Progress 05/01/20 to 04/30/24
Outputs
Target Audience:The target audience during this reporting period is to students, nutrition professionals, and the public/lay persons. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Due to the COVID-19, there were a lot of delays in recruiting participants and student workers. In this funding period, the following students participated in this research, including Siauyen Wong (MS, graduated May 2022), Peiran Lu (PhD, graduated in May 2022), MD Salahuddin (postdoc, 10/2022-9/2023) and MD Hasan (PhD student, Jan. 2023-Dec. 2023), and Yashu Tang (PhD student, Jan. 2023-Dec. 2023). Three undergraduates (Nathan Chaffin, Sam Ruiz, Sibble Zhang,and Jordyn Glover) completed research lab training/shadowing. Jordyn Glover also received her Wentz Scholar award 2023. Shelley Lin, a trainee from Stillwater High School Student, conducted some organoid research and awarded the prestigious Fleming Scholar at OMRF 2024. How have the results been disseminated to communities of interest?Part studies were shared with the public in the past years., , entitled Colorful foods and health, June 27, 2022. I also gave talks to multiple institutions in the United States and professional conferences. Dingbo Lin. Carotenoids: More than meet the eye, Department of Nutrition and Food Sciences, Texas Woman's University, April 12, 2024. Invited speaker. Gabrielle Glime, Daniel Frank, Lilian Berman, Nancy F. Krebs, Dingbo Lin, Minghua Tang. 2024. Gut microbiome composition, but not diversity, changed with high-astaxanthin salmon consumption in adults with obesity and prediabetes. Nutrition 2024 Yashu Tang, Dingbo Lin. 2024. Single-cell atlas of mouse ileal mucosa reveals the significance of BCO2 in the gut-lung axis and virus infection. FASEB SRC Gastrointestinal Tract XXI: Life ,Death, and Disease 09/08/24-09/12/24, Banfff, Canada Yashu Tang, MD Hasan, MD Salahuddin, Winyoo Chowanadisai, Edralin Lucas, Minghua Tang, Dingbo Lin. 2024. Astaxanthin regulates gene expression in mouse small intestinal organoids in culture. Nutrition 2024 Dingbo Lin. Carotenoids: More than meet the eye, Department of Molecular and Structural Biochemistry, North Caroline State University, March 21, 2024. Invited speaker. Dingbo Lin. Carotenoid metabolism in health and disease: A brief update. North America Chinese Association for Nutrition (NACAN) Webinar Series, April 26, 2024. Invited speaker. Dingbo Lin. Food bioactive compounds in prevention of human chronic diseases. The 14th International Conference on Functional Foods. Qingdao, China. March 29-31, 2024. Invited speaker. Dingbo Lin. Carotenoid metabolism: the good, the bad, and the ugly. University of Colorado Anschutz Medical Campus Department of Pediatrics NORC Seminar. October 12, 2023 Dingbo Lin. Dietary carotenoids in energy metabolism and blood glucose control. The 14th Asian Congress of Nutrition. Chengdu, China, September 14-17, 2023 (invited speaker-Alternative ONLINE attendance) Dingbo Lin. Carotenoid metabolism in mitochondrial function and blood glucose control. Department of Biochemistry and Microbiology Seminar, OSU CHS-Tulsa, September 1, 2023 Dingbo Lin. Carotenoid metabolism in glycemic control. Cardiovascular & Metabolic Sciences Seminar Series , Cleveland Clinic Lerner Research Institute, July 21, 2023 Dingbo Lin. Carotenoid metabolism and gut microbiome in obesity and diabetes. The 2nd International INTERACT Symposium on One Health & One Medicine. McKnight Center, Stillwater, OK, July 10-11, 2023 (invited speaker) Peiran Lu, Kevin Quinn, Michael Armstrong, Lauren E. O'Connor, Lillian M. Berman, Nichole Reisdorph, Wayne W Campbell, Nancy F. Krebs, Dingbo Lin, Minghua Tang. 2022. Intake of salmon fillets elevates plasma astaxanthin levels in human subjects. Nutrition2022 (Online)(Oral presentation) Dingbo Lin. Dietary carotenoids in immune system function. OSU Honors Symposium on Faculty Research. April 19, 2021 (Zoom, 6:30-7:30 PM) Dingbo Lin. The beauty of carotenoids: from mitochondrial function to innate immunity. University of Colorado Anschutz Medical Campus Department of Pediatrics Nutritional Science Seminar. April 1, 2021 Dingbo Lin. Nutrition update, August 20th, 9:00-10:00, Talk entitled "Nutrition and COVID19" (State Extension Program) (16 participants), 2021 Dingbo Lin. Nutrition update, July 16th, 9:00-10:00, Talk entitled "Nutrition, inflammation, and chronic disease prevention" (State Extension Program)(21 participants), 2021 Aimee K Sutliffab, Lauren O'Connore, Audrey E Hendricks, Minghua Tang, Kevin Quinn, Katrina A Doenges, Jennifer F Kemp, Jamie Westcott, Sarah J Borengasser, Richard M Reisdorph, Daniel N Frank, Dingbo Lin, Nichole A Reisdorph, Wayne W Campbell, Nancy F Krebs. Astaxanthin levels are higher in fresh salmon compared to canned and pouch varieties. Nutrition2020 (Online) Lei Wu, Yi Lyu, Brenda J Smith, Edralin Lucas, Stephen Clarke, Tyrrell Conway, Dingbo Lin. Astaxanthin metabolism shifts the gut microbiome in regulation of inflammation and metabolic homeostasis. Molecular Mechanisms Linking the Microbiome and Human Health-2020 Miami Winter Symposium. Miami, FL, January 26-29, 2020 What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
There are two major parts of this project in collaboration with Dr. Minghua Tang, University of Colorado Anschutz Medical Campus. Dr. Tang and team completed the human clinical feeding studies. Studies on mouse feeding with astaxanthin and tissue cultures were performed at Oklahoma State University. During this funding period (3 years plus 1 year NCE), we published xxx abstracts, 3 peer reviewed papers, 2 manuscripts under review, 2 manuscripts in preparation for submission, and a few presentations to the public. The major findings and results are highlighted below: In the human clinical feeding study, we recruited 28 participants with obesity and prediabetes who completed the cross over feeding experiments Thirty-one participants completed the study (n=9 male, n=19 female, n=2 not reported) with 74% Caucasian and 68% identified as non-Hispanic. The average age and BMI were 43±11.5 y and 30.3±4.3 kg/m2, respectively. Overall, participants consumed 80% of prescribed salmon and compliance did not differ between the farmed vs. wild-caught interventions. Consuming farmed salmon did not change gut microbial composition or diversity over time. When consuming wild caught salmon, no effect of time was observed on alpha diversity, but a nominal effect of time was detected on gut microbial composition (P=0.04). Specifically, the abundance of Eggerthellaceae, which may have potential anti-inflammatory effects, increased over time. Cytokines in those human plasma samples were analyzed via Bio-Plex, confirming that salmon feeding decreased inflammatory cytokines levels. Astaxanthin, as one of bioactive compounds in salmon fillets, was also used in the in vivo mouse feeding experiments and ex vivo ileal organoid cultures. The results showed that deletion of BCO2 in the Leptin receptor knockout mice (e.g., BCO2/db/db double knockout mice) made those animals more susceptible to diabetes (published in Free Radical Medicine and Biology). Feeding of astaxanthin caused significant astaxanthin accumulation and improved (decreased) fasting blood glucose levels in all mice with BCO2 depletion, e.g., BCO2 single knockout and BCO2/db/db double knockout. Simultaneously, IL-1beta, IL-6, and TNF-alpha were all decreased in mousr sera and intestinal tissues lysates, suggesting that astaxanthin was protective in inflammation and diabetes in mice. With Support from Dr. Kristin Kuhn, Director of the Gnotobiotics core facility at University of Colorado Anschutz Medical Campus, we also conducted the fecal microbiome transplant studies, using fecal samples from wild type, BCO2 KO, and BCO2/db/db double knockout mice. The studies confirmed that elevation of fasting blood glucose in those knockout mice was partially caused by the altered microbiome composition, particularly, elevation of Mucispirillum schaedleri and a decrease in Akkermansiaa muciniphila. A pilot study was added to the project about establishment of ex vivo organoid culture system and validation of astaxanthin in mucosal integrity and regeneration. This work was presented in the Nutrition 2024 Conference. The results revealed that astaxanthin can differentially regulate gene expression in the intestinalepithelial organoid cultures, especially in those derived from BCO2 KO mice. Astaxanthin-treated KO organoids exhibited enrichment of the Wnt signaling pathway, as well as increased gene transcription of hairy and enhancer of split 1 (Hes1), a key player in the Notch signaling pathway. In other words, astaxanthin affects mucosal regeneration. Building a pipeline of single cell RNA sequencing (scRNA seq) using mouse ileal mucosal tissues: we completed scRNA seq sample data analyses and will present our findings in the FASEB summer research conference 2024. Onme manuscript is being submitted to the Journal of Nutrition (under review).
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2023
Citation:
Dingbo Lin, Denis M Medeiros. The microbiome as a major function of the gastrointestinal tract and its implication in micronutrient metabolism and chronic diseases. Nutr Res. 2023 (in press). https://doi.org/10.1016/j.nutres.2023.02.007
- Type:
Journal Articles
Status:
Under Review
Year Published:
2024
Citation:
Yashu Tang, Peiran Lu, Winyoo Chowanadisai, Brenda J Smith, Edralin A. Lucas, Janeen L. Salak-Johnson, Stephen L. Clarke, Dingbo Lin. 2024. Single-cell atlas of the mouse small intestine distinguishes the significance of vitamin A and carotenoid metabolism in mucosal integrity and immunity. Journal of Nutrition (under review)
- Type:
Journal Articles
Status:
Under Review
Year Published:
2024
Citation:
Peiran Lu, Nichole Reisdorph, Richard Reisdorph, Kevin Quinn, Michael Armstrong, Cole Michel, Katrina Doenges, Daniel N. Frank, Audrey E. Hendricks, Wayne W Campbell, Emily B. Hill, Nancy F. Krebs, Yashu Tang, Dingbo Lin, Minghua Tang. Characterization of astaxanthin isomers in different types of salmon filets and human plasma after salmon consumption. Food Chemistry (under review)
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Progress 05/01/22 to 04/30/23
Outputs
Target Audience:The target audience during this reporting period is students, nutrition professionals, and the public/lay persons.? Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Due to the COVID-19, there were a lot of delays in recruiting participants and student workers. In this funding period, the following students participated in this research, including Siauyen Wong (MS, graduated May 2022), Peiran Lu (PhD, graduated in May 2022), MD Salahuddin (postdoc, 10/2022-9/2023) and MD Hasan (PhD student, Jan. 2023-Dec. 2023), and Yashu Tang (PhD student, Jan. 2023-Dec. 2023). Three undergraduates (Nathan Chaffin, Sam Ruiz, Sibble Zhang,and Jordyn Glover) completed research lab training/shadowing. Jordyn Glover also received her Wentz Scholar award 2023. How have the results been disseminated to communities of interest?Part studies were shared with the public in the past years., , entitled Colorful foods and health, June 27, 2022. I also gave talks to multiple institutions in the United States and professional conferences. Peiran Lu, Kevin Quinn, Michael Armstrong, Lauren E. O'Connor, Lillian M. Berman, Nichole Reisdorph, Wayne W Campbell, Nancy F. Krebs, Dingbo Lin, Minghua Tang. 2022. Intake of salmon fillets elevates plasma astaxanthin levels in human subjects. Nutrition2022 (Online)(Oral presentation) What do you plan to do during the next reporting period to accomplish the goals?Working on manuscript writing and publishing the findings in peer-review journals.
Impacts
What was accomplished under these goals?
There are two major parts of this project in collaboration with Dr. Minghua Tang, University of Colorado Anschutz Medical Campus. Dr. Tang and team completed the human clinical feeding studies. Studies on mouse feeding with astaxanthin and tissue cultures were performed at Oklahoma State University. During this funding period (3 years plus 1 year NCE), we published xxx abstracts, 3 peer reviewed papers, 2 manuscripts under review, 2 manuscripts in preparation for submission, and a few presentations to the public. The major findings and results are highlighted below: In the human clinical feeding study, we recruited 28 participants with obesity and prediabetes who completed the cross over feeding experiments Thirty-one participants completed the study (n=9 male, n=19 female, n=2 not reported) with 74% Caucasian and 68% identified as non-Hispanic. The average age and BMI were 43±11.5 y and 30.3±4.3 kg/m2, respectively. Overall, participants consumed 80% of prescribed salmon and compliance did not differ between the farmed vs. wild-caught interventions. Consuming farmed salmon did not change gut microbial composition or diversity over time. When consuming wild caught salmon, no effect of time was observed on alpha diversity, but a nominal effect of time was detected on gut microbial composition (P=0.04). Specifically, the abundance of Eggerthellaceae, which may have potential anti-inflammatory effects, increased over time. Cytokines in those human plasma samples were analyzed via Bio-Plex, confirming that salmon feeding decreased inflammatory cytokines levels. Astaxanthin, as one of bioactive compounds in salmon fillets, was also used in the in vivo mouse feeding experiments and ex vivo ileal organoid cultures. The results showed that deletion of BCO2 in the Leptin receptor knockout mice (e.g., BCO2/db/db double knockout mice) made those animals more susceptible to diabetes (published in Free Radical Medicine and Biology). Feeding of astaxanthin caused significant astaxanthin accumulation and improved (decreased) fasting blood glucose levels in all mice with BCO2 depletion, e.g., BCO2 single knockout and BCO2/db/db double knockout. Simultaneously, IL-1beta, IL-6, and TNF-alpha were all decreased in mousr sera and intestinal tissues lysates, suggesting that astaxanthin was protective in inflammation and diabetes in mice. With Support from Dr. Kristin Kuhn, Director of the Gnotobiotics core facility at University of Colorado Anschutz Medical Campus, we also conducted the fecal microbiome transplant studies, using fecal samples from wild type, BCO2 KO, and BCO2/db/db double knockout mice. The studies confirmed that elevation of fasting blood glucose in those knockout mice was partially caused by the altered microbiome composition, particularly, elevation of Mucispirillum schaedleri and a decrease in Akkermansiaa muciniphila.
Publications
- Type:
Conference Papers and Presentations
Status:
Submitted
Year Published:
2022
Citation:
2.Peiran Lu, Yashu Tang, Kelley Lin, Siau Yen Wong, Jianmin Chai, Paniz Jasbi, Lei Wu, Edralin A Lucas, Hui He, Jiangchao Zhao, Haiwei Gu, Tyrrell Conway, Adrian Wyss, Brenda J Smith, Dingbo Lin. Zeaxanthin-altered gut microbiome is associated with changes in whole body bone mineral density in mice. K-INBRE Genomics Symposium. University of Kansas-Lawrence, May 2022 (oral presentation). Other Products
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Progress 05/01/21 to 04/30/22
Outputs
Target Audience:The target audience during this reporting period is students, nutrition professionals, and the public/lay persons. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?I closely worked with the collaborators and peers and visited Dr. Minghua Tang's lab for information exchange. One Ph.D. student who was partially supported by this project was graduated in April 2022. Currently, I have one new Ph.D. who joined the project in Jan 2022. How have the results been disseminated to communities of interest?I have delivered a couple of seminars to nutrition educators in the state of Oklahoma and presented the findings at nutrition conferences. What do you plan to do during the next reporting period to accomplish the goals?Continue to work with my team members and collaborators to complete the proposed work. I plan on publishing more papers and delivering presentations to the community.
Impacts
What was accomplished under these goals?
Over the past 12 months (the year 2 of the funded project), we have made significant progress in completing both goals. The overall progress has been delayed primarily due to COVID-19 in year 1 of the funded project (May 1, 2020-April 30, 2021). We might be working on the request for a no-cost extension for an additional year. For Goal #1, Since April 2021, we have made significant progress in the clinical trial. As described in the last progress report, COVID delayed the onset of the study due to the mandatory shut down of all non-emergency clinical research on the Anschutz Medical Campus and reduced the likelihood of participation of interested participants. Our team has worked diligently to recruit and retain participants over the last 12 months. In summary, we received 123 total inquiries from flyers posted on campus, in local libraries, community centers, and on research study websites. Out of the 123 inquires, 54 were ineligible (mostly due to BMI or age), 24 lost contact, and 9 were not interested (too much salmon, too much involvement/didn't work with schedule, or didn't give a reason). Our study coordinator is still working with eight potentially interested and eligible people. Currently, we have 28 subjects who consented and 6 dropped out of the study due to various reasons. Table 1 (next page) summarized the timeline of the enrolled participants. We expect to finish recruitment by the end of August and sample analysis will start in fall of 2022. For Goal #2, we successfully completed astaxanthin feeding study in wild-type, BCO2 knockout (KO), db/db, and BCO2/db/db double knockout (DKO) mice. All mice were produced from the heterozygous breeders (BCO2 het/db/db het). Animals were fed a 0.04 % Astaxanthin diet for 8 weeks, chow diet was used as a negative control. Feces, blood samples, and tissues (colon, small intestines, and liver) were collected and stored properly for further analysis. Fecal transplant into germ-free mice (GFM) had/has been performed in Dr. Kristine A Kuhn's Gnotobiotics Core at the University of Colorado Anschutz Medical Campus. C57BL/6J GFM baseline controls (9 males and 10 females at 11 weeks of age) and GFM transplanted with chow-diet fed BCO2/db/db fecal microbiome (8 males and 9 females at 11 weeks of age) had been accomplished. We are working on transplanting fecal microbiome from the BCO2/db/db mice fed with the astaxanthin group. Samples analyses are performed in year 3. Figure 1 shows that BCO2 and db/db double knockout mice were hyperglycemia, particularly their fasting blood glucose (FBG) levels were elevated significantly after 10 weeks of age (DKO-P group in Fig. 1). However, supplementation of astaxanthin diet significantly diminished the elevation of FBG in the DKO-A group, suggesting the preventive effect of accumulated astaxanthin on FBG in diabetic mice. We also found that astaxanthin feeding decreased inflammatory cytokine levels in DKO-A group, compared to DKO-P (a placebo group). We are working on other biochemical and microbiome and metabolomics analyses in year 3.
Publications
- Type:
Journal Articles
Status:
Accepted
Year Published:
2021
Citation:
Lei Wu, Peiran Lu, Xin Guo, Kun Song, Yi Lyu, James Bothwell, Jinglong Wu, Olivia Hawkins, Stephen L. Clarke, Edralin A. Lucas, Brenda J. Smith, Winyoo Chowanadisai, Steve Hartson, Jerry Ritchey, Weiqun Wang, Denis Medeiros, Shitao Li, Dingbo Lin. 2021. ?-carotene oxygenase 2 deficiency-triggered mitochondrial oxidative stress promotes inflammation and metabolic disorders. Free Radical Biology Medicine. https://doi.org/10.1016/j.freeradbiomed.2021.01.003
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2021
Citation:
Peiran Lu, Siau Yen Wong, Jianmin Chai, Lei Wu, Brenda J Smith, Edralin A Lucas, Stephen L Clarke, Winyoo Chowanadisai, Hui He, Jiangchao Zhao, Tyrrell Conway, Adrian Wyss, Dingbo Lin. 2021. Xanthophylls shift the gut microbiota and reduce inflammation during influenza A virus infection. Nutrition2021 (Online)
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2021
Citation:
Peiran Lu, Siau Yen Wong, Jianmin Cha, Paniz Jasbi, Lei Wu, Yi Lyu, Minghua Tang, Brenda J Smith, Edralin A Lucas, Stephen L Clarke, Winyoo Chowanadisai, Xinchun Shen, Hui He, Jiangchao Zhao, Haiwei Gu, Tyrrell Conway, Adrian Wyss, Dingbo Lin. 2021. Zeaxanthin drives dynamic changes in the mouse metabolome through gut microbiome shift. Nutrition2021 (Online)
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Progress 05/01/20 to 04/30/21
Outputs
Target Audience:The target audience during this reporting period is students, nutrition professionals, and the public/lay persons. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?During the reporting period, I have communicated with my peers, had collaborations with other institutes, and trained a couple of graduate students. How have the results been disseminated to communities of interest?I have done several presentations in nutrition and had related meetings while also publishing the results in scientific journals. What do you plan to do during the next reporting period to accomplish the goals?Work will continue as originally proposed with students, collaborators, and other peers in the proposed research. I plan to publish more papers and deliver presentations to the community.
Impacts
What was accomplished under these goals?
We have made great progress over the past 12 months, albeit with the many challenges we faced with COVID. Due to COVID, Oklahoma State University partially locked down the lab research capacities for practicing social distancing, and the University of Colorado shut down all clinical research activities from March to July 2020. For Goal #1, We were still able to submit the IRB application in June 2020 and received IRB approval in August 2020. We also obtained other regulatory compliance approval, including clinicaltrials.gov and OnCore approvals in September 2020. After obtaining the approvals, we worked together with the Clinical & Translational Research Center (CTRC) at the University of Colorado and obtained salmon samples from different vendors. We tested astaxanthin and fatty acid profiles in both wild-caught and farmed salmon samples. In brief, we followed the procedure of published studies and used dry ice blending to process 12 salmon fillets (3 Wild Raw, 3 Wild Cooked with no Oil, 3 Farmed Raw, 3 Farmed Cooked with no Oil). GC-MS eas used to target fatty acids, esterified fatty acidsand non-esterified fatty acids. LC-MS QTOF untargeted Lipid analysis with Targeted Astaxanthin extraction and additional MSMS analysis was performed to identify and quantify Astaxanthin. In brief, Astaxanthin was significantly higher in wild-caught salmon vs. farmed salmon, with great consistency between fishes. These findings reassured our approach of comparing wild- vs. farmed salmon with different astaxanthin content on inflammation and gut microbiota is valid. These analyses were conducted in October and November of 2020. In November 2020, due to the significant increase in COVID cases in the metro Denver area, the University of Colorado issued a new restriction and only allowed virtual research activities to continue. This restriction was lifted in mid-Jan 2021. Per CTRC's requirement, we submitted a request to re-activate our IRB protocol abiding by all COVID regulations. This reactivation requested was approved in Feb 2021. After purchasing in bulk of the wild and farmed salmon, we are only recently ready to recruit participants. We haven't had anyone enrolled in the study yet but expect to see a steady enrollment number soon. For Goal #2, we had been successfully received the approval of IACUC protocol and initiated the astaxanthin feeding study in wild type, BCO2 knockout (KO), db/db, and BCO2/db/db double knockout (DKO) mice. All mice were produced from the heterozygous breeders (BCO2 het/db/db het). Genotyping was performed by Transnetyx, Inc. Animals were fed 0.04 % Astaxanthin diet for 8 weeks, chow diet was used as a negative control. Feces, blood samples, and tissues (colon, small intestines, and liver) were collected and stored properly for further analysis. Fecal transplant into germ-free mice will be conducted in late summer, 2021.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Lei Wu, Yi Lyu, Ramkumar Srinivasagan, Jinlong Wu, Babajide Ojo, Minghua Tang, Guadalupe Davilla El-Rassi, Katherine Metzinger, Brenda J Smith, Edralin A Lucas, Stephen L Clarke, Winyoo Chowanadisai, Xinchun Shen, Hui He, Tyrrell Conway, Johannes von Lintig, Dingbo Lin. 2020. Astaxanthin-shifted gut microbiota is associated with inflammation and metabolic homeostasis in mice. J Nutr. 2020 Oct 12;150(10):2687-2698. doi: 10.1093/jn/nxaa222.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2020
Citation:
Aimee K Sutliffab, Lauren OConnore, Audrey E Hendricks, Minghua Tang, Kevin Quinn, Katrina A Doenges, Jennifer F Kemp, Jamie Westcott, Sarah J Borengasser, Richard M Reisdorph, Daniel N Frank, Dingbo Lin, Nichole A Reisdorph, Wayne W Campbell, Nancy F Krebs. Astaxanthin levels are higher in fresh salmon compared to canned and pouch varieties. Nutrition2020 (Online)
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