Kequan Zhou’s research while affiliated with Wayne State University and other places

Background: More than half of the states in the U.S. report that over 30% of adults are obese. Obesity increases the risk of many chronic diseases, including type 2 diabetes, hypertension, and cardiovascular disease, and can even reduce one's lifespan. Similarly, the prevalence of type 2 diabetes follows a comparable trend. As a result, researchers are striving to find solutions to reduce obesity rates, with a particular focus on gut health, which has been previously linked to both obesity and type 2 diabetes. Recent studies suggest that Akkermansia muciniphila (Akk) may have a positive probiotic effect on preventing the onset of type 2 diabetes and obesity. Methods: We conducted a quantitative meta-analysis of 15 qualified animal studies investigating the effects of Akk administration as a probiotic. Results: The statistical analyses showed that Akk administration significantly reduced body weight gain by 10.4% and fasting blood glucose by 21.2%, while also significantly improving glucose tolerance by 22.1% and increasing blood insulin levels by 26.9%. However, our analysis revealed substantial heterogeneity between the control and experimental groups across all subgroups. Conclusions: Overall, Akk appears to be effective at reducing the onset of type 2 diabetes and diet-induced obesity. Long-term studies with larger sample sizes are needed to confirm these beneficial effects, as the current animal studies were of short duration (less than 20 weeks).

More than half of the states in the U.S. report that over 30% of adults are obese. Obesity increases the risk of many chronic diseases, including type 2 diabetes, hypertension, cardiovascular disease, and can even reduce one’s lifespan. Similarly, the prevalence of type 2 diabetes follows a comparable trend. As a result, researchers are striving to find solutions to reduce obesity rates, with a particular focus on gut health, which has been previously linked to both obesity and type 2 diabetes. Recent studies suggest that Akkermansia muciniphila(AKK) may have a positive probiotic effect on preventing the onset of type 2 diabetes and obesity. We conducted a quantitative meta-analysis of 15 qualified animal studies investigating the effects of AKK administration as a probiotic. The statistical analyses showed that AKK administration significantly reduced body weight gain by 10.4% and fasting blood glucose by 21.2%, while also significantly improving glucose tolerance by 22.1% and increasing blood insulin levels by 26.9%. However, our analysis revealed substantial heterogeneity between the control and experimental groups across all subgroups. Overall, AKK appears to be effective at reducing the onset of type 2 diabetes and diet-induced obesity. Long-term studies with larger sample sizes are needed to confirm these beneficial effects, as the current animal studies were of short duration (less than 20 weeks).

Purpose Probiotic species of butyrate producers have been investigated for the potential in preventing and treating obesity and overweight. However, Clostridium cochlearium has not been linked with any health benefits. We hypothesized that C. cochlearium could be a promising new probiotic with health benefits in improving body weight control and insulin sensitivity. Methods Productions of short-chain fatty acids (SCFAs) were characterized for C. cochlearium by NMR and GC–MS analyses. Probiotic effects of C. cochlearium were evaluated through diet-induced obese (DIO) C57BL/6 mice. The influence of C. cochlearium administration on gut SCFAs was measured using GC–MS. LC–MS-based untargeted metabolomic profiling and multivariate analysis were used to assess the serum metabolic alteration, identify biomarkers and pathways in response to the C. cochlearium administration. Results After 17 weeks of diet intervention, body weight gain of CC group (fed with a high-fat diet supplemented with C. cochlearium) showed a 21.86% reduction from the high-fat diet (HF) control group (P < 0.001), which was specifically reflected on the significantly lowered fat mass (CC vs HF, 17.19 g vs 22.86 g, P < 0.0001) and fat percentage (CC vs HF, 41.25% vs 47.10%, P < 0.0001), and increased lean percentage (CC vs HF, 46.63% vs 43.72%, P < 0.05). C. cochlearium administration significantly reduced fasting blood glucose from week 8 (P < 0.05 or 0.01), and eventually improved insulin sensitivity (HOMA-IR, CC vs HF, 63.77 vs 143.13, P < 0.05). Overall lowered levels of SCFAs were observed in the gut content of CC group. Metabolomic analysis enabled the identification of 53 discriminatory metabolites and 24 altered pathways between CC and HF groups. In particularly, most of the pathway-matched metabolites showed positive correlations with body weight, which included glutamate, phenylalanine, ornithine, PCs, LPCs, AcCas, proline, 5,6-dihydrouracil, pyroglutamic acid, and 1-pyrroline-4-hydroxy-2-carboxylate. Conclusions The beneficial effects of C. cochlearium could be related to its ability to restore certain obesity-driven biomarkers and pathways, especially downregulating pathways related to specific amino acids, PCs, LPCs and AcCas. Further research is warranted to investigate related metabolites and metabolic pathways. C. cochlearium may be developed as a promising new probiotic for the prevention or alleviation of obesity and diabetes in human.

Objectives: Species Lactobacillus acidophilus and butyrate producer Clostridium cochlearium have been shown to have potential antiobesity effects. The aim of this study was to show that the combination of C. cochlearium and L. acidophilus (CC-LA) has beneficial effects on body weight control and glucose homeostasis in high-fat diet-induced obese (DIO) mice. Methods: In this study, thirty-six 6-wk-old male C57BL/6 mice were randomly assigned to three groups of 12 mice each. The experimental group (CC-LA) was administered with CC-LA mixture and fed ad libitum with a high-fat diet. High-fat diet (HF) control and low-fat diet (LF) control groups were treated with the same dose of sterile water as the CC-LA group. Results: After 17 wk of dietary intervention, the CC-LA group showed 17% less body weight gain than the HF group did (P < 0.01). The CC-LA group also showed significantly reduced incremental area under the curve of oral glucose tolerance test and homeostatic model assessment for insulin resistance compared with the HF group. The results from 16S rRNA sequencing analysis of gut microbiota showed that the CC-LA administration led to overall increased α-diversity indices, and a significant microbial separation from the HF group. The ratio of Firmicutes to Bacteroidetes (F/B) was reduced from 3.30 in the HF group to 1.94 in the CC-LA group. The relative abundances of certain obesity-related taxa were also decreased by CC-LA administration. Conclusion: The present study provided evidence that the CC-LA combination reduced obesity and improved glucose metabolism in high-fat diet-treated DIO mice, potentially mediated by the modulation of gut microbiota.

An extract of noni (Morinda citrifolia) fruits has shown potent inhibitory activity on gut bacterial β-glucuronidase, which could help reduce irinotecan-induced diarrhea. In this study, four bacterial β-glucuronidase inhibitors were obtained following bioactive assay-guided isolation, including two sesquineolignans, (7S,8S,7'R,8'R)-isoamericanol B (1) and americanol B (2), and two dineolignans, moricitrins A (3) and B (4). Compounds 2-4 are new, and the absolute configuration of compound 1 was determined for the first time. Their chemical structures were elucidated through HRESIMS and NMR spectra, and their absolute configurations were established via the comparison of the experimental and calculated electronic circular dichroism spectra. These compounds showed potent inhibition against gut bacterial β-glucuronidase with IC50 values in the range 0.62-6.91 μM. The inhibition presented specificity for β-glucuronidase, as all the compounds showed no or weak effects on digestive enzymes such as α-amylase, α-glucosidase, and lipase, suggesting that their gastrointestinal side effects could be minimized. These specific inhibitors as naturally occurring dietary compounds may be developed as promising candidates to alleviate irinotecan-induced diarrhea.

In type 2 diabetes, the increase in the activity of the key enzymes that control glycogenolysis and gluconeogenesis in the liver causes an increase in hepatic glucose production, which is the main contributor to the development of fasting hyperglycemia. Here, we investigated the anti‐diabetic potential of flavonol kaempferol. Oral administration of kaempferol (50 mg/kg) significantly improved fasting blood glucose levels, glucose intolerance, and insulin sensitivity in high‐fat diet‐induced obese insulin resistant mice. These beneficial effects were associated with improved pyruvate tolerance and reduced hepatic glucose production. Consistently, kaempferol treatment increased Akt and hexokinase activity but decreased pyruvate carboxylase activity in the liver of obese mice. Kaempferol also enhanced whole body insulin sensitivity without altering body weight gain, food consumption, or adiposity of obese mice. These kaempferol actions were also demonstrated in STZ‐induced insulin‐deficient diabetic mice. In vitro, kaempferol increases glucose uptake of primary human skeletal muscle cells while reducing gluconeogenesis in HepG2 cells. These findings suggest that kaempferol may be a naturally occurring anti‐diabetic compound by improving insulin sensitivity and suppressing glucose production. Support or Funding Information The work was supported by grants from NCCIH of NIH (1R01AT007077, 1R01AT007566).

In diabetes mellitus, the excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can be used to ameliorate diabetes in an animal model of insulin deficiency and further explored the mechanism underlying the anti-diabetic effect of this flavonol. We demonstrate that oral administration of kaempferol (50 mg/kg/day) to streptozotocin-induced diabetic mice significantly improved hyperglycemia and reduced the incidence of overt diabetes from 100% to 77.8%. This outcome was accompanied by a reduction in hepatic glucose production and an increase in glucose oxidation in the muscle of the diabetic mice, whereas body weight, calorie intake, body composition, and plasma insulin and glucagon levels were not altered. Consistently, treatment with kaempferol restored hexokinase activity in the liver and skeletal muscle of diabetic mice while suppressed hepatic pyruvate carboxylase activity and gluconeogenesis. These results suggest that kaempferol may exert antidiabetic action via promoting glucose metabolism in skeletal muscle and inhibiting gluconeogenesis in the liver.

Urban agricultural soils can be an important reservoir of antibiotic resistance and have great food safety and public health indications. This study was to investigate antibiotic-resistant bacteria and antibiotic resistance genes in urban agricultural soils using phenotypic and metagenomic tools. A total of 207 soil bacteria were recovered from 41 soil samples collected from an urban agricultural garden in Detroit, USA. The most prevalent antibiotic resistance phenotypes demonstrated by Gram-negative bacteria was the resistance to ampicillin (94.2%), followed by chloramphenicol (80.0%), cefoxitin (79.5%), gentamicin (78.4%), and ceftriaxone (71.1%). Gram-positive bacteria were all resistant to gentamicin, kanamycin, and penicillin. Genes encoding resistance to quinolone, β-lactam, and tetracycline were the most prevalent and abundant in the soil. qepA and tetA, both encoding efflux pumps, predominated in quinolone and tetracycline resistance genes tested, respectively. Positive correlation (p < 0.05) was identified among groups of antibiotic resistance genes and between antibiotic resistance genes and metal resistance genes. The data demonstrated a diverse population of antibiotic resistance in urban agricultural soils. Phenotypic determination together with soil metagenomics proved to be a valuable tool to study the nature and extent of antibiotic resistance in the environment.

α‐Glucosidases have been a major target in controlling and managing postprandial blood glucose and therefore diabetes treatment. This study aims to further identify and purify active compounds from the most active ethyl acetate fraction collected previously in Tinta Cão grape pomace extract (TCEE) using a newly developed and highly effective immobilization method, including obtaining compounds previously shown to inhibit the enzyme. Purification used crosslinked chitosan beads with α‐glucosidases bound to polymer, which acted as immobilized enzyme vehicle to collect inhibitors. Compounds absorbed into the beads were eluded using methanol, where collected fraction was subjected to UHPLC‐MS analysis to identify active compounds. Results presented 5 major compounds: viniferifuran (amurensin H), p‐coumaroyl‐6‐O‐D‐glucopyranoside, p‐coumaroyl‐6‐O‐hexoside, (epi)catechin‐hexoside, 10‐carboxyl‐pyranopeonidin 3‐O‐(6′′‐O‐p‐coumaroyl)‐glucoside. These findings indicated the particular molecules can be utilized as potent α‐glucosidases inhibitors, and may be further tested for postprandial glucose control. Practical Application A potential approach enriched and identified α‐glucosidase inhibitors of grape pomace. Set‐up of UHPLC/MS detection and identification of active compounds provide qualify assessment in developing grape pomace extract into potent dietary supplement and new drug for diabetes.