Intestinal Research

Review

Microbiota

Gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis: a review: Sung Wook Hwang, Min Kyu Kim, Mi-Na Kweon; Intest Res 2023;21(4):433-442. Published online August 29, 2023; DOI: https://doi.org/10.5217/ir.2023.00019

Immune checkpoint inhibitors have dramatically revolutionized the therapeutic landscape for patients with advanced malignancies. Recently, convincing evidence has shown meaningful influence of gut microbiome on human immune system. With the complex link between gut microbiome, host immunity and cancer, the variations in the gut microbiota may influence the efficacy of immune checkpoint inhibitors. Indeed, some bacterial species have been reported to be predictive for cancer outcome in patients treated with immune checkpoint inhibitors. Although immune checkpoint inhibitors are currently proven to be an effective anti-tumor treatment, they can induce a distinct form of toxicity, termed immune-related adverse events. Immune-related colitis is one of the common toxicities from immune checkpoint inhibitors, and it might preclude the cancer therapy in severe or refractory cases. The manipulation of gut microbiome by fecal microbiota transplantation or probiotics administration has been suggested as one of the methods to enhance anti-tumor effects and decrease the risk of immune-related colitis. Here we review the role of gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis to provide a new insight for better anti-cancer therapy.

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Date yogurt supplemented with Lactobacillus rhamnosus (ATCC 53103) encapsulated in wild sage (Salvia macrosiphon) mucilage and sodium alginate by extrusion: The survival and viability against the gastrointestinal condition, cold storage, heat, and salt wi
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Toxicity in the era of immune checkpoint inhibitor therapy
Synat Keam, Naimah Turner, Fernanda G. Kugeratski, Rene Rico, Jocelynn Colunga-Minutti, Rayansh Poojary, Sayan Alekseev, Anisha B. Patel, Yuanteng Jeff Li, Ajay Sheshadri, Monica E. Loghin, Karin Woodman, Ashley E. Aaroe, Sarah Hamidi, Priyanka Chandrasek
Frontiers in Immunology.2024;[Epub] CrossRef

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Original Article

Microbiota

Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease: Seung Yong Shin, Young Kim, Won-Seok Kim, Jung Min Moon, Kang-Moon Lee, Sung-Ae Jung, Hyesook Park, Eun Young Huh, Byung Chang Kim, Soo Chan Lee, Chang Hwan Choi, on behalf of the IBD Research Group of the Korean Association for the Study of Intestinal Diseases; Intest Res 2023;21(1):148-160. Published online June 14, 2022; DOI: https://doi.org/10.5217/ir.2021.00168

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
The fecal microbiota of Korean patients with inflammatory bowel disease (IBD) was investigated with respect to disease phenotypes and taxonomic biomarkers for diagnosis and prognosis of IBD.
Methods
Fecal samples from 70 ulcerative colitis (UC) patients, 39 Crohn’s disease (CD) patients, and 100 healthy control individuals (HC) were collected. The fecal samples were amplified via polymerase chain reaction and sequenced using Illumina MiSeq. The relationships between fecal bacteria and clinical phenotypes were analyzed using the EzBioCloud database and 16S microbiome pipeline.
Results
The alpha-diversity of fecal bacteria was significantly lower in UC and CD (P<0.05) compared to that in HC. Bacterial community compositions in UC and CD were significantly different from that of HC according to Bray-Curtis dissimilarities, and there was also a difference between community composition in UC and CD (P=0.01). In UC, alpha-diversity was further decreased when the disease was more severe and the extent of disease was greater, and community composition significantly differed depending on the extent of the disease. We identified 9 biomarkers of severity and 6 biomarkers of the extent of UC. We also identified 5 biomarkers of active disease and 3 biomarkers of ileocolonic involvement in CD. Lachnospiraceae and Ruminococcus gnavus were biomarkers for better prognosis in CD.
Conclusions
The fecal microbiota profiles of IBD patients were different from those of HC, and several bacterial taxa may be used as biomarkers to determine disease phenotypes and prognosis. These data may also help discover new therapeutic targets for IBD.

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Yu Kyung Jun, Da-Ae Yu, Yoo Min Han, Soo Ran Lee, Seong-Joon Koh, Hyunsun Park
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Risk of all-cause and cause-specific mortality associated with immune-mediated inflammatory diseases in Korea
Oh Chan Kwon, See Young Lee, Jaeyoung Chun, Kyungdo Han, Yuna Kim, Ryul Kim, Min-Chan Park, Jie-Hyun Kim, Young Hoon Youn, Hyojin Park
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Kwang Woo Kim
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Evaluation of Bacterial and Fungal Biomarkers for Differentiation and Prognosis of Patients with Inflammatory Bowel Disease
Hyuk Yoon, Sunghyouk Park, Yu Kyung Jun, Yonghoon Choi, Cheol Min Shin, Young Soo Park, Nayoung Kim, Dong Ho Lee
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A Machine Learning-Based Diagnostic Model for Crohn’s Disease and Ulcerative Colitis Utilizing Fecal Microbiome Analysis
Hyeonwoo Kim, Ji Eun Na, Sangsoo Kim, Tae-Oh Kim, Soo-Kyung Park, Chil-Woo Lee, Kyeong Ok Kim, Geom-Seog Seo, Min Suk Kim, Jae Myung Cha, Ja Seol Koo, Dong-Il Park
Microorganisms.2023; 12(1): 36. CrossRef

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Review

Microbiota

The role of microbiome in colorectal carcinogenesis and its clinical potential as a target for cancer treatment: Sang Hoon Kim, Yun Jeong Lim; Intest Res 2022;20(1):31-42. Published online May 21, 2021; DOI: https://doi.org/10.5217/ir.2021.00034

Abstract PDF PubReader ePub

The role of gut microbiome-intestinal immune complex in the development of colorectal cancer and its progression is well recognized. Accordingly, certain microbial strains tend to colonize or vanish in patients with colorectal cancer. Probiotics, prebiotics, and synbiotics are expected to exhibit both anti-tumor effects and chemopreventive effects during cancer treatment through mechanisms such as xenometabolism, immune interactions, and altered eco-community. Microbial modulation can also be safely used to prevent complications during peri-operational periods of colorectal surgery. A deeper understanding of the role of intestinal microbiota as a target for colorectal cancer treatment will lead the way to a better prognosis for colorectal cancer patients.

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Nazime Mercan Doğan, Naime Nur Bozbeyoğlu Kart
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Species-level identification of enterotype-specific microbial markers for colorectal cancer and adenoma
Ünzile Güven Gülhan, Emrah Nikerel, Tunahan Çakır, Fatih Erdoğan Sevilgen, Saliha Durmuş
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Paulina Adeniyi
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Yong Eun Park
The Korean Journal of Internal Medicine.2023; 38(2): 264. CrossRef
Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer
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Yeuni Yu, Donghyun Han, Hyomin Kim, Yun Hak Kim, Dongjun Lee
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Na Yuan, Xiaoyan Li, Meng Wang, Zhilin Zhang, Lu Qiao, Yamei Gao, Xinjian Xu, Jie Zhi, Yang Li, Zhongxin Li, Yitao Jia
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Nimalan Arjun Jeganathan, Emily R Davenport, Gregory S Yochum, Walter A Koltun
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The Interaction Between the Microbiome and Tumors
Yawen Zong, Yujie Zhou, Binyou Liao, Min Liao, Yangyang Shi, Yu Wei, Yuyao Huang, Xuedong Zhou, Lei Cheng, Biao Ren
Frontiers in Cellular and Infection Microbiology.2021;[Epub] CrossRef
Anti-inflammatory properties of Escherichia coli Nissle 1917 in a murine colitis model
Jihye Park, Da Hye Kim, Soochan Kim, Hyun Woo Ma, I Seul Park, Mijeong Son, Ji Hyung Kim, Yoojin Shin, Seung Won Kim, Jae Hee Cheon
Intestinal Research.2021; 19(4): 478. CrossRef
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Frontiers in Cellular and Infection Microbiology.2021;[Epub] CrossRef

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Original Article

Microbiota

Relationship between the gut microbiota and bile acid composition in the ileal mucosa of Crohn’s disease: Shigeki Bamba, Osamu Inatomi, Atsushi Nishida, Masashi Ohno, Takayuki Imai, Kenichiro Takahashi, Yuji Naito, Junichi Iwamoto, Akira Honda, Naohiro Inohara, Akira Andoh; Intest Res 2022;20(3):370-380. Published online May 14, 2021; DOI: https://doi.org/10.5217/ir.2021.00054

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Crosstalk between the gut microbiota and bile acid plays an important role in the pathogenesis of gastrointestinal disorders. We investigated the relationship between microbial structure and bile acid metabolism in the ileal mucosa of Crohn’s disease (CD).
Methods
Twelve non-CD controls and 38 CD patients in clinical remission were enrolled. Samples were collected from the distal ileum under balloon-assisted enteroscopy. Bile acid composition was analyzed by liquid chromatography-mass spectrometry. The gut microbiota was analyzed by 16S rRNA gene sequencing.
Results
The Shannon evenness index was significantly lower in endoscopically active lesions than in non-CD controls. β-Diversity, evaluated by the UniFrac metric, revealed a significant difference between the active lesions and non-CD controls (P=0.039). The relative abundance of Escherichia was significantly higher and that of Faecalibacterium and Roseburia was significantly lower in CD samples than in non-CD controls. The increased abundance of Escherichia was more prominent in active lesions than in inactive lesions. The proportion of conjugated bile acids was significantly higher in CD patients than in non-CD controls, but there was no difference in the proportion of primary or secondary bile acids. The genera Escherichia and Lactobacillus were positively correlated with the proportion of conjugated bile acids. On the other hand, Roseburia, Intestinibacter, and Faecalibacterium were negatively correlated with the proportion of conjugated bile acids.
Conclusions
Mucosa-associated dysbiosis and the alteration of bile acid composition were identified in the ileum of CD patients. These may play a role in the pathophysiology of ileal lesions in CD patients.

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Rupa Tharu, Geetika Malik Ahlawat, Savitesh Kushwaha, Poonam Khanna
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Gut microbes improve prognosis of Klebsiella pneumoniae pulmonary infection through the lung-gut axis
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Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease
Seung Yong Shin, Young Kim, Won-Seok Kim, Jung Min Moon, Kang-Moon Lee, Sung-Ae Jung, Hyesook Park, Eun Young Huh, Byung Chang Kim, Soo Chan Lee, Chang Hwan Choi
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Crohn’s disease: Why the ileum?
Nicolas Richard, Guillaume Savoye, Mathilde Leboutte, Asma Amamou, Subrata Ghosh, Rachel Marion-Letellier
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Tadakuni Monma, Junichi Iwamoto, Hajime Ueda, Makoto Tamamushi, Fumio Kakizaki, Naoki Konishi, Shoichiro Yara, Teruo Miyazaki, Takeshi Hirayama, Tadashi Ikegami, Akira Honda
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Review

Microbiota

Gut microbiome and checkpoint inhibitor colitis: Kanika Sehgal, Sahil Khanna; Intest Res 2021;19(4):360-364. Published online December 1, 2020; DOI: https://doi.org/10.5217/ir.2020.00116

Abstract PDF PubReader ePub

Immune checkpoint inhibitor therapies such as ipilimumab, are increasingly being used as a treatment option for a variety of cancers, including metastatic melanoma and have demonstrated effectively a prolonged survival. These agents have an immunological mode of action that predisposes patients to a number of immune-related adverse events, colitis being one of the most commonly encountered complications. The pathogenesis for the development of colitis is unclear, and there is a growing consensus that the ecosystem of the gastrointestinal microbiota plays a significant role. Based on this suspected connection, studies are being carried out to explore the changes in the microbiota in patients on these medications who develop colitis. Conceivably, the modulation of the gut microbiota could offer a therapeutic benefit. Fecal microbiota transplantation is one therapeutic option that is currently being investigated, though there are still more data needed to evaluate its efficacy. In this review, we recapitulate the mechanisms of action of immune checkpoint inhibitors, their adverse events, with a focus on colitis and the role gut microbiota are suspected to play, and finally discuss the microbiota modulation therapies being investigated.

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Focused Review

Microbiota

Importance of nutritional therapy in the management of intestinal diseases: beyond energy and nutrient supply: Seong-Eun Kim; Intest Res 2019;17(4):443-454. Published online September 4, 2019; DOI: https://doi.org/10.5217/ir.2019.00075

Abstract PDF PubReader ePub

The gut is an immune-microbiome-epithelial complex. Gut microbiome-host interactions have widespread biological implications, and the role of this complex system extends beyond the digestion of food and nutrient absorption. Dietary nutrients can affect this complex and play a key role in determining gut homeostasis to maintain host health. In this article, we review various dietary nutrients and their contribution to the pathogenesis and treatment of various intestinal diseases including inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, and diverticulitis, among other such disorders. A better understanding of diet-host-gut microbiome interactions is essential to provide beneficial nutrients for gut health and to limit nutritional hazards to ensure successful nutritional management of gastrointestinal conditions in clinical practice.

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Original Articles

Microbiota

Evaluation of commercial probiotic lactic cultures against biofilm formation by Cronobacter sakazakii: Anubhav Jamwal, Kavita Sharma, Rajni Chauhan, Saurabh Bansal, Gunjan Goel; Intest Res 2019;17(2):192-201. Published online December 3, 2018; DOI: https://doi.org/10.5217/ir.2018.00106

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Cronobacter sakazakii, an emergent pathogen is considered as a major concern to infants and neonates fed on reconstituted powdered infant milk formula. In conjunction with many other factors, biofilm forming capacity adds to its pathogenic potential. In view of the facts that infants are at highest risk to C. sakazakii infections, and emerging antibiotic resistance among pathogens, it is imperative to evaluate probiotic cultures for their efficacy against C. sakazakii. Therefore, pure probiotic strains were isolated from commercial probiotic products and tested for their antimicrobial and anti-biofilm activities against C. sakazakii.
Methods
A total of 6 probiotic strains were tested for their antibiotic susceptibility followed by antimicrobial activity using cell-free supernatant (CFS) against C. sakazakii. The inhibitory activity of CFS against biofilm formation by C. sakazakii was determined using standard crystal violet assay and microscopic observations.
Results
All the probiotic strains were sensitive to ampicillin, tetracycline, vancomycin and carbenicillin whereas most of the strains were resistant to erythromycin and novobiocin. Four of the 6 probiotic derived CFS possessed antimicrobial activity against C. sakazakii at a level of 40 μL. A higher biofilm inhibitory activity (>80%) was observed at initial stages of biofilm formation with weaker activity during longer incubation upto 48 hours (50%–60%).
Conclusions
The study indicated the efficacy of isolated commercial probiotics strains as potential inhibitor of biofilm formation by C. sakazakii and could be further explored for novel bioactive molecules to limit the emerging infections of C. sakazakii.

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Microbiota

Development and diversity of lactic acid producing bacteria and bifidobacteria in healthy full term Indian infants from Himachal Pradesh: Sampan Attri, Rishi Mahajan, Gunjan Goel; Intest Res 2018;16(4):529-536. Published online October 10, 2018; DOI: https://doi.org/10.5217/ir.2018.00050

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
The initial microbial colonization is a crucial step for the healthy development of an infant. Previous studies from India reported the dominance of target microbial species among Indian infants without any analysis on the diversity of target groups. This is the first study from India with an objective to investigate the establishment and diversity of lactic acid producing bacteria (LAB) and bifidobacteria in vaginally delivered, full term, breastfed infants for the first 4 months after birth.
Methods
Present study used polymerase chain reaction-denaturating gradient gel electrophoresis (PCR-DGGE) based sequence analysis of LAB and bifidobacteria in healthy infants. The results were used to compare the development and early colonization by LAB and bifidobacteria using diversity indices during the initial months of development of gut microbiota in infants.
Results
During the first 4 months, the Shannon diversity index (H) of LAB increased from 1.16 to 1.318 and for bifidobacteria the H increased from 0.975 to 1.293 (P<0.05). Higher Sorenson’s pair wise similarity coefficient was observed for LAB and bifidobacteria during 2nd and the 3rd month. The species of the genera Enterococcus, Streptococcus, and Lactobacillus were dominant among the LAB group whereas Bifidobacterium breve was dominant species among Bifidobacterium group.
Conclusions
Our results indicate that in breast fed infants, the microbial diversity of LAB and bifidobacteria increased during the period of study.

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Development and Functions of the Infant Gut Microflora: Westernvs. Indian Infants
Lalit Bharadia, Neha Agrawal, Nandan Joshi
International Journal of Pediatrics.2020; 2020: 1. CrossRef

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Microbiota

Characterization of the fecal microbiota differs between age groups in Koreans: Sun-Young Kook, Yunjeong Kim, Ben Kang, Yon Ho Choe, Young-Ho Kim, Seokjin Kim; Intest Res 2018;16(2):246-254. Published online April 30, 2018; DOI: https://doi.org/10.5217/ir.2018.16.2.246

Abstract PDF Supplementary Material PubReader ePub

<b>Background/Aims</b><br/>

Tens of trillions of microorganisms constitute the gut microbiota of the human body. The microbiota plays a critical role in maintaining host immunity and metabolism. Analyses of the gut microbial composition in Korea are limited to a few studies consisting of small sample sizes. To investigate the gut microbial community in a large sample of healthy Koreans, we analyzed the 16S ribosomal RNA of 4 representative bacterial genera Lactobacillus, Bifidobacterium, Bacteroides, and Clostridium.

Methods

A total of 378 DNA samples extracted from 164 infants and 214 adults were analyzed using quantitative real-time polymerase chain reaction.

Results

Analysis of 16S ribosomal RNA of 4 representative bacterial genera Lactobacillus, Bifidobacterium, Bacteroides, and Clostridium showed that the gut microbiota in infants had higher relative abundances of Bifidobacterium and Lactobacillus than that in adults, which was dominated by Bacteroides and Clostridium.

Conclusions

To the best of our knowledge, this was the first study evaluating the distinct characteristics of the microbial community of Korean infants and adults. The differences between the 2 populations suggest that external factors such as age, diet, and the environment are important contributing factors to the change in gut microbial composition during development.

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