Real-time localization and microbial activity information of indigenous gut microbiota over an extended period of time remains a challenge with existing visualizing methods. Here, we report a metabolic fluorine labeling (MEFLA)–based strategy for monitoring the dynamic gut microbiota via 19 F magnetic resonance imaging ( 19 F MRI). In situ labeling of different microbiota subgroups is achieved by using a panel of peptidoglycan-targeting MEFLA probes containing 19 F atoms of different chemical shifts, and subsequent real-time in vivo imaging is accomplished by multiplexed hotspot 19 F MRI with high sensitivity and unlimited penetration. Using this method, we realize extended visualization (>24 hours) of native gut microbes located at different intestinal sections and semiquantitative analysis of their metabolic dynamics modulated by various conditions, such as the host death and different β-lactam antibiotics. Our strategy holds great potential for noninvasive and real-time assessing of the metabolic activities and locations of the highly dynamic gut microbiota.
Inflammation-related diseases affect large populations of people in the world and cause substantial healthcare burdens, which results in significant costs in time, material, and labor. Preventing or relieving uncontrolled inflammation is critical for the treatment of these diseases. Herein, we report a new strategy for alleviating inflammation by macrophage reprogramming via targeted reactive oxygen species (ROS) scavenging and cyclooxygenase-2 (COX-2) downregulation. As a proof of concept, we synthesize a multifunctional compound named MCI containing a mannose-based macrophage targeting moiety, an indomethacin (IMC)-based segment for inhibiting COX-2, and a caffeic acid (CAF)-based section for ROS clearance. As revealed by a series of in vitro experiments, MCI could significantly attenuate the expression of COX-2 and the level of ROS, leading to M1 to M2 macrophage reprogramming, as evidenced by the reduction and the elevation in the levels of pro-inflammatory M1 markers and anti-inflammatory M2 markers, respectively. Furthermore, in vivo experiments show MCI′s promising therapeutic effects on rheumatoid arthritis (RA). Our work illustrates the success of targeted macrophage reprogramming for inflammation alleviation, which sheds light on the development of new anti-inflammatory drugs.
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