Front Cover: Short‐Chain Fatty Acids Produced by Ruminococcaceae Mediate α‐Linolenic Acid Promote Intestinal Stem Cells Proliferation

Xie, Jing; Li, Lingfei; Dai, Tianyi; Qi, Xin; Wang, Yan; Zheng, Tiao‐zhen; Gao, Xiaoyu; Zhang, Yun‐juan; Ai, Yu; Ma, Li; Chang, Song‐lin; Luo, Feng‐xian; Tian, Yang; Sheng, Jun

doi:10.1002/mnfr.202270001

Cited by 2 publications

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“…First, f_ Ruminococcaceae and f_S24-7 bacteria decreased in both the meropenem and imipenem groups but not in the ertapenem group. The two bacteria can produce short-chain fatty acids (SCFAs) and it has been reported that SCFAs play an important role in the colonization resistance of the gut microbiota against pathogens by coordinating key regulatory factors in the host immune response, regulating intestinal barrier function, or altering the intracellular pH of pathogenic bacteria ( 17 – 20 ). Second, Akkermansia spp.…”

Section: Discussionmentioning

confidence: 99%

The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae

Kuang,

Yang,

Luo

et al. 2023

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Gut microbiota plays a crucial role in providing colonization resistance against multi-drug resistant organisms including carbapenem-resistant Klebsiella pneumoniae (CRKP). However, the impact of different carbapenems on intestinal colonization resistance against CRKP remains poorly understood. In this study, we aimed to investigate the effects of three commonly used carbapenems (meropenem, imipenem, and ertapenem) administered at single-day doses, which are typically employed in emergency departments for managing infected patients, on CRKP gut colonization. We conducted experiments in mice by intravenously administering each carbapenem using human-simulated one-day regimens. The composition of the gut microbiota was analyzed using 16S rRNA amplicon sequencing before and after carbapenem administration. Our results revealed that all three carbapenems, when administered at a single-day dose significantly altered the abundance and diversity of the gut microbiota, leading to compromised colonization resistance against CRKP. Notably, the ertapenem and imipenem groups showed an increase in Allobaculum , Bifidobacterium , Enterobacteriaceae , while the meropenem and imipenem groups exhibited a decrease in Ruminococcaceae , S24-7, and Akkermania . Additionally, the Shannon index exhibited a negative correlation with both the number of days of CRKP colonization CFUs and the duration of bacteria shedding. Furthermore, the count of CRKP in mice after ertapenem administration on the first day and the duration of CRKP shedding were significantly lower compared to meropenem and imipenem. Predictive metabolic pathway analysis demonstrated that the three carbapenems similarly affected a range of metabolic pathways of gut microflora, including carbohydrate metabolism and vitamin B. Our findings emphasize that ertapenem, with its relatively narrow spectrum, minimizes perturbations of the gut microbiota and has a relatively less impact on gut colonization resistance against CRKP. IMPORTANCE The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.

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Section: Discussionmentioning

confidence: 99%