Gut Microbes Are Associated with the Vascular Beneficial Effects of Dietary Strawberry on Metabolic Syndrome‐Induced Vascular Inflammation

Miller, James Coleman; Babu, Adhini Kuppuswamy Satheesh; Petersen, Chrissa; Wankhade, Umesh D.; Robeson, Michael S.; Putich, Madison; Mueller, Jaime A.; O'Farrell, Aubrey Sarah; Cho, Jae Min; Chintapalli, Sree V.; Jalili, Thunder; Symons, J. David; Babu, Pon Velayutham Anandh

doi:10.1002/mnfr.202200112

Cited by 9 publications

(17 citation statements)

References 59 publications

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“…Evidence indicates a strong link between diet, gut microbes, and cardiovascular health. 9,37 Indeed, the effect of diet-derived microbial metabolites such as short-chain fatty acids and TMAO on vasculature is well-documented. 1,9 Human studies showed that circulating TMAO and its precursors are associated with an increased risk of cardiovascular disease, atherosclerotic burden, and death due to arterial diseases.…”

Section: Discussionmentioning

confidence: 99%

Blueberry intervention mitigates detrimental microbial metabolite trimethylamine N‐oxide by modulating gut microbes

Satheesh Babu,

Petersen,

Iglesias‐Carres

et al. 2023

BioFactors

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Gut microbes play a pivotal role in host physiology by producing beneficial or detrimental metabolites. Gut bacteria metabolize dietary choline and L‐carnitine to trimethylamine (TMA) which is then converted to trimethylamine‐N‐oxide (TMAO). An elevated circulating TMAO is associated with diabetes, obesity, cardiovascular disease, and cancer in humans. In the present study, we investigated the effect of dietary blueberries and strawberries at a nutritional dosage on TMA/TMAO production and the possible role of gut microbes. Blueberry cohort mice received a control (C) or freeze‐dried blueberry supplemented (CB) diet for 12 weeks and subgroups received an antibiotics cocktail (CA and CBA). Strawberry cohort mice received a control (N) or strawberry‐supplemented (NS) diet and subgroups received antibiotics (NA and NSA). Metabolic parameters, choline, TMA, and TMAO were assessed in addition to microbial profiling and characterization of berry powders. Blueberry supplementation (equivalent to 1.5 human servings) reduced circulating TMAO in CB versus C mice (~48%) without changing choline or TMA. This effect was not mediated through alterations in metabolic parameters. Dietary strawberries did not reduce choline, TMA, or TMAO. Depleting gut microbes with antibiotics in these cohorts drastically reduced TMA and TMAO to not‐quantified levels. Further, dietary blueberries increased the abundance of bacterial taxa that are negatively associated with circulating TMA/TMAO suggesting the role of gut microbes. Our phenolic profiling indicates that this effect could be due to chlorogenic acid and increased phenolic contents in blueberries. Our study provides evidence for considering dietary blueberries to reduce TMAO and prevent TMAO‐induced complications.

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Section: Discussionmentioning

confidence: 99%

Blueberry intervention mitigates detrimental microbial metabolite trimethylamine N‐oxide by modulating gut microbes

Satheesh Babu,

Petersen,

Iglesias‐Carres

et al. 2023

BioFactors

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“…Blood glucose concentrations were measured at 0, 15, 30, 60, and 120 min following glucose administration. [39,40] An intraperitoneal insulin tolerance test (IPITT) was conducted after a 4-h fast following insulin injection (0.75 units kg −1 of body weight). Blood glucose concentrations were measured 0, 15, 30, 60, and 120 min after insulin injection.…”

Section: Methodsmentioning

confidence: 99%

“…Blood glucose concentrations were measured 0, 15, 30, 60, and 120 min after insulin injection. [39,40] Using the LF50 body composition mice analyzer (Minispec; Bruker, Germany), total body fat and lean body mass was assessed by TD-NMR. [39,40] After the 12-week treatment period, mice were anesthetized with 2%-5% isoflurane.…”

Section: Methodsmentioning

confidence: 99%

“…[39,40] Using the LF50 body composition mice analyzer (Minispec; Bruker, Germany), total body fat and lean body mass was assessed by TD-NMR. [39,40] After the 12-week treatment period, mice were anesthetized with 2%-5% isoflurane. The cecum and other organs were collected immediately after the euthanasia of the animals.…”

Section: Methodsmentioning

confidence: 99%

“…Validation of Microbial Depletion by 16s rRNA Amplicon Sequencing: In addition to culture-based methods, the depletion of gut microbes in antibiotic-treated mice was assessed by the 16s rRNA amplification method, as previously described. [40] Bacterial genomic DNA was extracted from the cecal contents of the experimental mice using the DNeasy Pow-erSoil Kit (Qiagen, USA). A quantity of 50 ng of genomic DNA was used to amplify the V4 variable region of the 16S rRNA gene employing the 515F/806R primers.…”

Section: Methodsmentioning

confidence: 99%

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Gut Microbiota Depletion Using Antibiotics to Investigate Diet‐Derived Microbial Metabolites: An Efficient Strategy

Satheesh Babu,

Petersen,

Paz

et al. 2023

Molecular Nutrition Food Res

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ScopeGut microbiota depletion using antibiotics in drinking water is a valuable tool to investigate the role of gut microbes and microbial metabolites in health and disease. However, there are challenges associated with this model. Animals avoid drinking water because of the antibiotic bitterness, which affects their metabolic health. The present study develops an efficient strategy to deplete gut microbes without affecting metabolic parameters.Methods and resultsMale C57BL/6J mice (7 weeks old) are fed a control (C) or high‐fat (HF) diet. Subgroups of C and HF mice receive an antibiotic cocktail in drinking water (CA and HA). The antibiotic dosage is gradually increased so that the animals adapt to the taste of antibiotics. Metabolic parameters, gut microbiome, and microbial metabolites are assessed after 12 weeks treatment. Culture methods and 16s rRNA amplification confirm the depletion of gut microbes in antibiotic groups (CA and HA). Further, antibiotic treatment does not alter metabolic parameters (body weight, body fat, lean body mass, blood glucose, and glucose/insulin tolerance), whereas it suppresses the production of diet‐derived microbial metabolites (trimethylamine and trimethylamine‐N‐oxide).ConclusionThis strategy effectively depletes gut microbes and suppresses the production of microbial metabolites in mice without affecting their metabolic health.

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Diet-Induced Rodent Obesity Is Prevented and the Fecal Microbiome Is Improved with Elderberry (Sambucus nigra ssp. canadensis) Juice Powder

Minj,

Riordan,

Teets

et al. 2024

J. Agric. Food Chem.

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Anthocyanin-rich edible berries protect against diet-induced obesity in animal models. Prevention is mediated through the bidirectional relationship with the fecal microbiome, and gut-derived phenolic metabolite absorption increases with physical activity, which may influence bioactivity. The objective of this study was to test elderberry juice powder on the development of diet-induced obesity and its influence on the fecal microbiome alone or in combination with physical activity. Male C57BL/6J mice were assigned to one of four treatments, including (1) high-fat diet without wheel access; (2) high-fat diet with unlimited wheel access; (3) high-fat diet supplemented with 10% elderberry juice powder without wheel access; and (4) high-fat diet supplemented with 10% elderberry juice powder with unlimited wheel access. Body weight gain, fat pads, and whole-body fat content in mice fed elderberry juice were significantly less than in mice fed the control diet independent of wheel access. At the end of the study, active mice fed elderberry juice ate significantly more than active mice fed a control diet. There was no difference in the physical activity between active groups. Elderberry juice increasedBifidobacterium, promotedAkkermansia and Anaeroplasma, and prevented the growth of Desulfovibrio. Elderberry juice is a potent inhibitor of diet-induced obesity with action mediated by the gut microbiota.

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Gut Microbes Are Associated with the Vascular Beneficial Effects of Dietary Strawberry on Metabolic Syndrome‐Induced Vascular Inflammation

Cited by 9 publications

References 59 publications

Blueberry intervention mitigates detrimental microbial metabolite trimethylamine N‐oxide by modulating gut microbes

Blueberry intervention mitigates detrimental microbial metabolite trimethylamine N‐oxide by modulating gut microbes

Gut Microbiota Depletion Using Antibiotics to Investigate Diet‐Derived Microbial Metabolites: An Efficient Strategy

Diet-Induced Rodent Obesity Is Prevented and the Fecal Microbiome Is Improved with Elderberry (Sambucus nigra ssp. canadensis) Juice Powder

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