Estimating population-level of alcohol, tobacco and morphine use in a small Russian region using wastewater-based epidemiology.

INTRODUCTION: Alcohol, tobacco and illicit drug use combined are the largest modifiable health risk factors. Wastewater-based epidemiology (WBE) is a complementary approach for monitoring substance use in the population. In this study we applied WBE technique to a community in the Moscow region to estimate population-level consumption of alcohol, tobacco and morphine. METHODS: Wastewater sampling was carried out over 47 days, in 2018 and 2019, including the New Year period. Analysis of the samples for consumption biomarkers (ethyl sulphate, cotinine and morphine) were undertaken using liquid chromatography tandem mass spectrometry (LC-MS/MS). Daily consumption estimates were then compared with sales/production/prescription data and between different days of the week using Mann-Whitney U test. RESULTS: Alcohol consumption was significantly higher on Sundays and during the New Year and Russian Christmas period compared to weekdays and Saturdays. Tobacco consumption estimates were largely consistent throughout the week. Morphine was detected by WBE during the monitoring period but was inconsistent with prescription record data. DISCUSSION AND CONCLUSIONS: This study provides evidence for the feasibility of conducting WBE in Russia. Estimates of alcohol consumption derived from WBE were higher than average alcohol sales data for the country. The estimated consumption of nicotine is generally consistent with the production data, with estimates higher than in most other countries. Our results also suggest potential illegal use of opioids (morphine-based) in the population. Given the considerable health and economic costs of substance use in Russia, more extensive WBE testing is recommended to inform and evaluate public health policies.

Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice.

The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1-5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.

Lactobacillus fermentum promotes adipose tissue oxidative phosphorylation to protect against diet-induced obesity.

The gut microbiota has pivotal roles in metabolic homeostasis and modulation of the intestinal environment. Notably, the administration of Lactobacillus spp. ameliorates diet-induced obesity in humans and mice. However, the mechanisms through which Lactobacillus spp. control host metabolic homeostasis remain unclear. Accordingly, in this study, we evaluated the physiological roles of Lactobacillus fermentum in controlling metabolic homeostasis in diet-induced obesity. Our results demonstrated that L. fermentum-potentiated oxidative phosphorylation in adipose tissue, resulting in increased energy expenditure to protect against diet-induced obesity. Indeed, oral administration of L. fermentum LM1016 markedly ameliorated glucose clearance and fatty liver in high-fat diet-fed mice. Moreover, administration of L. fermentum LM1016 markedly decreased inflammation and increased oxidative phosphorylation in gonadal white adipose tissue, as demonstrated by transcriptome analysis. Finally, metabolome analysis showed that metabolites derived from L. fermentum LM1016-attenuated adipocyte differentiation and inflammation in 3T3-L1 preadipocytes. These pronounced metabolic improvements suggested that the application of L. fermentum LM1016 could have clinical applications for the treatment of metabolic syndromes, such as diet-induced obesity.