Aside from the COVID-19 pandemic, the obesity and diabetes pandemics have threatened global health. Patients with diabetes are more likely to experience serious complications from COVID-19; thus, preventing obesity-associated diabetes is of paramount important. Furthermore, the development of a method to prevent diabetes and elucidation of its pathology is a currently urgent issue. We previously reported that thiamine plays a key role in suppressing abnormal glycolipid metabolism in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of obesity-associated diabetes. However, whether thiamine affects only OLETF rats or other animal models including a type 2 diabetes model with a different pathology requires elucidation. In this study, leptin-receptor deficiency mice were used as a model of type 2 diabetes with a different pathology to evaluate the efficacy of thiamine. The mice had free access to water containing 0.2% thiamine for 9 weeks, and the results showed that food and water consumption decreased in db/db-homo mice. Urine output, body weight gains and blood glucose levels decreased in mice that received thiamine. There were 5 mice and 1 mouse with a fasting glucose level of ≥ 300 mg/dL in the db/db-homo control group (n = 10) and db/db-homo thiamine group (n = 10), respectively, suggesting that thiamine intake may suppress an increase in blood glucose levels. The results of the present study suggest that demand for thiamine may exceed the normal range in in vivo mouse models of diabetes and continuous thiamine intake affects diabetes onset and progression.

2-Butylbenzo[d]isothiazol-3(2H)-one (BBIT, CAS No. 4299-07-4) is widely used as an industrial antiseptic and antifungal agent. To investigate its toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral toxicological study of BBIT was conducted in Crl:CD (SD) rats at doses of 0 (vehicle control, corn oil), 30, 90, or 270 mg/kg/day. There was no mortality or abnormal clinical signs related to treatment in any group. Slightly decreased body weight and food consumption were observed in the 270 mg/kg group in females. Increased urine volume and kidney weight, increased liver weight, and thickening of the forestomach mucosa in autopsy were observed in both sexes in the 270 mg/kg group. Histopathological examination revealed that hyperplasia of the squamous epithelium of the forestomach with parakeratosis and/or hyperkeratosis was observed in both sexes in all the BBIT-treated groups. Moreover, centrilobular hypertrophy of hepatocytes was observed in both sexes of the 270 mg/kg group. Similarly, increased depositions of eosinophilic bodies and/or hyaline droplets in the proximal tubules of the kidney were observed among the male in the 270 mg/kg group. Based on the forestomach changes, NOAEL was judged to be less than 30 mg/kg/day in both sexes under this study’s conditions.

2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methylphenol (BTMLP, CAS No. 125304-04-3) is widely used as a liquid ultraviolet absorber that prevents deterioration of synthetic resins and so on. To investigate its toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral toxicological study of BTMLP was conducted in Crl:CD (SD) rats at doses of 0 (vehicle control, corn oil), 100, 300, and 1000 mg/kg/day. There was no observed mortality or abnormal clinical signs related to the treatment of any group. Body weight and food consumption were not affected by BTMLP treatment. In males, significant prolongations of prothrombin time and activated partial thrombin time were observed in the BTMLP-treated groups. Histopathological examination revealed a slight increase of the eosinophilic bodies and hyaline droplets in the renal cortical tubules in the 1000 mg/kg group in males. As mentioned above, the toxic effect of the BTMLP was noted in the blood coagulation system and kidneys only in males. Based on these findings, the NOAEL was judged to be less than 100 mg/kg/day in males and 1000 mg/kg/day in females under this study’s condition.

To investigate the effects of Chlorella alga on gut microbiota dysbiosis in type-2 diabetes (T2D). The stress perception of patients was also investigated. Chlorella (3 g/day) was administered to patients with T2D (n = 10) for a period of 30 days. Gut microbiota composition was analysed by 16S rDNA gene sequencing, and stress perception was evaluated using the perceived stress scale (PSS). A total of 13 phyla, 89 families, and 185 genera were identified from all faecal samples of patients with T2D, and Firmicutes and Bacteroidetes were the most dominant phyla among all samples. Chlorella decreased Bacteroidetes and increased Firmicutes. The proportions of the Akkermansia, Coprococcus, Dorea, Lachnospira, Phascolarctobacterium, and Ruminococcus generas increased, whereas the proportion of Paraprevotella, Prevotella, Klebsiella, and Sutterella decreased in the faeces of patients with T2D after Chlorella intake. Chlorella induced a significant reduction in perceived stress in patients with T2D, and better PSS scores negatively correlated with an increase in Akkermansia, Coprococcus, Dorea, Lachnospira, Phascolarctobacterium, and Ruminococcus and positively correlated with a decrease in Paraprevotella, Prevotella, Klebsiella, and Sutterella. Altogether, these results show the ability of Chlorella to positively modulate gut dysbiosis, leading to reduced stress perception in patients with T2D. Our findings contribute to the globally increasing search for new preventive and therapeutic strategies aimed at restoring the balance of the intestinal ecosystem.

The long-term effects of Chlorella doses on the inflammatory status and quality of life (QoL) of individuals with type-2 diabetes (T2D), and prediabetes (pre-T2D), and of nondiabetic controls were investigated. Chlorella was administered for 12 months; 1.6 g/day for the first six months and 3 g/day for the following six months. The inflammatory profile was studied by quantification of cytokines, adipokines and incretins. QoL was evaluated using the Short Form-36 health survey questionnaire (SF-36). Evaluations were performed at baseline, 6 (T6) and 12 (T12) months after initiating Chlorella intake. At baseline, QoL was more deeply impacted in T2D, a similar proinflammatory profile was observed in T2D and pre-T2D. In both, at T6 and T12, Chlorella modulated the altered levels of adipocytokines and incretins towards healthy values, and significantly improved QoL. Moderate correlations between the modulation by the alga and enhancement in QoL were observed only in the T2D group. In the nondiabetic control group, Chlorella improved QoL vitality and mental health scores. No differences were found between the two doses. Our results illustrate Chlorella adaptogen activity on inflammatory pathways and suggest its promising use as a complementary alternative in treating diseases related to insulin resistance in a wide range of chronic low-grade systemic inflammation-related diseases. Moreover, Chlorella increased QoL in all groups, the ultimate goal of all healthy interventions. Altogether, our findings suggest that one core mechanism involved in the homeostatic response produced by Chlorella is related to its rich content of carotenoids, operating mainly through inhibition of the NF-κB signalling pathway.