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Original Articles
Impact of stool transplantation and metformin on polyp reduction and inflammation in an APC Min mouse model
Yeon Ji Kim, Jiwon Lee, Eunmi Lee, Seun Ja Park, Jae Hyun Kim
Received January 30, 2025  Accepted March 18, 2025  Published online May 19, 2025  
DOI: https://doi.org/10.5217/ir.2025.00011    [Epub ahead of print]
AbstractAbstract PDFPubReaderePub
Background/Aims
Familial adenomatous polyposis is a hereditary condition characterized by numerous adenomatous polyps in the colon and rectum, significantly increasing colorectal cancer risk. Current management strategies, such as prophylactic colectomy, are invasive and have long-term consequences, highlighting the need for alternative therapies. This study aimed to evaluate whether stool transplantation and metformin therapy synergistically reduce polyp formation and inflammation.
Methods
APC Min mice were divided into 4 groups: control, anti-control (antibiotic pretreatment), stool (stool transplantation), and stool+metformin. Polyp burden, bacterial abundance, inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-10), and tumorigenic markers (NF-κB, Cox2, c-myc, β-catenin) were assessed using messenger RNA (mRNA) and protein analyses of intestinal tissues, along with serum and fecal microbiota evaluations.
Results
Stool transplantation combined with metformin significantly reduced bacterial abundance and polyp burden. The anti-control group showed similar reductions, suggesting suppression of gut microbiota re-establishment. TNF-α and IL-10 levels remained unchanged, but a significant increase in IL-6 was observed in the stool+metformin group’s intestinal tissues, indicating localized immune activation. Intestinal Cox2 mRNA expression was reduced in the combination group, correlating with polyp suppression. Protein levels of NF-κB, Cox2, and β-catenin showed no significant changes in vivo, while in vitro experiments revealed a decrease in NF-κB and an increase in Cox2, suggesting complex regulation of inflammation-related pathways.
Conclusions
Stool transplantation combined with metformin reduces polyp burden in APC Min mice through gut microbiota modulation and localized immune activation. These findings support the therapeutic potential of this combination treatment for familial adenomatous polyposis.
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Miscellaneous
Melatonin in the colon modulates intestinal microbiota in response to stress and sleep deprivation
Young Sook Park, Soo Hyung Kim, Jong Won Park, Younglim Kho, Pu Rum Seok, Jae-Ho Shin, Yoon Ji Choi, Jin-Hyun Jun, Hee Chan Jung, Eun Kyung Kim
Intest Res 2020;18(3):325-336.   Published online June 23, 2020
DOI: https://doi.org/10.5217/ir.2019.00093
AbstractAbstract PDFPubReaderePub
Background/Aims
Stress is closely related to the deterioration of digestive disease. Melatonin has potent anti-inflammatory properties. The objective of this study was to determine the effect of water stress (WS) and sleep deprivation (SD) on intestinal microbiota and roles of melatonin in stressful condition.
Methods
We used C57BL/6 mice and specially designed water bath for stress and SD for 10 days. We measured melatonin concentrations in serum, feces, and colon tissues by high-performance liquid chromatography. Genomic DNA was extracted from feces and amplified using primers targeting V3 to V4 regions of bacterial 16S ribosomal RNA genes.
Results
Compared to the control, melatonin concentration was lower in the WS and SD. Fecal concentration was 0.132 pg/mL in control, 0.062 pg/mL in WS, and 0.068 pg/mL in SD. In colon tissue, it was 0.45 pg/mL in control, 0.007 pg/mL in WS, and 0.03 pg/mL in SD. After melatonin treatment, melatonin concentrations in feces and colon tissue were recovered to the level of control. Metagenomic analysis of microbiota showed abundance in colitogenic microbiota in WS and SD. Melatonin injection attenuated this harmful effect. WS and SD showed decreased Lactobacillales and increased Erysipelotrichales and Enterobacteriales. Melatonin treatment increased Akkermansia muciniphila and Lactobacillus and decreased Bacteroides massiliensis and Erysipelotrichaceae.
Conclusions
This study showed that stress and SD could affect intestinal dysbiosis and increase colitogenic microbiota, which could contribute to the aggravating digestive disease. Melatonin concentrations in feces and colon tissue decreased under WS and SD. Melatonin treatment brought recovery of melatonin concentration in colon tissue and modulating dysbiosis of intestinal microbiota.

Citations

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Functional bowel disorders
Is stool frequency associated with the richness and community composition of gut microbiota?
Hye Jung Kwon, Jong Hyun Lim, Dongmin Kang, Sanghyun Lim, Seun Ja Park, Jae Hyun Kim
Intest Res 2019;17(3):419-426.   Published online February 7, 2019
DOI: https://doi.org/10.5217/ir.2018.00149
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Background/Aims
Recently, a number of studies have reported that the gut microbiota could contribute to human conditions, including obesity, inflammation, cancer development, and behavior. We hypothesized that the composition and distribution of gut microbiota are different according to stool frequency, and attempted to identify the association between gut microbiota and stool frequency.
Methods
We collected fecal samples from healthy individuals divided into 3 groups according to stool frequency: group 1, a small number of defecation (≤2 times/wk); group 2, normal defecation (1 time/day or 1 time/2 day); and group 3, a large number of defecation (≥2–3 times/day). We evaluated the composition and distribution of the gut microbiota in each group via 16S rRNA-based taxonomic profiling of the fecal samples.
Results
Fecal samples were collected from a total of 60 individuals (31 men and 29 women, aged 34.1±5.88 years), and each group comprised 20 individuals. The microbial richness of group 1 was significantly higher than that of group 3 and tended to decrease with increasing number of defecation (P<0.05). The biological community composition was fairly different according to the number of defecation, and Bacteroidetes to Firmicutes ratio was higher in group 1 than in the other groups. Moreover, we found specific strains at the family and genus levels in groups 1 and 3.
Conclusions
Bacteroidetes to Firmicutes ratio and the abundance of Bifidobacterium were different according to the stool frequency, and specific bacteria were identified in the subjects with large and small numbers of defecation, respectively. These findings suggest that stool frequency might be associated with the richness and community composition of the gut microbiota.

Citations

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Review
Pathogenic role of the gut microbiota in gastrointestinal diseases
Hiroko Nagao-Kitamoto, Sho Kitamoto, Peter Kuffa, Nobuhiko Kamada
Intest Res 2016;14(2):127-138.   Published online April 27, 2016
DOI: https://doi.org/10.5217/ir.2016.14.2.127
AbstractAbstract PDFPubReaderePub

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.

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