Biology subjects

Chadaideh, K. S.

Publications and source records attributed to Chadaideh, K. S..

4 recordsLinked to original sources

bioRxiv2024

Dietary preservatives alter the gut microbiota in vitro and in vivo with sex-specific consequences for host metabolic development

Antibiotics in early life can promote adiposity via interactions with the gut microbiota. However, antibiotics represent only one possible route of antimicrobial exposure. Dietary preservatives exhibit antimicrobial activity, contain chemical structures accessible to microbial enzymes, and alter environmental conditions favoring specific microbial taxa. Therefore, preservatives that retain bioactivity in the gut might likewise alter the gut microbiota and host metabolism. Here we conduct in vitro, ex vivo, and in vivo experiments in mice to test the effects of preservatives on the gut microbiota and host physiology. We screened common dietary preservatives against a panel of human gut isolates and whole fecal communities, finding that preservatives strongly altered microbial growth and community structure. We exposed mice to diet-relevant doses of 4 preservatives [acetic acid, BHA (butylated hydroxyanisole), EDTA (ethylenediaminetetraacetic acid) and sodium sulfite], which each induced compound-specific changes in gut microbiota composition. Finally, we compared the long-term effects of early-life EDTA and low-dose antibiotic (ampicillin) exposure. EDTA exposure modestly reduced nutrient absorption and cecal acetate in both sexes, resulting in lower adiposity in females despite greater food intake. Females exposed to ampicillin also exhibited lower adiposity, along with larger brains and smaller livers. By contrast, in males, ampicillin exposure generally increased energy harvest and decreased energy expenditure, resulting in higher adiposity. Our results highlight the potential for everyday doses of common dietary preservatives to affect the gut microbiota and impact metabolism differently in males and females. Thus, despite their generally-regarded-as-safe designation, preservatives could have unintended consequences for consumer health. SIGNIFICANCEEarly-life exposure to antibiotics can alter the gut microbiota and shape adult metabolic health. Here we show that dietary preservatives can have analogous effects. Common dietary preservatives altered gut microbiota composition in vitro, ex vivo and in vivo. Early-life EDTA exposure had long-term, sex-specific consequences for energy metabolism. Simultaneously, we deliver new mechanistic understanding of early-life antimicrobial-induced effects on adiposity via evidence that low-dose ampicillin treatment increases energy harvest while conserving energy expenditure in males, promoting adiposity, while EDTA treatment dampens energy harvest, promoting leanness in females. Overall, our results emphasize that early-life gut microbiome disruptions can be triggered by diverse antimicrobial exposures, with previously unappreciated metabolic consequences that differ for males and females.

physiology↗

bioRxiv2021

Common proanthocyanidin-rich foods modulate gastrointestinal blooms of Akkermansia muciniphila in a diet-dependent manner

Developing methods to modulate growth of the mucin-degrading gut bacterium Akkermansia muciniphila could benefit patients with different health needs, as A. muciniphila has been associated with both positive metabolic health outcomes and detrimental neurodegenerative outcomes. Growth of A. muciniphila is sensitive to plant-derived polyphenols, and particularly proanthocyanidins (PACs), when administered in isolated form at supraphysiological doses. However, it remains unclear whether doses sufficient for these effects are achievable via diet. Here, we explore the extent to which nutritionally relevant doses of common polyphenol-rich foods - berries, wine, and coffee - influence A. muciniphila abundance in C57BL/6J mice under varying dietary conditions. By administering polyphenol-rich whole foods, comparing polyphenol-depleted and PAC-rich versus PAC-poor food supplements, and through gradient PAC-dosing experiments, we show that PAC-rich foods uniquely induce A. muciniphila growth at doses that are feasibly achieved through routine diet. Notably, the effects of PAC supplementation were detected against a high-fat diet but not a low-fat control diet background, highlighting the importance of habitual diet strategies in either amplifying or mitigating the prebiotic effects of PAC-rich food consumption. Ultimately, our work suggests that both PACs and diet influence A. muciniphila abundance with downstream impacts for human health.

microbiology↗

bioRxiv2021

Gut Microbiota predicts Healthy Late-life Aging in Male Mice

Calorie restriction (CR) extends lifespan and retards age-related chronic diseases in most species. There is growing evidence that the gut microbiota has a pivotal role in host health and age-related pathological conditions. Yet, it is still unclear how CR and the gut microbiota are related to healthy aging. Here we report findings from a small longitudinal study of male C57BL/6 mice maintained on either ad libitum or mild (15%) CR diets from 21 months of age and tracked until natural death. We demonstrate that CR results in a significant reduction in frailty index (FI), a well-established indicator of aging. We observed significant alterations in bacterial load, diversity, and compositional patterns of the mouse gut microbiota during the aging process. Interrogating the FI-related microbial features using machine learning techniques, we show that gut microbial signatures from 21-month-old mice can predict the healthy aging of 30-month-old mice with reasonable accuracy. This study deepens our understanding of the links between CR, gut microbiota, and frailty in the aging process of mice.

microbiology↗

bioRxiv2019

Parallel signatures of mammalian domestication and human industrialization in the gut microbiota

Domestication may have had convergent effects on the microbiota of domesticates and humans through analogous ecological shifts. Comparing the gut microbiota of domestic and related wild mammals plus humans and chimpanzees, we found consistent shifts in composition in domestic animals and in humans from industrialized but not traditional societies. Reciprocal diet switches in mice and canids demonstrated that diet played a dominant role in shaping the domestic gut microbiota, with stronger responses in the member of the wild-domestic pair with higher dietary and microbial diversity. Laboratory mice recovered wild-like microbial diversity and responsiveness with experimental colonization. We conclude that domestication and industrialization have similarly impacted the gut microbiota, emphasizing the utility of domestic animal models and diets for understanding host-microbial interactions in rapidly changing environments.

microbiology↗