Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice

The gut microbiota plays an important role in the development of colorectal tumors. However, the underlying mechanisms remain unclear. In this study, we examined the effects of fecal microbiota transplantation (FMT) on azoxymethane (AOM)-induced colorectal tumors in obese mice. We divided the study...

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Main Authors: Hiroshi Matsumoto, Tingting Gu, Shogen Yo, Momoyo Sasahira, Shuzo Monden, Takehiro Ninomiya, Motoyasu Osawa, Osamu Handa, Eiji Umegaki, Akiko Shiotani
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Language:English
Published: MDPI AG 2025-04-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/5/1009
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author Hiroshi Matsumoto
Tingting Gu
Shogen Yo
Momoyo Sasahira
Shuzo Monden
Takehiro Ninomiya
Motoyasu Osawa
Osamu Handa
Eiji Umegaki
Akiko Shiotani
author_facet Hiroshi Matsumoto
Tingting Gu
Shogen Yo
Momoyo Sasahira
Shuzo Monden
Takehiro Ninomiya
Motoyasu Osawa
Osamu Handa
Eiji Umegaki
Akiko Shiotani
author_sort Hiroshi Matsumoto
collection DOAJ
description The gut microbiota plays an important role in the development of colorectal tumors. However, the underlying mechanisms remain unclear. In this study, we examined the effects of fecal microbiota transplantation (FMT) on azoxymethane (AOM)-induced colorectal tumors in obese mice. We divided the study subjects into the following five groups: high-fat diet (HFD), normal diet (ND), ND+exercise (Ex), HFD+FMT from ND-alone donor (HFD+FMT(ND alone)), and HFD+FMT from ND+Ex donor (HFD+FMT(ND+Ex)). The Ex group performed treadmill exercise for 15 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiome analysis. The deoxyribonucleic acid sample was collected from the feces and colonic mucosa, and V3–V4 amplicon sequencing analysis of the 16S rRNA gene was performed using MiSeq. The number of polyps was significantly lower in the ND (6.0 ± 1.6) and ND+Ex (1.8 ± 1.3) groups than in the HFD group (11.4 ± 1.5). The ND+Ex group had significantly fewer polyps than the ND group. The HFD+FMT(ND alone) (5.2 ± 0.8) and HFD+FMT(ND+Ex) (2.8 ± 2.6) groups also had significantly fewer polyps than the HFD group. The IL-15 mRNA levels in the colonic tissues were significantly higher in the HFD+FMT(ND alone) group than in the ND group. Fecal ω-muricholic acid concentrations were significantly higher in the HFD+FMT(ND alone) group than in the ND group and in the HFD+FMT(ND+Ex) group than in the ND+Ex group. The ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of <i>Lacyobacillaceae</i> than the HFD group. In the FMT group, <i>Erysipelotrichaceae</i> and <i>Tannerellaceae</i> were significantly less abundant. Compared with the HFD group, the ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of <i>Muribaculaceae</i> and a significantly higher abundance of <i>Lactobacillaceae</i> and <i>Rikenellaceae</i> in common among the ND and ND+Ex groups. The common and significantly less common species were <i>Bacteroidaceae</i> in the FMT group and <i>Lactobacillaceae</i> and <i>Rikenellaceae</i> in the ND alone and ND+Ex groups. <i>Bacteroidaceae</i> and <i>Lachnospiraceae</i> were significantly less common in the FMT group. We found that FMT inhibited AOM-induced colorectal tumorigenesis in obese mice. Furthermore, the fecal concentrations of short-chain fatty acids, bile acids, microbiota, and mucosa-associated microbiota differed between the FMT and diet/EX groups, suggesting that the inhibitory effect of FMT on colorectal tumorigenesis may be due to mechanisms different from those of ND alone and ND+Ex.
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spelling doaj-art-e6b06f37556c4367ba1bdd61749041d02025-08-20T01:56:35ZengMDPI AGMicroorganisms2076-26072025-04-01135100910.3390/microorganisms13051009Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese MiceHiroshi Matsumoto0Tingting Gu1Shogen Yo2Momoyo Sasahira3Shuzo Monden4Takehiro Ninomiya5Motoyasu Osawa6Osamu Handa7Eiji Umegaki8Akiko Shiotani9Department of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Gastroenterology, Kawasaki Medical School, Kurashiki 701-0192, JapanThe gut microbiota plays an important role in the development of colorectal tumors. However, the underlying mechanisms remain unclear. In this study, we examined the effects of fecal microbiota transplantation (FMT) on azoxymethane (AOM)-induced colorectal tumors in obese mice. We divided the study subjects into the following five groups: high-fat diet (HFD), normal diet (ND), ND+exercise (Ex), HFD+FMT from ND-alone donor (HFD+FMT(ND alone)), and HFD+FMT from ND+Ex donor (HFD+FMT(ND+Ex)). The Ex group performed treadmill exercise for 15 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiome analysis. The deoxyribonucleic acid sample was collected from the feces and colonic mucosa, and V3–V4 amplicon sequencing analysis of the 16S rRNA gene was performed using MiSeq. The number of polyps was significantly lower in the ND (6.0 ± 1.6) and ND+Ex (1.8 ± 1.3) groups than in the HFD group (11.4 ± 1.5). The ND+Ex group had significantly fewer polyps than the ND group. The HFD+FMT(ND alone) (5.2 ± 0.8) and HFD+FMT(ND+Ex) (2.8 ± 2.6) groups also had significantly fewer polyps than the HFD group. The IL-15 mRNA levels in the colonic tissues were significantly higher in the HFD+FMT(ND alone) group than in the ND group. Fecal ω-muricholic acid concentrations were significantly higher in the HFD+FMT(ND alone) group than in the ND group and in the HFD+FMT(ND+Ex) group than in the ND+Ex group. The ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of <i>Lacyobacillaceae</i> than the HFD group. In the FMT group, <i>Erysipelotrichaceae</i> and <i>Tannerellaceae</i> were significantly less abundant. Compared with the HFD group, the ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of <i>Muribaculaceae</i> and a significantly higher abundance of <i>Lactobacillaceae</i> and <i>Rikenellaceae</i> in common among the ND and ND+Ex groups. The common and significantly less common species were <i>Bacteroidaceae</i> in the FMT group and <i>Lactobacillaceae</i> and <i>Rikenellaceae</i> in the ND alone and ND+Ex groups. <i>Bacteroidaceae</i> and <i>Lachnospiraceae</i> were significantly less common in the FMT group. We found that FMT inhibited AOM-induced colorectal tumorigenesis in obese mice. Furthermore, the fecal concentrations of short-chain fatty acids, bile acids, microbiota, and mucosa-associated microbiota differed between the FMT and diet/EX groups, suggesting that the inhibitory effect of FMT on colorectal tumorigenesis may be due to mechanisms different from those of ND alone and ND+Ex.https://www.mdpi.com/2076-2607/13/5/1009fecal microbiota transplantation (FMT)colorectal cancerobesityexercisehigh-fat diet
spellingShingle Hiroshi Matsumoto
Tingting Gu
Shogen Yo
Momoyo Sasahira
Shuzo Monden
Takehiro Ninomiya
Motoyasu Osawa
Osamu Handa
Eiji Umegaki
Akiko Shiotani
Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice
Microorganisms
fecal microbiota transplantation (FMT)
colorectal cancer
obesity
exercise
high-fat diet
title Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice
title_full Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice
title_fullStr Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice
title_full_unstemmed Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice
title_short Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice
title_sort fecal microbiota transplantation using donor stool obtained from exercised mice suppresses colonic tumor development induced by azoxymethane in high fat diet induced obese mice
topic fecal microbiota transplantation (FMT)
colorectal cancer
obesity
exercise
high-fat diet
url https://www.mdpi.com/2076-2607/13/5/1009
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