The human gut is colonized by commensal microorganisms, predominately bacteria that have coevolved in symbiosis with their host. The gut microbiota has been extensively studied in recent years, and many important findings on how it can regulate host metabolism have been unraveled. In healthy individuals, feeding timing and type of food can influence not only the composition but also the circadian oscillation of the gut microbiota. Host feeding habits thus influence the type of microbe‐derived metabolites produced and their concentrations throughout the day. These microbe‐derived metabolites influence many aspects of host physiology, including energy metabolism and circadian rhythm. Peroxisome proliferator‐activated receptors (PPARs) are a group of ligand‐activated transcription factors that regulate various metabolic processes such as fatty acid metabolism. Similar to the gut microbiota, PPAR expression in various organs oscillates diurnally, and studies have shown that the gut microbiota can influence PPAR activities in various metabolic organs. For example, short‐chain fatty acids, the most abundant type of metabolites produced by anaerobic fermentation of dietary fibers by the gut microbiota, are PPAR agonists. In this review, we highlight how the gut microbiota can regulate PPARs in key metabolic organs, namely, in the intestines, liver, and muscle. Knowing that the gut microbiota impacts metabolism and is altered in individuals with metabolic diseases might allow treatment of these patients using noninvasive procedures such as gut microbiota manipulation.—Oh, H. Y. P., Visvalingam, V., Wahli, W. The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology. FASEB J. 33, 9706–9730 (2019). www.fasebj.org

Antibiotics lead to increased susceptibility to colonization by pathogenic organisms, with different effects on the host-microbiota relationship. Here, we show that metronidazole treatment of specific pathogen-free (SPF) mice results in a significant increase of the bacterial phylum Proteobacteria in fecal pellets. Furthermore, metronidazole in SPF mice decreases hind limb muscle weight and results in smaller fibers in the tibialis anterior muscle. In the gastrocnemius muscle, metronidazole causes upregulation of Hdac4, myogenin, MuRF1, and atrogin1, which are implicated in skeletal muscle neurogenic atrophy. Metronidazole in SPF mice also upregulates skeletal muscle FoxO3, described as involved in apoptosis and muscle regeneration. Of note, alteration of the gut microbiota results in increased expression of the muscle core clock and effector genes Cry2, Ror-β, and E4BP4. PPARγ and one of its important target genes, adiponectin, are also upregulated by metronidazole. Metronidazole in germ-free (GF) mice increases the expression of other core clock genes, such as Bmal1 and Per2, as well as the metabolic regulators FoxO1 and Pdk4, suggesting a microbiota-independent pharmacologic effect. In conclusion, metronidazole in SPF mice results in skeletal muscle atrophy and changes the expression of genes involved in the muscle peripheral circadian rhythm machinery and metabolic regulation.

Living organisms display internal biological rhythms, which are an evolutionarily conserved adaptation to the environment that drives their rhythmic behavioral and physiological activities. The gut microbiota has been proposed, in association with diet, to regulate the intestinal peripheral clock. However, the effect of gut dysbiosis on liver remains elusive, despite that germfree mice show alterations in liver metabolic functions and the hepatic daily rhythm. We analyzed whether the disruption of gut microbial populations with various antibiotics would differentially impact liver functions in mice. Our results support the notion of an impact on the hepatic biological rhythm by gram-positive bacteria. In addition, we provide evidence for differential roles of gut microbiota spectra in xenobiotic metabolism that could protect against the harmful pharmacological effects of drugs. Our results underscore a possible link between liver cell proliferation and gram-positive bacteria.

Dengue remains a public health concern in Singapore, with endemic transmission and recurring outbreaks. This study presents results from a Singapore-focused subgroup of the Growth and Emerging Markets Knowledge, Attitudes, and Practices (GEMKAP) cross-sectional survey, which assessed public Knowledge, Attitudes, and Practices (KAP) levels related to dengue and prevention. A total of 400 adult respondents from Singapore participated in an online survey conducted between September and October 2022. Overall KAP scores were 48% (Knowledge), 61% (Attitudes), and 36% (Practices). Awareness of dengue transmission was widespread (96% identified mosquitoes as the vector and 97% recognised stagnant water breeding), while fewer respondents recognised the availability of a dengue vaccine (23%) or the absence of a medicinal cure (38%). Trust in the government’s dengue control efforts was high, though respondents practised an average of 5.1 out of 10 recommended prevention measures. Of the respondents, 25% had a high willingness to vaccinate against dengue. Multivariate analysis revealed that positive vaccine perceptions, past dengue experience, automatic motivation, and social opportunity were associated with willingness to vaccinate. Respondents supported a multi-pronged dengue management approach combining education, vector control, and vaccination. Future efforts should integrate behaviour change strategies, enhance multi-stakeholder collaboration, and empower communities to ensure sustainable impact.