Browsing by Author "Lucas, Edralin"
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Item Dietary Supplementation With Montmorency Tart Cherries and Exercise Improves Lean Mass in Older C57BL/6 Mice(Elsevier, 2021) Robinson, Kara; Hatter, Bethany; Washburn, Karley; Bothwell, James; Anderson, Kendall; Lin, Dingbo; Lucas, Edralin; Smith, Brenda; Obstetrics and Gynecology, School of MedicineObjectives: Sarcopenia, the progressive loss of muscle mass and strength, accelerates with age. Current recommendations to prevent sarcopenia focus on exercise and protein intake. Tart cherry (TC) has shown beneficial effects on muscle recovery following exercise. In this study, we investigated the effects of TC alone and in combination with exercise on lean mass, mitochondrial biogenesis, and oxidative stress in young compared to older mice. Methods: In two cohorts (6 & 52 wk-old), female C57BL/6 mice were randomly assigned to 4 groups in a 2 × 2 factorial design with diet (AIN-93 control or TC supplemented at 10% w/w) and exercise as factors. Exercise consisted of treadmill running for 30 min, 5 d/wk, at 12 m/min and a 5° incline. Food intake was recorded daily and body weights weekly. After 8 wks, body composition was assessed using dual-energy x-ray absorptiometry. The gastrocnemius muscle was collected for protein analysis. Western blotting techniques were used to probe for superoxide dismutase 2 (SOD2) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1a), indicators of oxidative stress and mitochondrial biogenesis. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control. Data were analyzed using 2-way ANOVA with α = 0.05. Results: In young mice, TC had no effect on body weight and % lean mass, but led to decreased (P < 0.05) % fat mass compared to controls. Exercise decreased (P < 0.05) body weight and % fat, and tended to increase (P = 0.069) % lean mass. In contrast, TC and exercise independently decreased body weight and % fat, and increased % lean mass in older mice compared to controls. The combination of TC and exercise tended to have a synergistic effect on % lean mass (P = 0.056). Preliminary results show that TC significantly up-regulated SOD2 protein expression in young mice, but no effect was observed with exercise or combined treatments. PGC1α expression tended to be suppressed (P = 0.064) in young animals fed TC. To date, we have been unable to detect changes in SOD2 and PGC1α in older mice. Conclusions: TC had a protective effect on lean tissue in older mice, preliminary analyses revealed no alterations in oxidative stress or mitochondrial biogenesis. Further investigation is warranted to understand the benefits of TC on lean muscle mass in older mice.Item Differential Effects of the Polyphenols and Carbohydrates in Dried Plum Account for the Fruit’s Benefits on Bone Health in Estrogen Deficiency(Elsevier, 2021) Hatter, Bethany; Washburn, Karley; Graef-Downard, Jennifer; Crokett, Erica; King, Jarrod; Cichewicz, Robert; Lucas, Edralin; Smith, Brenda; Obstetrics and Gynecology, School of MedicineObjectives: This study investigated the effects of dried plum’s (DP) polyphenols (PP) and carbohydrates (CHO) on bone mass, microarchitecture, and biomarkers of metabolism over time in an osteopenic model of estrogen deficiency. Methods: A 2 × 2 factorial (factors CHO & PP) embedded within a randomized block design was used with 3-m old C57BL/6 female mice, sham-operated (Sham = 2 groups) and fed AIN-93M control diet (Con) or ovariectomized (OVX = 10 groups) and fed Con or Con diet supplemented with DP (25% w/w), a comparable dose of crude PP extract (CPE), fractionated CHO or PP extract for 5 or 10 wks. At each end-point, dual-energy x-ray absorptiometry scans were performed and bone microarchitecture was assessed at the femur and lumbar vertebra using micro-computed x-ray tomography. Serum biomarkers of osteoblast activity, procollagen type 1 N-terminal propeptide (P1NP), and osteoclast activity, tartrate-resistant acid phosphate (TRAP) were assayed using EIAs. Data was analyzed using SAS with effects of DP and CPE examined using 1-way ANOVA and effects of PP and CHO examined using a 2-way ANOVA. Results: At 5 and 10-wks, mice on the DP and CPE diets had higher (P < 0.05) whole body bone mineral density (BMD), content (BMC), trabecular bone volume (BV/TV) and number (TbN) in the vertebrae and femur compared to the OVX-Con. By 10 wks, improvements in trabecular bone with DP and CPE were greater (P < 0.05) than Sham. Only the CPE significantly improved cortical thickness, a response observed at only 5 wks. DP and CPE had no effect on P1NP, but suppressed OVX-induced increase in TRAP at 5 and 10 wks. PP and CHO increased (P < 0.05) whole body BMD and BMC. CHO significantly improved trabecular BV/TV, TbN, separation, connectivity density, and structure model index at both time points. A similar response occurred in vertebral trabecular bone. In contrast, cortical thickness was increased (P < 0.05) with CHO at 5 wks, but by 10 wks PP alone and in combination with CHO accounted for improved cortical area, thickness and porosity. CHO suppressed TRAP at both time points, but P1NP only at 5 wks. PP did not alter P1NP and only when combined with CHO suppressed TRAP at 5 wks. Conclusions: In the OVX model, both the CHO and PP of DP positively affect BMD, with the CHO fraction enhancing trabecular bone and the PP fraction improving cortical bone.Item Interleukin (IL)-10 Is Important in the Maintenance of Trabecular and Cortical Bone and Protects Against Western Diet-Induced Disruption in Bone Remodeling in Mice(Elsevier, 2021-06-07) Perez, Leo; Alake, Sanmi; Price, Payton; Islam, Proapa; Ice, John; Lucas, Edralin; Smith, Brenda; Obstetrics and Gynecology, School of MedicineObjectives: The purpose of this study was to investigate if consumption of a western diet (WD) exacerbates the effects of loss of function of IL-10, an anti-inflammatory cytokine, on biomarkers of bone metabolism and microarchitecture. Methods: Six-week-old male B6.129P2-Il10tm1Cgn/J (IL-10 KO) and C57BL/6 mice (WT) were randomized to treatment in a 2 × 2 factorial with diet (AIN-93 control diet CD vs WD) and strain (IL-10 KO vs WT) as factors. Due to potential influence of high fat on intestinal Ca absorption, a WD diet with added Ca (1.2 g/kg) was used. After 12 wks, whole body dual-energy x-ray absorptiometry scans were performed to assess bone density and body composition, and micro-computed x-ray tomography was used to evaluate trabecular and cortical bone microarchitecture in the femur and lumbar vertebra. Serum biomarkers of bone formation, procollagen 1 intact N-terminal propeptide (P1NP), and resorption, c-terminal telopeptide of type I collagen (CTX-1) were assessed. Results: Body weight, but not % body fat, was lower (P < 0.05) in IL-10 KO mice relative to WT controls. 12 weeks of WD increased (P < 0.05) body weight and % fat, but the response was not as great in the IL-10 KO mice. Bone mineral density and content were lower in IL-10 KO mice compared to WT, and the WD had no effect on these parameters. The IL-10 KO mice exhibited a decrease in trabecular bone volume, thickness, and number, and an increase in trabecular separation and structure model index compared to WT mice within the femur and vertebrae. The WD had no effect on these trabecular bone parameters. Cortical bone thickness and area were reduced (P < 0.05) and porosity increased in both the femur and vertebra of IL-10 KO mice relative to their WT counterparts. This strain effect was not altered by the WD. IL-10 KO mice exhibited a significantly lower serum PINP and higher CTX-1 compared to the WT mice. Despite the lack of structural changes in bone after 12 wks, the WD increased (P < 0.05) CTX-1 and tended to suppress P1NP (P = 0.051) in the IL-10 KO mice compared to WT. Conclusions: We conclude that IL-10 plays an important role in bone metabolism and maintaining structural properties and in the absence of IL-10, WD negatively affects both osteoclast and osteoblast activity. Further studies are warranted to determine if structural changes occur with longer exposure to WD.Item Loss of Interleukin (IL)-10 Is Associated With Increased Vascular Inflammation and Sex-Differences in Metabolic Outcomes of Normal Diet-Fed Mice(Elsevier, 2021) Alake, Sanmi; Ojo, Babajide; Kaur, Amritpal; Hermann, Evan; Ice, John; Chowanadisai, Winyoo; Lin, Dingbo; Smith, Brenda; Lucas, Edralin; Obstetrics and Gynecology, School of MedicineObjectives: The anti-inflammatory cytokine, IL-10, plays an important role in reducing the risk of many inflammatory diseases. This study investigated the time and sex effects of IL-10 gene deletion on metabolic risk factors that contribute to the development of cardiovascular disease. Methods: Six-wk-old male and female B6.129P2-Il10tm1Cgn/J (IL-10–/–) and C57BL/6 (WT) mice (n = 12–16/group) were randomly assigned to 12- or 24-wk time points and were fed growth (AIN-93G) diet up to 3 m of age and then maintenance diet (AIN-93M) for the remainder of the study. Monthly fasting glucose was assessed as well as intraperitoneal glucose tolerance test (ipGTT), body composition, and serum metabolic parameters at each study end point. Cardiac and vascular adhesion molecules, macrophage marker F4/80, and sterol metabolism genes were assessed using qPCR. Data were analyzed using t-test and 2-way ANOVA with strain and gender as factors, and α = 0.05. Results: IL-10 deletion resulted in weight loss (p < 0.05) coinciding with reduced fat mass and % fat (P < 0.05) in both sexes of IL-10–/–. Loss of IL-10 had no effect on fasting glucose at any time point in either sex; however, a delayed response to glucose challenge and increased AUC with the ipGTT (P < 0.05) occurred in male IL-10–/– vs WT mice. No strain effect was observed on serum lipids at 12 wks, but cholesterol and high-density lipoprotein (HDL)-C were reduced (P < 0.05) in IL-10–/– vs WT mice at 24 wks. Only male IL-10–/– mice exhibited elevated (P < 0.05) non-HDL cholesterol and tended (P = 0.072) to have elevated triglycerides vs WT mice at 24 wks. In conjunction with serum lipid changes, male IL-10–/– mice increased (P < 0.05) hepatic transcription of β-hydroxy β-methylglutaryl-CoA (HMG-CoA), whereas HMGCoA transcript tended to be repressed (≥ –53.5%; P = 0.08) in female IL-10–/– vs WT mice. At 12 and 24 wks, IL-10–/– exhibited increased (P < 0.05) circulating c-reactive protein and aortic and cardiac gene expression of VCAM-1, ICAM-1, and iNOS. The only increase in the F4/80 macrophage marker occurred in male IL-10–/– mice vs WT at 24 wks. Conclusions: Loss of IL-10 was associated with different metabolic responses in male and female mice and could be detrimental to cholesterol-mediated metabolic processes in female mice on a control diet.Item Montmorency Tart Cherry Supplementation Has Modest Effects on the Gut Microbiome and Markers of Gut Integrity and Insulin Resistance in Mice Fed Western Diet(Elsevier, 2021) Kaur, Amritpal; Ojo, Babajide; Wong, Siau Yen; Alake, Sanmi; Davila-El Rassi, Guadalupe; Pastor, Madison; Lin, Dingbo; Smith, Brenda; Lucas, Edralin; Obstetrics and Gynecology, School of MedicineObjectives: This study investigated the dose-dependent effects of freeze-dried Montmorency tart cherry (TC) supplementation on gut health and metabolic parameters in mice fed a western diet (WD). Methods: Six-week-old male C57BL/6 mice were randomly assigned to dietary treatment groups in a 2 × 3 factorial design with diet (control [AIN-93M] or WD, 45% fat kcal and 26% sucrose kcal) and TC (0, 5, 10% wt/wt) as factors for 12 wks. At the end of dietary treatment, body composition was assessed by dual energy xray absorptiometry, and tissues were collected to evaluate metabolic parameters and markers of gut health. Cecal content was used for bacterial and short chain fatty acid analyses (SCFAs). Results: TC at the 10% dose significantly increased the abundance of the beneficial bacterial phylum, Actinobacteria, relative to the unsupplemented groups (P = 0.018 and 0.010 vs control and WD, respectively). Relative cecal weight (P = 0.007) and SCFAs were significantly increased (P < 0.05) with TC supplementation (∼20% and 2-fold for relative cecal weight and SCFAs, respectively). Histological evaluation revealed reduced ileal villi height (P = 0.0348), width (P = 0.0042) and area (P = 0.0132) with WD, and TC did not alter this response. Overall, the expression of genes related to gut health (i.e barrier integrity marker, mucus layer formation, and inflammatory marker), were unaffected by both WD and TC supplementation. Body weight (P = 0.0012), fat mass (P = 0.007), fasting blood glucose (P = 0.001), serum total cholesterol (P < 0.0001), triglyceride (P = 0.002), leptin (P = 0.0011), plasminogen activator inhibitor 1 (P = 0.0344), and resistin (P = 0.0012) were increased with WD, and TC had no effect on these parameters. Despite modest effects on metabolic parameters, the homeostatic model assessment of insulin resistance, HOMA-IR, a commonly used tool for assessing insulin resistance, was improved by 50% with the 5% TC (P = 0.0003). Conclusions: TC supplementation restored some beneficial bacteria and increased SCFAs altered by WD. However, these changes in the gut did not translate to improvement in metabolic outcomes except for HOMA-IR. The mechanism by which TC improves HOMA-IR needs to be investigated in future studies.Item Pulse Supplementation Improves Gut Health and Lowers Total Cholesterol in Postmenopausal Women(Elsevier, 2022) Orphan, Jessica; Alake, Sanmi; Keirns, Bryant; Ice, John; Smith, Brenda; Emerson, Sam; Lucas, Edralin; Obstetrics and Gynecology, School of MedicineObjectives: Menopause is associated with many physiological changes as well as increased risk of obesity, cardiovascular disease, type 2 diabetes, and gut-related diseases (i.e. irritable bowel syndrome, inflammatory bowel disease, colon cancer). Data regarding the use of pulse crops in alleviating health risks associated with menopause are limited. This study investigated the effects of pulse supplementation on markers of gut health and metabolic outcomes in postmenopausal women. Methods: Thirty-five postmenopausal (≥1 year without menstruation) women, ages 45–70 years old, who were not on hormone replacement therapy, probiotics, antibiotics, multiple supplements, or medications that affect lipids or glucose, were recruited for this clinical study. Study participants were asked to consume 100 g of pulses (alternate between chickpeas, kidney beans, pinto beans, black-eyed peas, and lentils) daily for 12 wks, and to maintain their normal diet and lifestyle. Anthropometric measures including body composition by dual-energy X-ray absorptiometry, plasma lipids and glucose, fecal short chain fatty acids (SCFAs), and stool characteristics (Bristol Stool Chart and the Cleveland Clinic Constipation Scoring System) were assessed before and at the end of 12-wk supplementation. P < 0.05 was considered statistically significant. Results: There were no differences in anthropometric measures and plasma glucose at the end of the 12-wk supplementation compared to baseline. However, a reduction in plasma total cholesterol (p = 0.039) and LDL-C (p = 0.026), but an increase in both VLDL-C (p = 0.031) and triglycerides (p = 0.033) were observed with pulse supplementation. Constipation score significantly improved (p = 0.003) but no change in stool quality were observed with pulse supplementation. Fecal acetic acid (p< 0.001), n-butyric (p = 0.038), n-caproic (p = 0.004) and total SCFAs (p = 0.001) were also significantly increased with pulse supplementation. Conclusions: Our findings demonstrate that 12 wks of pulse supplementation improved markers of gut health and lowers total- and LDL-cholesterol in postmenopausal women. This population who are at an increased risk for cardiovascular and gut-related diseases can benefit from regularly consuming pulses.Item Understanding How Sex Influences the Impact of IL-10 on Bone Microarchitecture and Bone Metabolism Over Time(Elsevier, 2021) Price, Payton; Perez, Leo; Hatter, Bethany; Robinson, Kara; Islam, Proapa; Alake, Sanmi; Ice, John; Lucas, Edralin; Smith, Brenda; Obstetrics and Gynecology, School of MedicineObjectives: Dietary interventions with pre- and probiotics favorably affect the gut-bone axis, mediated in part by the anti-inflammatory cytokine, interleukin (IL)-10. This study sought to understand how IL-10’s impact on bone metabolism and microarchitecture differs with sex and time. Methods: Six-week-old B6.129P2-Il10tm1Cgn/J (KO) and C57BL/6 (WT) mice were assigned in a 2 × 2 × 2 factorial design with strain (WT & KO), sex, and time (3 & 6 m) as factors. Mice were fed AIN-93G diet for 3 m followed by AIN-93 M for the study duration. Dual-energy x-ray absorptiometry was used to assess bone mineral content (BMC) and density (BMD). Micro-computed tomography was used to assess femur and lumbar vertebrae trabecular and cortical bone. Serum procollagen 1 intact N-terminal propeptide (P1NP) and C-terminal telopeptide of type I collagen (CTX-1), bone formation and resorption markers respectively, were assessed by ELISA. Data were analyzed using ANOVA; p < 0.05 was considered significant. Results: Reductions in BMC and BMD (P < 0.05) in KO vs WT and at 3 vs 6 m were observed; a sex effect was found with reductions in BMC in KO females compared to KO males. Femoral trabecular bone volume (BV/TV) was lower (P < 0.05) in KO vs WT, females vs males, and at 6 vs 3 m. Trabecular thickness (TbTh) decreased (P < 0.05) in KO vs WT and increased from 3 to 6 m, while decreases in trabecular number (TbN) were greater (P < 0.05) in KO mice, females, and at 6 m compared to counterparts. Cortical area and thickness were decreased (P < 0.05) in KO vs WT and in females vs males, which was greater at 6 m, while cortical bone porosity was higher in KO vs WT and increased at 6 mo. Vertebral trabecular BV/TV was lower (P < 0.05) in KO vs WT at 3 and 6 m, with KO females showing reduced BV/TV (P < 0.05) from 3 to 6 m. Reduced TbTh and TbN were observed in KO vs WT, and females had increased (P < 0.05) TbTh and trabecular separation and reduced TbN. P1NP showed a time effect (P < 0.05) with reductions in WT females and males at 6 m compared to 3 m KO females (P < 0.05). CTX-1 shows a sex effect (P < 0.05) and a trending strain effect (P = 0.059), with elevated serum CTX-1 in 3 m KO males compared to WT and KO females at 6 m (P < 0.05). Conclusions: While IL-10 plays an important role in maintaining both trabecular and cortical bone, it may have a more protective effect on the cortical bone of female mice over time.Item Wheatgerm Supplementation Reduces Gut Inflammation and Epithelial Barrier Dysfunction in IL-10 KO Mice Fed Atherogenic Diet(Elsevier, 2022) Alake, Sanmi; Chowanadisai, Winyoo; Ice, John; Lin, Dingbo; Lucas, Edralin; Smith, Brenda; Wozniak, Karen; Obstetrics and Gynecology, School of MedicineObjectives: Wheat germ (WG) contains many bioactive compounds with the potential to maintain an anti-inflammatory gut environment. This study investigated the effects of WG supplementation on gut inflammation and integrity in high-fat fed interleukin (IL)-10 KO mice. Methods: Eight-wk-old female B6.129P2-Il10tm1Cgn/J (IL-10KO) and C57BL/6 (WT) mice (n = 10/group) were randomly assigned to diets: WT fed a control diet (WTCO; AIN93-M) and IL-10 KO mice fed control (KOCO), high-fat with high-cholesterol (HFHC; 45% fat kcal, 1% cholesterol), or HFHC + 10% WG (HFWG) for 3 m. Disease activity indices (fecal blood, ruffled fur, stool softness, and rectal prolapse) were monitored twice a week. Fecal indole and short chain fatty acids (SCFAs) concentration were assessed at the beginning and end of study. Proinflammatory cytokines were assessed in the serum and ileum. Ileal and colonic protein expression of transcription factors (STAT3, p-STAT3, PPARg, FoxP3, and AhR), tight junction proteins (ZO-1, occludin), and tryptophan catabolizing enzyme (IDO-1) were assessed by immunoblotting. Relative ileal and colonic gene expression of IL-22 and antimicrobial peptides (Reg3b and Reg3g) were assessed using qRT-PCR. P < 0.05 was considered statistically significant. Results: WG increased (P = 0.003) colon length compared to the HFHC group. Weight loss (12.2% in HFHC vs WTCO) was not prevented by WG, but disease activity indices were significantly reduced in the WG vs HFHC group. WG also increased fecal indole, total SCFAs and acetate accompanied by an increase in colonic protein expression of PPARg (P < 0.0001) and FoxP3 (P = 0.001). Ileal STAT3 phosphorylation was reduced (P = 0.0076) due to WG supplementation. An increased colon and ileal protein expression of IDO-1 in the HFHS group was reduced by WG, while also increasing the expression of AhR, ZO-1, and occludin. The relative gene expression of the antimicrobial peptides (Reg3b and Reg3g) was increased (P < 0.05) while serum and ileal tissue concentration of the proinflammatory cytokine, IL-17 was reduced (P = 0.0165 and p = 0.0248 respectively) by WG. Conclusions: WG modulated changes that are associated with HF-feeding in IL-10 KO mice, and might be a promising regimen for ameliorating the effects of gut inflammation.Item Xanthophylls Shift the Gut Microbiota and Reduce Inflammation in Mice During Influenza A Virus Infection(Elsevier, 2021) Lu, Peiran; Wong, Siau Yen; Chai, Jianmin; Wu, Lei; Smith, Brenda; Lucas, Edralin; Clarke, Stephen L.; Chowanadisai, Winyoo; He, Hui; Zhao, Jiangchao; Conway, Tyrrell; Wyss, Adrian; Lin, Dingbo; Obstetrics and Gynecology, School of MedicineObjectives: Seasonal influenza A virus (IAV) infection impacts both respiratory and intestinal microbiome homeostasis. However, it is not well understood the extent to which the gut-lung axis plays the role in innate immunity and acute inflammation during IAV. Xanthophylls are fat-soluble, oxygenized carotenoids with potent antioxidant properties. We recently reported that xanthophylls can promote gut microbiome homeostasis and is associated with attenuation of intestinal and systemic inflammation. Here, we sought to investigate the protective effects of xanthophylls, e.g., zeaxanthin (Z) and astaxanthin (A) in IAV pneumonia by regulation of the host gut microbiome. Methods: Six-week-old male and female 129S6 wild type (WT) and beta-carotene oxygenase 2 (BCO2) knockout mice were fed with AIN93M chow diets supplemented with or without Z (0.02% w/w) and A (0.02 w/w) (e.g., A + Z). After 6 weeks of the dietary intervention, mice were intranasally infected with 100 pfu H1N1 PR8 virus. Animal body weight and phenotypes were monitored daily. Animals were sacrificed 6 days post-infection. Blood and lung tissues were collected for experiments. H & E staining, gut microbiota 16S rRNA sequencing, immunohistochemistry, and immunoblotting were used for clinical, histopathological, and other biochemical assessments. Results: Depletion of BCO2, the xanthophyll cleavage enzyme, made mice more resistant to IAV infection. Administration of A + Z caused A + Z accumulation and enhanced resistance to IAV in BCO2 KO but not WT mice, as demonstrated by histological lung damage and colon and ileum inflammation. Gut microbiome profiling results showed that α–diversity and β–diversity were significantly altered in these experimental groups. In particular, A + Z accumulation is positively associated with Bacteroides abundance. The increases in Bacteroides abundance were even greater in BCO2 KO mice, compared to the WT. Furthermore, Akkermansia abundance was significantly increased in BCO2 KO mice after IAV infection. Conclusions: Association of xanthophyll accumulation with the gut microbiota shift could protect animals from IAV infection by reducing local inflammation. Bacteroides potentially plays a beneficial role in this process.Item Zeaxanthin Drives Dynamic Changes in the Mouse Metabolome Through Gut Microbiome Shift(Elsevier, 2021) Lu, Peiran; Wong, Siau Yen; Chai, Jianmin; Jasbi, Paniz; Wu, Lei; Lyu, Yi; Tang, Minghua; Smith, Brenda; Lucas, Edralin; Clarke, Stephen L.; Chowanadisai, Winyoo; Shen, Xinchun; He, Hui; Zhao, Jiangchao; Gu, Haiwei; Conway, Tyrrell; Wyss, Adrian; Lin, Dingbo; Obstetrics and Gynecology, School of MedicineObjectives: Zeaxanthin, an oxygenized carotenoid, exerts antioxidant properties in human nutrition and metabolism. Like other carotenoids, zeaxanthin is poorly absorbed in the small intestine. The large portion of zeaxanthin reaches the colon and is not fully recovered in the colon. In this study, we aimed to investigate the association of zeaxanthin intake with the gut microbiome homeostasis and metabolomic responses in mice. Methods: Six-week-old male and female C57BL/6J wild type (WT), beta-carotene oxygenase 2 (BCO2) knockout mice were fed with AIN93M chow diets supplemented with or without zeaxanthin (0.02% w/w) for 10 weeks. At the termination of the study, mice were fasted for 3 hrs prior to euthanization. Cecal contents, colon, serum, feces, and other tissues were collected for laboratory assessments.16S rRNA sequencing and LC-MS/MS were performed for gut microbiota profiling and serum and fecal metabolomics analysis, respectively. Results: Significant zeaxanthin accumulation occurred in BCO2 KO, but not WT mice. Zeaxanthin accumulation was associated with the alteration of colonic gut microbiota composition, for example, zeaxanthin-increased abundance in Lachnospiraceae, Proteobacteria, and Parabacteroides, indicating enhanced short-chain production, improved intestinal integrity, and anaerobic bacterial colonization. The results of fecal and serum metabolomics revealed that zeaxanthin significantly altered tyrosine metabolism, branched-chain fatty acid oxidation, fatty acid biosynthesis, and phospholipid biosynthesis, and suppressed levels of kynurenine and trimethylamine N-oxide (TMAO). Conclusions: The results suggested that zeaxanthin accumulation promotes gut microbiome homeostasis and alters the gut microbial metabolites as signals in stimulating the host-gut microbe interplay.