Screener, which provides minutes/day PA variables, was used to determine whether the child met the PA recommendations. 16S rRNA sequencing was performed on stool samples from the children to profile the composition of their gut bacterial microbiota. Differences in alpha diversity metrics (richness, Pielou’s evenness, and Faith’s phylogenetic diversity) by PA were determined using linear regression, whereas beta diversity (unweighted and weighted UniFrac) relationships were assessed using PERMANOVA. Taxon relative abundance differentials were determined using DESeq2. [Results] The analytic sample included 321 children with both PA and 16S rRNA sequencing data (mean age [SD] =10.2 [0.8] years; 54.2% male; 62.9% African American), where 189 (58.9%) met the PA recommendations. After adjusting for covariates, meeting the PA recommendations as well as minutes/ day PA variables were not significantly associated with gut richness, evenness, or diversity (p ≥ 0.19). However, meeting the PA recommendations (weighted UniFrac R² = 0.014, p = 0.001) was significantly associated with distinct gut bacterial composition. These compositional differences were partly characterized by increased abundance of Megamonas and Anaerovorax as well as specific Christensenellaceae_R-7_group taxa in children with higher PA. [Conclusion] Children who met the recommendations of PA had altered gut microbiota compositions. Whether this translates to a reduced risk of obesity or associated metabolic diseases is still unclear.