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If you develop symptoms while at the conference, please discontinue your attendance and immediately seek medical care. AOM has the right and duty to restrict access to anyone not following conference, city, or state guidelines. This study aimed to analyze the differential effects of Nrf2 KO on the gut microbiota composition depending on sex and CRC induction and to identify the role of Nrf2-mediated bacterial composition alterations in the development of CRC.
The design of this study is illustrated in Figure 1A. Therefore, some of the data used in this study overlaps with the previous results. The gut microbial composition at the species level among different groups was assessed based on the generalized UniFrac distances. Thus, Nrf2 differentially affected the gut bacterial composition depending on sex and CRC induction. We further analyzed the alpha diversity of the intestinal microbiota based on sex, CRC induction, and Nrf2 genotype.
Interestingly, the gut microbial diversity indices, including OTU count, Chao1 index, and Shannon index, in the male Nrf2 KO control group were significantly lower than those in the male WT control group Figure 3 and Table 1. These results indicate that Nrf2 KO differentially altered the intestinal microbial diversity depending on sex and CRC induction. Analysis of species richness and diversity of the gut microbiome.
Whiskers show the minimum and maximum values. Data are presented as the medians. Mann—Whitney U-test for comparison difference between independent two groups was performed. At the phylum level, the abundance of only Bacteroidetes and Verrucomicrobia varied between male and female mice. At the family level, sex-specific changes in the abundance of Rikenellaceae , Prevotellaceae , Odoribacteraceae , Muribaculaceae phylum: Bacteroidetes , Ruminococcaceae , Lactobacillaceae phylum: Firmicutes , and Akkermansiaceae phylum: Verrucomicrobia were observed in all groups Supplementary Figures S5A, B.
Gut microbiota composition at the phylum level. The abundance indicates the percentage of each phylum in total microorganisms. Mann—Whitney U-test was used to analyze the difference between two independent groups in A—D.
The p -values calculated from the Kruskal—Wallis test is shown in the figure. Nrf2 KO altered the intestinal microbial composition at the phylum level, especially the abundance of Firmicutes , Bacteroidetes , and Proteobacteria. Interestingly, the abundance of Proteobacteria in all Nrf2 KO 1.
The abundance of 11 gut bacteria, which were functionally known as commensal bacteria or opportunistic pathogens, significantly changed in this study Figures 5 — 7.
Sex-specific alterations in the abundance of the gut microbiota composition examined using LEfSe. Bar plots at the species level with significant differences in abundance based on LEfSe. Each color on the species name indicates the characteristics of each genus: yellow for commensal bacteria, orange for opportunistic pathogens, and green for not characterized bacteria.
The p -values were determined using the non-parametric factorial Kruskal—Wallis sum-rank test. E The ratio of commensal bacteria to opportunistic pathogens based on the LEfSe results in each comparison group. Bar plots of the LEfSe results, which were generated based on the criteria mentioned in the legend of Figure 5.
Bar plots at the species level with significant differences in abundance based on the LEfSe results. Additionally, LEfSe revealed alterations in the abundance of six sex-specific bacteria two commensal bacteria, Lactobacillus gasseri and Lactobacillus murinus ; three opportunistic pathogens, Helicobacter pylori , Mucispirillum schaedleri , and Clostridium indolis ; one dual-role bacterium, Akkermansia muciniphila Figure 5 , nine CRC-specific bacteria four commensal bacteria, Muribaculum intestinale , Bacteroides uniformis , Parabacteroides goldsteinii , L.
The p -values were calculated using the non-parametric factorial Kruskal—Wallis sum-rank test. However, the sex-specific changes in the abundance of A. The abundance of L.
However, the sex-specific changes in the abundance of L. At week 16 post-AOM administration, the abundance of A. Interestingly, the abundance of A. The abundance of B. However, the abundance of B. The abundance of the two selected commensal bacterial species, which are L. The abundance of M. Additionally, the abundance of M. However, the abundance of M. Additionally, there was no difference in the abundance of M. The ratio of commensal bacteria to opportunistic pathogens in the female Nrf2 KO control group was lower than that in the female WT control group.
However, sex-specific changes in the abundance of L. Sex-specific changes in the abundance of L. Next, the effects of L. Negative correlation between Lactobacillus murinus and tumor numbers in the colon. The abundance of Lactobacillus murinus was significantly correlated with total tumor numbers H. Dotted line indicates the regression line. Tumor grade: 0, no tumor; 1, low-grade adenoma; 2, high-grade adenoma; 3, mucosal invasive adenocarcinoma; 4, submucosal invasive adenocarcinoma.
Interestingly, the abundance of B. Next, the correlation between the abundance of B. Positive correlation between Bacteroides vulgatus and colitis-associated CRC indices. E-J The abundance of Bacteroides vulgatus was significantly correlated with tumor indices. To classify the properties of intestinal microflora that cannot be determined using LEfSe, all samples were further assessed based on the enterotypes. All groups were divided into two enterotypes because the highest CH value was 2.
Meanwhile, A. These results indicate that A. The findings of this study indicated that Nrf2 KO was associated with sex-specific and CRC-specific alterations in the gut microbiome composition in the mouse model. Nrf2 KO differentially altered the abundance of two bacterial species, which are L. Interestingly, the sex-specific difference in the abundance of L.
In contrast, the CRC-specific difference in the abundance of B. Illustrative summary. The balance of the gut microbiome is critical for the maintenance of host homeostasis. Dysbiosis can lead to the development of diseases, such as cancer, metabolic diseases, allergies, and immunological disorders Shanahan, Previously, we investigated the role of Nrf2 in colitis-associated CRC progression. The previously reported results of the stool samples were used in this study to determine the correlation between the host gut microbiome composition and other factors, such as sex, CRC, and Nrf2 KO.
Various indicators of gut microbial diversity have been developed to estimate and examine the characteristics of microbial communities. Generally, alpha diversity, an indicator of species richness and diversity, is a characteristic of the gut microbiota of healthy individuals Le Chatelier et al. In contrast, low diversity of the gut microbiome is associated with various inflammatory and metabolic diseases, such as obesity Turnbaugh et al.
Furthermore, an independent analysis of the gut microbiota using 89 different inbred mouse strains revealed that the gut microbiota composition and diversity varied between male and female mice within each strain Org et al. However, most preclinical studies have used male animals, whereas some studies have not specified the sex of the animal Jahng and Kim, In this study, both male and female mice were used to investigate the effect of sex, CRC, and Nrf2 on the gut microbiota composition and diversity.
These results were not consistent with those of previous studies that reported sex-specific differences in gut microbial diversity. Similarly, there was a distinct sex differences on microbiota in the control group which also disappeared in the IL KO-induced inflammatory bowel disease model.
Furthermore, sex-specific alterations in the gut microbial diversity were not observed in our previous studies using F rats and ICR mice Lee et al. Thus, there are inconsistent findings on the sex-specific alterations in gut microbial composition. Each weighted index measures different aspects of diversity. Hence, the diversity index does not reveal the actual diversity.
Furthermore, these disparities might be due to differences in animal models, housing conditions, and diet used in different studies. The phyla Firmicutes and Bacteroidetes are reported to be the predominant bacterial populations in the human gastrointestinal microbiome Collado et al. These results are consistent with those of our previous study involving ICR-background mice Song et al. In this study, we identified sex-specific A.
Of these, Nrf2 KO affected the abundance of only L. A large cohort study demonstrated that women in the Netherlands exhibited an increased abundance of A. In the Japanese population, the abundance of members belonging to the genus Akkermansia in women was significantly higher than that in men Gao et al.
Furthermore, A. However, there are conflicting reports on the role of A. Furthermore, patients with multiple sclerosis exhibited a higher abundance of A. Therefore, this study did not classify A. Most recent studies focus on the correlation between A. Generally, L. Lactobacillus species are predominantly enriched in the vaginal tracts of European women Fettweis et al. Fraga et al.
Recently, Singer et al. The administration of L. In this study, the abundance of L. Furthermore, correlation analysis between the gut microbiome and disease index revealed that the abundance of L. Previously, we reported the lack of sex-specific differences in the abundance of L. Moreover, L. However, there are no studies on the correlation between L. Bacteroides species are reported to induce colitis based on the host genotype in a mouse model of inflammatory bowel disease Bloom et al.
Bloom et al. Furthermore, metagenome sequencing revealed that B. Consistent with previous reports, this study demonstrated that the abundance of B.
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