Source: UNIV OF MASSACHUSETTS submitted to NRP
INCORPORATING MUSHROOM INTO WESTERN-STYLE DIET TO IMPROVE GUT HEALTH: COMBINATIONAL IMPACT ON TURICIBACTER-SEROTONIN INTERACTION
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
ACTIVE
Funding Source
Reporting Frequency
Annual
Accession No.
1028298
Grant No.
2022-67018-36986
Cumulative Award Amt.
$299,999.00
Proposal No.
2021-09025
Multistate No.
(N/A)
Project Start Date
Mar 1, 2022
Project End Date
Feb 28, 2026
Grant Year
2022
Program Code
[A1343]- Food and Human Health
Recipient Organization
UNIV OF MASSACHUSETTS
(N/A)
AMHERST,MA 01003
Performing Department
Dept: Nutrition
Non Technical Summary
The Western-Style Diet (WSD) represents one of the major contributors to the current rapid increase of obesity and Western-style diseases. However, effective dietary strategies precisely based on cellular and molecular mechanisms to improve the quality of WSD are still limited. Intestinal dysfunction is considered contributing significantly to the development of WSD-related diseases. In a series of our previous studies, we observed that a rarely studied bacterium, Turicibacter, is almost completely depleted by dietary obesity but not genetic obesity. Mushrooms possess a unique dietary composition rich with multiple nutrients that are lacking in WSD, making it a perfect supplement as a natural whole food to improve the quality of WSD and gut health. The objectives of this seed grant is to a) determine the role of Turicibacter in WSD-related intestinal dysfunction, b) examine the effect of oyster mushroom on reshaping gut microbiome towards improving WSD-impaired gut health. The completion of this strengthening seed project will not only provide the mechanistic understanding of the role of Turicibacter in dietary obesity and gut health, but also provide important insight into mushrooms as a whole-food approach to improve the quality of WSD and gut health. As Turicibacter is a rarely studied bacterium, this seed project will provide necessary preliminary data for future funding for comprehensive mechanistic studies (Turicibacter-serotonin interaction) and clinical trials (oyster mushroom) to improve our food systems and reduce risks of WSD-associated diseases.
Animal Health Component
50%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7021470101040%
7021470110030%
7021470109030%
Goals / Objectives
The long-term goal is to develop whole-food approaches to improve WSD-impaired gut health and thereby to reduce risks of related Western-style diseases. The objectives of this seed grant are:a) To determine the role of Turicibacter in ameliorating the intestinal dysfunction associated with WSD-induced obesity.b) To examine the effect of incorporating oyster mushroom into WSD on reshaping the gut microbiome towards improving gut health, especially the combinational impact on Turicibacter-serotonin interaction.The completion of this strengthening seed project will not only provide the mechanistic understanding of the role of Turicibacter in dietary obesity and gut health, but also provide important insight into mushrooms as a whole-food approach to improve the quality of WSD and gut health.
Project Methods
This project proposed pre-clinical animal studies to understand the molecular mechanisms by which Turicibacter influences obesity and gut health and how mushroom (oyster) can be used to improve the quality of WSD diet. Two genetically-engineered animal models, Db/Db obese model and IL-10 knockout model, will be used in this project. Gut microbiome and inflammatory cytokine profile will be analyzed. Results and new findings will be delivered to the public via conference presentations and publications.

Progress 03/01/24 to 02/28/25

Outputs
Target Audience:During the reporting period from March 1, 2024, to February 28, 2025, this project provided research training for a diverse group of students. The cohort included two PhD students, one master's student, and two undergraduate students conducting their dissertations, theses, or independent projects primarily in my laboratory. Additionally, six other PhD students gained biomedical laboratory skills and conducted parts of their projects in the lab. Students primarily based in my lab collaborated closely to learn and perform key biochemical and molecular assays, focusing on analyzing samples from our animal study investigating the effects of a Western-style diet supplemented with mushrooms. Their efforts centered on characterizing gut health, with completed assays including gut microbiome sequencing, inflammatory cytokine profiling, assessments of gut barrier functions, and analyses of tumorigenic signaling pathways. This hands-on involvement provided the students with valuable training and experience in biomedical research. The target audience who may benefit from my project activities through our publications and presentations on professional conferences include students, research scientists, registered dietitians, nutritional professionals, and general communities who are interested in nutrition and health. This project has resulted in one publication (Lin TC et al 2023. Front Pharmacol. PMID: 37663253) in the last reporting cycle (2023-2024), and two articles (Tang Y et al 2024. Nutr Res. PMID: 38763113, and Lin TC et al 2024. Nutrients. PMID: 39125288) published in this reporting cycle (2024-2025). Changes/Problems:In our original proposal, we proposed to test the improvement of gut health by incorporating oyster mushroom into Western-style diet. Due to challenge to obtain UVB-treatment oyster mushroom powder. We switched to shiitake mushroom. Both oyster and shiitake are effective in vitamin D-production via UVB treatment, and have similar profile of other nutrients, such as fiber. In addition, both of them are produced in US and commonly consumed by US population. Therefore, the ultimate goal of this project was not changed. Additionally, we expanded our project to include two key initiatives: 1) investigating the potential of the ancient medicinal mushroom Antrodia camphorata to enhance the quality of a Western-style diet and suppress intestinal tumorigenesis, and 2) exploring how a Western-style diet during early life affects the gut-breast axis and alters the mammary microenvironment. These initiatives align closely with the project's overarching goal of incorporating mushrooms into a Western-style diet to promote human health. What opportunities for training and professional development has the project provided?As outlined in the "Target Audiences" section, this USDA grant supported research training during this reporting year for two PhD students, one master's student, and two undergraduate students, along with six additional PhD students from other laboratories. Through hands-on participation in various tasks, these students gained valuable experience and training in biomedical research. How have the results been disseminated to communities of interest?The results have been disseminated to communities of interest through publications in peer-reviewed journals and presentations at professional conferences. These efforts have reached nutrition research scientists, registered dietitians, nutritional professionals, and general communities, as well as undergraduate and graduate students with an interest in nutrition and health. These dissemination activities ensure that a diverse audience benefits from our research findings. What do you plan to do during the next reporting period to accomplish the goals?We have almost reached the end of the project. We have achieved successful completion of this project and resulted in a total of 4 publications. We demonstrated a potential of incorporating mushroom into western-style diet to improve gut health, with a particular focus on early-life nutrition. Our findings demonstrated that the integration of mushroom into a high-fat western-style diet in early life can alter the gut microbiota, suppress inflammatory responses, and create a microenvironment towards suppressing intestinal tumorigenesis later in life. Moreover, we extended to investigate how western-style diet in early-life influenced the gut-breast axis and altered the mammary microenvironment and produced some exciting data as detailed in two publications (Tang Y et al., 2023, Current Oncology, PMID: 37185433 and Tang Y et al., 2024, Nutrition Research, PMID: 38763113). As described above, we are building on this research by conducting another animal study to evaluate the benefits of incorporating a more commonly available mushroom, Shiitake, as a whole-food supplement in a Western-style diet to enhance gut health and reduce the risk of chronic diseases. The animal study was completed during the 2022-2023 reporting cycle, with plans to finalize all biochemical and molecular analyses in the 2023-2024 extension reporting cycle. However, a lab reallocation from Chenoweth Laboratory to the newly renovated Goessmann Laboratory caused a significant disruption, delaying laboratory work by approximately one semester. As a result, some biomarker measurements remain ongoing. To address this, we are requesting a second extension (from March 1, 2025, to February 28, 2026) to complete the remaining assays. Although we anticipate needing only six months to finalize the analyses, the full-year extension will provide an opportunity to summarize our findings comprehensively and propose studies to further develop dietary strategies to improve the quality of Western-style diet for gut health by leveraging the distinctive nutritional properties of mushrooms.

Impacts
What was accomplished under these goals? 1. We conducted an animal study to explore the potential benefits of incorporating mushrooms into a Western-style diet to improve gut health, with a particular focus on early-life nutrition. Our findings revealed that supplementing a high-fat diet with a specific medicinal mushroom, Antrodia camphorata,during early life significantly altered gut microbiota and inhibited early-onset intestinal tumorigenesis in APC(1638N) mice later in life. These results are detailed in our publication listed in the "Products" section. 2. This funding project also partially supported another initiative to investigate the mechanisms by which a high fat Western-style diet influences the gut-breast axis and thereby alters the mammary microenvironment. This research has yielded compelling data, culminating in the publication of a research article during the previous reporting cycle (Tang Y et al., 2023, Current Oncology, PMID: 37185433) and a second article during the current reporting cycle (Tang Y et al., 2024, Nutrition Research, PMID: 38763113), as shown in the "Products" section 3. We explored the potential of the medicinal mushroom Antrodia camphorata to reduce intestinal tumorigenesis. Expanding on this research, we conducted another animal study to examine the benefits of incorporating a more commonly available mushroom, Shiitake, as a whole-food supplement in a Western-style diet to enhance gut health and reduce the risk of chronic diseases. The study included four dietary groups: a low-fat control diet (LF, 10% kcal from fat), a high-fat Western-style diet (HF, 45% kcal from fat), and LF and HF diets supplemented with 5% Shiitake mushroom (LFM and HFM). While several biochemical and molecular analyses have been completed, additional biomarker measurements are ongoing. An abstract summarizing this work has been submitted for presentation at the 2025 American Society for Nutrition (ASN) annual meeting in Orlando, FL.

Publications

  • Type: Peer Reviewed Journal Articles Status: Published Year Published: 2024 Citation: Tang Y, Lin TC, Yang H, Zhou Y, Sibeko L, Liu Z. 2024. High-fat diet during early life reshapes the gut microbiome and is associated with the disrupted mammary microenvironment in later life in mice. Nutr Res. 127:1-12. doi: 10.1016/j.nutres.2024.04.006. PubMed PMID: 38763113.
  • Type: Peer Reviewed Journal Articles Status: Accepted Year Published: 2024 Citation: Lin T, Daddi L, Tang Y, Zhou Y, Liu B, Moore MD, Liu Z. 2024. Antrodia camphorata Supplementation during Early Life Alters Gut Microbiota and Inhibits Young-Onset Intestinal Tumorigenesis in APC(1638N) Mice Later in Life. Nutrients. 6(15). doi: 10.3390/nu16152408. PubMed PMID: 39125288.


Progress 03/01/23 to 02/29/24

Outputs
Target Audience:? Throughout the reporting period from March 1, 2023, to February 29, 2024, this project facilitated research training for a cohort consisting of two graduate students (one pursuing a master's degree and the other a PhD) alongside one undergraduate student. Collaborating closely, they delved into biochemical and molecular assays aimed at analyzing samples derived from our animal study focusing on the effects of a Western-style diet supplemented with mushrooms. Their efforts primarily centered around characterizing gut health. Notable completed assays encompassed gut microbiome sequencing, inflammatory cytokine profiling, and assessments of gut barrier functions. Through hands-on involvement in these tasks, the students gained valuable experience and training in the field of biomedical research. The target audience who may benefit from my project activities through our publications and presentations on professional conferences include students, research scientists, registered dietitians, nutritional professionals, and general communities who are interested in nutrition and health. We published one article (Lin TC et al 2023. Front Pharmacol. PMID: 37663253) and gave one presentation on ASN annual meeting, Nutrition 2023, Boston, MA. Changes/Problems:In our original proposal, we proposed to test the improvement of gut health by incorporating oyster mushroom into Western-style diet. Due to challenge to obtain UVB-treatment oyster mushroom powder. We switched to shiitake mushroom. Both oyster and shiitake are effective in vitamin D-production via UVB treatment, and have similar profile of other nutrients, such as fiber. In addition, both of them are produced in US and commonly consumed by US population. Therefore, the ultimate goal of this project were not changed. What opportunities for training and professional development has the project provided?As described in the "Target Audiences" section, in this reporting year, this USDA grant provided support for reach training for 2 graduate students (1PhD and 1 master) and 1 undergraduate student. Through hands-on involvement in these tasks, the students gained valuable experience and training in the field of biomedical research. How have the results been disseminated to communities of interest?Through our publications and presentations on professional conferences include students, research scientists, registered dietitians, nutritional professionals, and general communities who are interested in nutrition and health benefit from our project activities. What do you plan to do during the next reporting period to accomplish the goals?Currently, we are on the extension period of this project. The initiation of this project dates back to March 1, 2022, when I welcomed a Ph.D. student to contribute to its endeavors. Unfortunately, this student declined our department offer at the last moment. I had to reassign this project to a master student in 2022. In 2023, I successfully recruited a new PhD student who is currently responsible for experiments of this project entirely. We will continue the work as described above. We are inspired by our preliminary data from the animal study with mushroom intervention, we expect to complete the abovementioned assays in the extension year, and plan to propose human intervention studies to further develop dietary strategies to improve the quality of Western-style diet for gut health by leveraging the distinctive nutritional properties of mushrooms.?

Impacts
What was accomplished under these goals? 1. We have completed an in vitro study to investigate how a unique bacterial strain, Turcibactor, metabolizes a medicinal mushroom and thereby exerts anti-inflammatory and anti-cancer properties. The study demonstrated the specific medicinal mushroom, Antrodia camphorate, effectively suppressed the tumorigenic serotonin and Wnt-signaling pathways, and promotes ROS mediated apoptosis in Caco-2 cells. These processes are further enhanced by Turicibacter fermentation (as shown in our publication and conference presentation in the "Producs" section). 2. A animal feeding study with 4 groups: low fat control diet (LF, 10 kcal% from fat), high fat Western-style diet (HF, 45 kcal% from fat), and LF and HF supplemented with or without ultraviolet light-treated Shiitake mushroom (LFM and HFM, 5%) were completed, and biochemical and molecular analysis are undergoing. 3. In addition, this project also partially supported us to complete another scientifically related project to understand how high fat Western-style diet mechanistically mediates gut-breast axis and thereby alters mammary microenvironment. A research article has been published as shown in the "Other Products" section.

Publications

  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Lin TC, Soorneedi A, Guan Y, Tang Y, Shi E, Moore MD, Liu Z. 2023. Turicibacter fermentation enhances the inhibitory effects of Antrodia camphorata supplementation on tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells. Front Pharmacol. doi: 10.3389/fphar.2023.1203087. PMID: 37663253
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Lin TC, Guan Y, Tang Y, Moore MD, Liu Z. 2023. Conditioned medium of Turicibacter cultured with Antrodia Camphorata polysaccharide inhibits tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells. Nutrition 2023, American Society for Nutrition. Boston, MA. July 22, 2023


Progress 03/01/22 to 02/28/23

Outputs
Target Audience:This project started on 03/02/2022. During the current report period, we recently successfully completed the anima study of Western-style diet supplemented with mushroom. The biochemical and molecular assays are undergoing and the data has not been completely generated for scientific presentation and publication. In this reporting period, this project provided research training for two graduate students (1 master and 1 PhD). They worked together to get the animal feeding study successfully completed. Changes/Problems:There are no major changes/problems. In our original proposal, we proposed to test the improvement of gut health by incorporating oyster mushroom into Western-style diet. Due to challenge to obtain UVB-treatment oyster mushroom powder. We switched to shiitake mushroom. Both oyster and shiitake are effective in vitamin D-production via UVB treatment, and have similar profile of other nutrients, such as fiber. In addition, both of them are produced in US and commonly consumed by US population. Therefore the ultimate goal of this project were not changed. What opportunities for training and professional development has the project provided?As described in the "Other Products" section, in this reporting year, in this reporting period past year, this USDA grant provided support for reach training for 2 graduate students (1PhD and 1 master). These students finished their IACUC training and completed the animal feeding of the study in 2022.? How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?1.To elucidate the biological functions of the metabolites from Turicibacter culture, especially its regulatory role of inflammatory response. 2. We have completed the animal feeding study, our next step is to analyze the samples collect and thereby to examine the effect of incorporating mushroom into Western-style diet on reshaping the gut microbiome towards improving gut health, especially the combinational impact on Turicibacter-serotonin interaction.

Impacts
What was accomplished under these goals? 1. We have purchased a strain of Turcibactor from DSMZ, Germany (Turicibacter sanguinis, DSM#14220), and optimized the anaerobic microbial culture. The metabolite profile of this strain were characterized. 2. A animal feeding study with 4 groups: low fat control diet (LF, 10 kcal% from fat), high fat Western-style diet (HF, 45 kcal% from fat), and LF and HF supplemented with or without ultraviolet light-treated Shiitake mushroom (LFM and HFM, 5%) were completed. 3. In addition, this project supported us to complete another scientifically related project to understand how high fat Western-style diet mechanistically mediates gut health (intestinal tumorigenesis). A manuscript is under finalization for submission as described in the "Other Products" section.

Publications