Fecal 16S rRNA Gene Sequencing Analysis of Changes in the Gut Microbiota of Rats with Low-Dose Aspirin-Related Intestinal Injury

Abstract

Background. The incidence of small intestinal injury caused by low-dose aspirin (LDA) is high, but the pathogenesis and intervention measures of it have not been elucidated. Recent studies have found gut microbiota to be closely associated with onset and development of NSAID-induced intestinal injury. However, studies of the changes in the gut microbiota of rats with LDA-related intestinal injury have been lacking recently. In this study, we investigated fecal 16S rRNA gene sequencing analysis of changes in the gut microbiota of rats with LDA-related intestinal injury. Methods. Sprague-Dawley (SD) rat models of small intestinal injury were established by intragastric administration of LDA. The small intestinal tissues and the fecal samples were harvested. The fecal samples were then analyzed using high-throughput sequencing of 16S rRNA V3-V4 amplicons. The gut microbiota composition and diversity were analyzed and compared using principal coordinate analysis (PCoA), nonmetric multidimensional scaling (NMDS) analysis, the unweighted pair-group method with arithmetic mean (UPGMA) clustering analysis, multivariate statistical analysis (ANOSIM, MetaStats, and LEfSe), and spatial statistics. Results. The LDA rat model was successfully established. Decreased Firmicutes and increased Bacteroidetes abundances in rats with LDA-induced small intestinal injury were revealed. MetaStats analysis between the before administration of LDA (CG) and after administration of LDA (APC) groups showed that the intestinal floras exhibiting significant differences ( P < 0.05 , q < 0.1 ) were Firmicutes, Bacteroides, Cyanobacteria, Melainabacteria, Coriobacteriia, Bacteroidia, Bacteroidales, Eubacteriaceae, and Streptococcaceae. In addition, the bacterial taxa showing significant differences between the control (NS) and APC groups were Firmicutes, Bacteroides, Verrucomicrobiaceae and Peptococcaceae. Conclusions. The alterations in the gut microbiota composition and diversity of rats with LDA-related intestinal injury were found in the present study. The change of gut microbiota in LDA-related intestinal injury will lay the foundation for further research on the function and signaling pathways of the intestinal flora and promote the use of intestinal flora as drug targets to treat LDA-induced small intestinal injury.

NSAID-Associated Small Intestinal Injury: An Overview From Animal Model Development to Pathogenesis, Treatment, and Prevention

“…Then they tried to give high-dose aspirin to mice and found that the antrum was more prone to develop a severe injury, but small intestinal lesions were mild ( Satoh and Urushidani, 2016 ). Oral administration of aspirin (10.41 mg/kg/d) for 14 days only induced intestinal scattered erosions in SD rats ( Chi et al, 2021 ). Aspirin does not appear to cause severe damage to the intestinal mucosa of experimental animals.…”

“…In addition, animal models play a significant role in exploring effective therapeutic and preventive measures and analyzing therapeutic modalities’ possible mechanisms of action. Researchers have successfully used a wide variety of NSAIDs to establish disease models in rodents, including indomethacin ( Kawashima et al, 2020 ; Kuzumoto et al, 2021 ; Tawfik et al, 2016 ; Yamada et al, 1993 ), diclofenac ( Beck et al, 1990 ; Chen et al, 2021 ; Xu et al, 2021 ), aspirin ( Bouzenna et al, 2019 ; Brodie et al, 1970a ; Chi et al, 2021 ), flurbiprofen ( Campanella and Jamali, 2009 ), naproxen ( Carvalho et al, 2015 ; Nicolau et al, 2017 ), loxoprofen ( Hayashi et al, 2013 ; Satoh and Urushidani, 2016 ), ibuprofen ( Beck et al, 1990 ; Lu et al, 2018 ), diflunisal ( Niu et al, 2014 ), BFMeT ( Hagiwara et al, 2004 ; Uejima et al, 1996 ), paracetamol ( Chopyk et al, 2019 ; Niu et al, 2020 ), Ketoprofen ( Cheng et al, 2014 ; Saitta et al, 2014 ). Many experimental articles have verified the reproducibility and stability of various modeling modalities.…”

Impact of concurrent medications on the outcome of immunotherapy in non‐small cell lung carcinoma

“…18 NSAIDs have been reported to be associated with alterations in microbial populations. [19][20][21] In this study, patients using NSAIDs had a significantly worse ORR and PFS in univariate analysis. The impact of NSAIDs on the gut microbiota may affect the outcomes.…”

Meta-analysis of the effect of probiotics or synbiotics on the risk factors in patients with coronary artery disease

“…Most of the existing meta-analyses do not restrict the disease population. In contrast, certain coronary drugs, such as aspirin (27) and atorvastatin (28), have been found to modulate the intestinal flora, which might diminish the impact of probiotics on the intestinal flora. Furthermore, the absence of a standardized dietary structure among patients is a crucial factor influencing the outcomes of intestinal flora changes.…”