The programming effects of nutrition‐induced catch‐up growth on gut microbiota and metabolic diseases in adult mice

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

Download Full-text

The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, l-carnitine and related precursors by the human gut microbiota

European Journal of Nutrition ◽

10.1007/s00394-021-02572-6 ◽

2021 ◽

Author(s):

Priscilla Day-Walsh ◽

Emad Shehata ◽

Shikha Saha ◽

George M. Savva ◽

Barbora Nemeckova ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Human Colon ◽

Human Studies ◽

Bacterial Strains ◽

Increased Risk ◽

Carnitine Metabolism ◽

Registration Number ◽

Vitro Model

Abstract Purpose Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. Methods TMA production from choline, l-carnitine, betaine and γ-butyrobetaine was studied over 24–48 h using an in-vitro human colon model with metabolite quantification performed using LC–MS. Results Choline was metabolised via the direct choline TMA-lyase route but not the indirect choline–betaine-TMA route, conversion of l-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for l-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA. Conclusion The metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. Trial registration number NCT02653001 (http://www.clinicaltrials.gov), registered 12 Jan 2016.

Download Full-text

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽

10.3390/metabo11080499 ◽

2021 ◽

Vol 11 (8) ◽

pp. 499

Author(s):

Kalpana D. Acharya ◽

Hye L. Noh ◽

Madeline E. Graham ◽

Sujin Suk ◽

Randall H. Friedline ◽

...

Keyword(s):

Gut Microbiota ◽

Energy Homeostasis ◽

Whole Body ◽

Glucose Turnover ◽

Female Mice ◽

Adult Mice ◽

Diet Induced Obesity ◽

Metabolic Dysregulation ◽

Regulation Of Metabolism ◽

Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

Download Full-text

The Relationship between Frequently Used Glucose-Lowering Agents and Gut Microbiota in Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2018/1890978 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

You Lv ◽

Xue Zhao ◽

Weiying Guo ◽

Ying Gao ◽

Shuo Yang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Short Chain Fatty Acids ◽

Current Evidence ◽

Diabetic Patients ◽

Glucose Lowering ◽

Patients With Diabetes ◽

Gastrointestinal Side Effects ◽

Underlying Mechanisms

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.

Download Full-text

Impacts of early-life paraquat exposure on gut microbiota and body weight in adult mice

Chemosphere ◽

10.1016/j.chemosphere.2021.133135 ◽

2021 ◽

pp. 133135

Author(s):

Yixi Li ◽

Zhenzi Zuo ◽

Bing Zhang ◽

Huan Luo ◽

Bo Song ◽

...

Keyword(s):

Body Weight ◽

Gut Microbiota ◽

Early Life ◽

Adult Mice

Download Full-text

Nuciferine improves high-fat diet-induced obesity by reducing intestinal permeability through increasing autophagy and remodeling the gut microbiota

Food & Function ◽

10.1039/d1fo00367d ◽

2021 ◽

Author(s):

Zhen Shi ◽

Zhiyuan Fang ◽

Xinxing Gao ◽

Hao Yu ◽

Yiwei Zhu ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Permeability ◽

High Fat Diet ◽

Metabolic Diseases ◽

High Fat ◽

Diet Induced Obesity ◽

Medicinal Value

Nuciferine (NF) has received extensive attention for its medicinal value in the treatment of metabolic diseases, such as obesity, but the effects of NF on obesity-related intestinal permeability, autophagy and...

Download Full-text

Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism

Science Advances ◽

10.1126/sciadv.aax6208 ◽

2020 ◽

Vol 6 (1) ◽

pp. eaax6208 ◽

Cited By ~ 16

Author(s):

Su-Ling Zeng ◽

Shang-Zhen Li ◽

Ping-Ting Xiao ◽

Yuan-Yuan Cai ◽

Chu Chu ◽

...

Keyword(s):

Metabolic Syndrome ◽

Amino Acid ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Amplicon Sequencing ◽

Therapeutic Interventions ◽

Protective Effects ◽

Fecal Microbiome ◽

Metabolomic Profiling ◽

Branched Chain

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)–induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.

Download Full-text

Integrity of the Intestinal Barrier: The Involvement of Epithelial Cells and Microbiota—A Mutual Relationship

Animals ◽

10.3390/ani12020145 ◽

2022 ◽

Vol 12 (2) ◽

pp. 145

Author(s):

Małgorzata Gieryńska ◽

Lidia Szulc-Dąbrowska ◽

Justyna Struzik ◽

Matylda Barbara Mielcarska ◽

Karolina Paulina Gregorczyk-Zboroch

Keyword(s):

Epithelial Cells ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Intercellular Junctions ◽

Gi Tract ◽

First Line ◽

Mucosal Integrity ◽

Physical Defense ◽

Mutualistic Relationship

The gastrointestinal tract, which is constantly exposed to a multitude of stimuli, is considered responsible for maintaining the homeostasis of the host. It is inhabited by billions of microorganisms, the gut microbiota, which form a mutualistic relationship with the host. Although the microbiota is generally recognized as beneficial, at the same time, together with pathogens, they are a permanent threat to the host. Various populations of epithelial cells provide the first line of chemical and physical defense against external factors acting as the interface between luminal microorganisms and immunocompetent cells in lamina propria. In this review, we focus on some essential, innate mechanisms protecting mucosal integrity, thus responsible for maintaining intestine homeostasis. The characteristics of decisive cell populations involved in maintaining the barrier arrangement, based on mucus secretion, formation of intercellular junctions as well as production of antimicrobial peptides, responsible for shaping the gut microbiota, are presented. We emphasize the importance of cross-talk between gut microbiota and epithelial cells as a factor vital for the maintenance of the homeostasis of the GI tract. Finally, we discuss how the imbalance of these regulations leads to the compromised barrier integrity and dysbiosis considered to contribute to inflammatory disorders and metabolic diseases.

Download Full-text

Bacterial Taxa Associated with High Adherence to Mediterranean Diet in a Spanish Population

Proceedings ◽

10.3390/iecn2020-07001 ◽

2020 ◽

Vol 61 (1) ◽

pp. 10

Author(s):

Carles Rosés ◽

Amanda Cuevas-Sierra ◽

Salvador Quintana ◽

José I. Riezu-Boj ◽

J. Alfredo Martínez ◽

...

Keyword(s):

Gut Microbiota ◽

Dietary Intake ◽

Mediterranean Diet ◽

Dietary Habits ◽

Metabolic Diseases ◽

Positive Association ◽

Normal Weight ◽

Statistical Tool ◽

High Adherence ◽

Health And Disease

The Mediterranean diet (MD) is recognised as one of the healthiest diets worldwide and is associated with the prevention of cardiovascular and metabolic diseases, among others. Dietary habits are considered one of the strongest modulators of the gut microbiota, which seems to play a significant role in the health and disease of the host. The purpose of the present study was to evaluate interactive associations between gut microbiota composition and habitual dietary intake in 360 Spanish adults of the Obekit cohort (normal weight, overweight and obese subjects). Dietary intake and adherence to the MD tests together with faecal samples were collected from each subject. Faecal 16S rRNA sequencing was performed and checked against the dietary habits. MetagenomeSeq was the statistical tool applied to analyse at the species taxonomic level. Results from this study confirm that a strong adherence to the MD increases the population of some beneficial bacteria, improving microbiota status towards a healthier pattern. Bifidobacterium animalis is the species with the strongest association with the MD. One of the highlights is the positive association between several SCFA-producing bacteria and high adherence to the MD. In conclusion, this study shows that MD, fibre, legumes, vegetables, fruit and nuts intakes are associated with an increase in butyrate-producing taxa such as Roseburia faecis, Ruminococcus bromii and Oscillospira (Flavonifractor) plautii.

Download Full-text

The effects of gut microbiota on metabolic outcomes in pregnant women and their offspring

Food & Function ◽

10.1039/c8fo00601f ◽

2018 ◽

Vol 9 (9) ◽

pp. 4537-4547 ◽

Cited By ~ 4

Author(s):

You Lv ◽

Zi Yan ◽

Xue Zhao ◽

Xiaokun Gang ◽

Guangyu He ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gut Microbiota ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Metabolic Diseases ◽

Health Issues ◽

Metabolic Outcomes

Metabolic diseases such as gestational diabetes mellitus and obesity during pregnancy have become severe health issues due to adverse pregnant outcomes in recent years.

Download Full-text