Clostridium butyricum Strain CCFM1299 Reduces Obesity via Increasing Energy Expenditure and Modulating Host Bile Acid Metabolism.

Clostridium butyricum is a butyrate-producing microorganism which has beneficial effects on various diseases, including obesity. In our previous study, the anti-obesity Clostridium butyricum strain CCFM1299 (C20_1_1) was selected, but its anti-obesity mechanism was not clarified. Herein, CCFM1299 was orally administrated to high-fat-diet-treated C57BL/6J mice for 12 weeks to uncover the way the strain alleviates obesity. The results indicated that CCFM1299 alleviated obesity through increasing the energy expenditure and increasing the expression of genes related to thermogenesis in brown adipose tissue (BAT). Moreover, strain CCFM1299 could also affect the expression of immune-related genes in epididymal white adipose tissue (eWAT). This immunomodulatory effect might be achieved through its influence on the complement system, as the expression of the complement factor D (CFD) gene decreased significantly. From the view of metabolites, CCFM1299 administration increased the levels of ursodeoxycholic acid (UDCA) in feces and taurohyodeoxycholic acid (THDCA) in serum. Together, the anti-obesity potential of CCFM1299 might be attributed to the increase in energy consumption, the regulation of immune-related gene expression in eWAT, and the alteration of bile acid metabolism in the host. These provided new insights into the potential application of anti-obesity microbial preparations and postbiotics.

Clostridium butyricum Reduces Obesity in a Butyrate-Independent Way.

Accumulating evidence from recent studies links the gut microbiota to obesity, and microbiome therapy has been examined as a treatment. Clostridium butyricum (C. butyricum), an intestinal symbiont, protects the host from a range of diseases. Studies have shown a negative correlation between the relative abundance of C. butyricum and a predisposition for obesity. However, the physiological function and material basis of C. butyricum for obesity are unclear. Here, five C. butyricum isolates were administered to mice on a high-fat diet (HFD) to determine their anti-obesity effects. All isolates suppressed the formation and inflammation of subcutaneous fat, and the two effective strains considerably reduced weight gain and ameliorated dyslipidemia, hepatic steatosis, and inflammation. These positive effects were not achieved by increasing the concentration of intestinal butyrate, and the effective strains could not be replaced by sodium butyrate (NaB). We also discovered that oral supplementation with the two most effective strains changed the metabolism of tryptophan and purine and altered the composition of the gut microbiota. In summary, C. butyricum improved the metabolic phenotypes under the HFD by controlling the composition of the gut microbiota and modulating intestinal metabolites, thereby demonstrating its ability to fight obesity and providing a theoretical foundation for microbial preparations production.

Machine learning framework for gut microbiome biomarkers discovery and modulation analysis in large-scale obese population.

BACKGROUND: The gut microbiome has proven to be an important factor affecting obesity; however, it remains a challenge to identify consistent biomarkers across geographic locations and perform precisely targeted modulation for obese individuals. RESULTS: This study proposed a systematic machine learning framework and applied it to 870 human stool metagenomes across five countries to obtain comprehensive regional shared biomarkers and conduct a personalized modulation analysis. In our pipeline, a heterogeneous ensemble feature selection diagram is first developed to determine an optimal subset of biomarkers through the aggregation of multiple techniques. Subsequently, a deep reinforcement learning method was established to alter the targeted composition to the desired healthy target. In this manner, we can realize personalized modulation by counterfactual inference. Consequently, a total of 42 species were identified as regional shared biomarkers, and they showed good performance in distinguishing obese people from the healthy group (area under curve (AUC) =0.85) when demonstrated on validation datasets. In addition, by pooling all counterfactual explanations, we found that Akkermansia muciniphila, Faecalibacterium prausnitzii, Prevotella copri, Bacteroides dorei, Bacteroides eggerthii, Alistipes finegoldii, Alistipes shahii, Eubacterium sp. _CAG_180, and Roseburia hominis may be potential broad-spectrum targets with consistent modulation in the multi-regional obese population. CONCLUSIONS: This article shows that based on our proposed machine-learning framework, we can obtain more comprehensive and accurate biomarkers and provide modulation analysis for the obese population. Moreover, our machine-learning framework will also be very useful for other researchers to further obtain biomarkers and perform counterfactual modulation analysis in different diseases.

Evolution of vegetation and climate variability on the Tibetan Plateau over the past 1.74 million years.

The Tibetan Plateau exerts a major influence on Asian climate, but its long-term environmental history remains largely unknown. We present a detailed record of vegetation and climate changes over the past 1.74 million years in a lake sediment core from the Zoige Basin, eastern Tibetan Plateau. Results show three intervals with different orbital- and millennial-scale features superimposed on a stepwise long-term cooling trend. The interval of 1.74-1.54 million years ago is characterized by an insolation-dominated mode with strong ~20,000-year cyclicity and quasi-absent millennial-scale signal. The interval of 1.54-0.62 million years ago represents a transitional insolation-ice mode marked by ~20,000- and ~40,000-year cycles, with superimposed millennial-scale oscillations. The past 620,000 years are characterized by an ice-driven mode with 100,000-year cyclicity and less frequent millennial-scale variability. A pronounced transition occurred 620,000 years ago, as glacial cycles intensified. These new findings reveal how the interaction of low-latitude insolation and high-latitude ice-volume forcing shaped the evolution of the Tibetan Plateau climate.