Effect of fecal microbiota transplantation in patients with slow transit constipation and the relative mechanisms based on the protein digestion and absorption pathway

Abstract

Background Fecal microbiota transplantation (FMT) is considered an effective treatment for slow transit constipation (STC); nevertheless, the mechanism remains unclear. Methods In this study, eight patients with STC were selected according to the inclusion and exclusion criteria; they then received three treatments of FMT. The feces and serum of STC patients were collected after each treatment and analyzed by integrating 16 s rRNA microbiome and metabolomic analyses. Results The results showed that the percentage of clinical improvement reached 62.5% and the rates of patients’ clinical remission achieved 75% after the third treatment. At the same time, FMT improved the Wexner constipation scale (WCS), the Gastrointestinal Quality-of-Life Index (GIQLI) and Hamilton Depression Scale (HAMD). Fecal microbiome alpha diversity and beta diversity altered significantly after FMT. Analysis of the 16 s rRNA microbiome showed that the numbers of Bacteroidetes (Prevotell/Bacteroides) and Firmicute (Roseburia/Blautia) decreased, whereas Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Firmicute (Lactobacillus) increased after FMT. The metabolomics analyses showed that the stool of FMT-treated patients were characterized by relatively high levels of N-Acetyl-L-glutamate, gamma-L-glutamyl-L-glutamic acid, Glycerophosphocholine, et al., after FMT. Compared with baseline, the serum of treated patients was characterized by relatively high levels of L-Arginine, L-Threonine, Ser-Arg, Indoleacrylic acid, Phe-Tyr, 5-L-Glutamyl-L-alanine, and lower levels of Erucamide after the treatment. The correlation analysis between the metabolites and gut microbiota showed a significant correlation. For example, L-Arginine was positively correlated with lactobacillus, et al. L-Threonine was positively correlated with Anaerovibrio, Sediminibacterium but negatively correlated with Phascolarctobacterium. Erucamide had significant negative correlations with Sediminibacterium and Sharpea, while being positively correlated with Phascolarctobacterium. Enriched KEGG pathways analysis demonstrated that the protein digestion and absorption pathways gradually upregulated with the increase of FMT frequency. The L-Arginine and L-Threonine were also involved in the pathway. A large amount of Na + was absorbed in the pathway, so that it might increase mucus secretion and electrical excitability of GI smooth muscle. Conclusions Therefore, we speculated that FMT changed the patients’ gut microbiota and metabolites involved in the protein digestion and absorption pathways, thereby improving the symptoms of STC. Study on the effectiveness and safety of FMT in the treatment of STC. The study was reviewed and approved by Ethics Committee of Tianjin People's Hospital (ChiCTR2000033227) in 2020.

Role of gut microbiota-derived signals in the regulation of gastrointestinal motility

“…In contrast, FMT derived from constipated donors delays GI transit time in mice (47). In clinical practice, FMT improves the symptoms of slow transit constipation patients by modulating gut microbiota and metabolites involved in the protein digestion and absorption pathways (48). These data suggest that regulating the gut microbiota may be a novel therapeutic strategy for GI dysmotility.…”

Association between fecal short-chain fatty acid levels and constipation severity in subjects with slow transit constipation

“…Bifidobacterium is well known as the primary source of producing acetic acid [19], and Lactobacillus has been proved to increase the level of butyric acid by interacting with other gut microbiota [20]. Fecal microbiota transplantation or the supplement of beneficial bacteria may remit constipation and abdominal symptoms [18,21], which might be associated with altered SCFAs. Therefore, the microbiota-derived SCFAs can promote the gut health and gastrointestinal motility.…”

Causal associations between human gut microbiota and hemorrhoidal disease: A two-sample Mendelian randomization study

“…[ 29 ] After fecal microbiota transplantation, patients with slow-transit constipation have lower serum erucamide level, which is negatively correlated with Phascolarctobacterium . [ 30 ]…”

“…[29] After fecal microbiota transplantation, patients with slow-transit constipation have lower serum erucamide level, which is negatively correlated with Phascolarctobacterium. [30] In patients with hepatic encephalopathy, the gut microbiota is characterized by an overgrowth of Burkholderiales and several other bacteria, capable of producing byproducts that may be neurotoxic, [31] and these byproducts are also associated with epilepsy. [32] It is still uncertain whether these metabolites affect neuromuscular motility, which is also a cause of HEM.…”