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Effect of Long-Term and Short-Term Imbalanced Zn Manipulation on Gut Microbiota and Screening for Microbial Markers Sensitive to Zinc Status.

ABSTRACT: Zinc (Zn) imbalance is a common single-nutrient disorder worldwide, but little is known about the short-term and long-term effects of imbalanced dietary zinc in the intestinal microbiome. Here, 3-week-old C57BL/6 mice were fed diets supplemented with Zn at the doses of 0 (low Zn), 30 (control Zn), 150 (high Zn), and 600 mg/kg of body weight (excess Zn) for 4 weeks (short term) and 8 weeks (long term). The gut bacterial composition at the phyla, genus, and species levels were changed as the result of the imbalanced Zn diet (e.g., Lactobacillus reuteri and Akkermansia muciniphila). Moreover, pathways including carbohydrate, glycan, and nucleotide metabolism were decreased by a short-term low-Zn diet. Valeriate production was suppressed by a long-term low-Zn diet. Pathways such as drug resistance and infectious diseases were upregulated in high- and excess-Zn diets over 4-week and 8-week intervals. Long-term zinc fortification doses, especially at the high-Zn level, suppressed the abundance of short-chain fatty acids (SCFAs)-producing genera as well as the concentrations of metabolites. Finally, Melainabacteria (phylum) and Desulfovibrio sp. strain ABHU2SB (species) were identified to be potential markers for Zn status with high accuracy (area under the curve [AUC], >0.8). Collectively, this study identified significant changes in gut microbial composition and its metabolite concentration in altered Zn-fed mice and the relevant microbial markers for Zn status. IMPORTANCE Zn insufficiency is an essential health problem in developing countries. To prevent the occurrence of zinc deficit, zinc fortification and supplementation are widely used. However, in developed countries, the amounts of Zn consumed often exceed the tolerable upper intake limit. Our results demonstrated that dietary Zn is an essential mediator of microbial community structure and that both Zn deficiency and Zn overdose can generate a dysbiosis in the gut microbiota. Moreover, specific microbial biomarkers of Zn status were identified and correlated with serum Zn level. Our study found that a short-term low-Zn diet (0 mg/kg) and a long-term high-zinc diet (150 mg/kg) had obvious negative effects in a mouse model. Thus, these results indicate that the provision and duration of supplemental Zn should be approached with caution.

SUBMITTER: Chen L

PROVIDER: S-EPMC8567254 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveCompulsive behaviors are a core feature of obsessive-compulsive spectrum disorders but appear across a broad spectrum of psychological conditions. It is thought that compulsions reflect a failure to override habitual behaviors "stamped in" through repeated practice and short-term distress reduction. Animal models suggest a possible causal role of the orbitofrontal cortex (OFC) in compulsive behaviors, but human studies have largely been limited by correlational designs. The goal of this study was to establish the first experimental evidence in humans for a mechanistic model in order to inform further experimental work and the eventual development of novel mechanistic treatments involving synergistic biological-behavioral pairings.MethodsAfter a baseline assessment, 69 individuals with compulsive behavior disorders were randomly assigned, in a double-blind, between-subjects design, to receive a single session of one of two active stimulation conditions targeting the left OFC: intermittent theta burst stimulation (iTBS), expected to increase OFC activity, or continuous TBS (cTBS), expected to decrease activity (both conditions, 600 pulses at 110% of target resting motor threshold). In both conditions, brain modulation was paired with a subsequent computer task providing practice in overriding a clinically relevant habit (an overlearned shock avoidance behavior), delivered during the expected window of OFC increase or decrease. Pre- and post-TBS functional MRI assessments were conducted of target engagement and compulsive behaviors performed in response to an idiographically designed stressful laboratory probe.ResultscTBS and iTBS modulated OFC activation in the expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of compulsive behaviors 90 minutes after TBS. These acute behavioral effects persisted 1 week after cTBS.ConclusionsExperimental modulation of the OFC, within the behavioral context of habit override training, affected short-term markers of compulsive behavior vulnerability. The findings help delineate a causal translational model, serving as an initial precursor to mechanistic intervention development.

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Effect of Long-Term and Short-Term Imbalanced Zn Manipulation on Gut Microbiota and Screening for Microbial Markers Sensitive to Zinc Status.

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