Background
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic and recurrent inflammatory disorders with uncertain etiology [
1]. IBD are generally accompanied by abdominal pain, weight loss, and diarrhea, and can result in complete obstruction of the gastrointestinal (GI) tract [
2]. Worldwide, the incidence and prevalence of IBD have increased over the past few decades. To date, the precise pathogenesis of IBD remains unclear, although dysfunction of the immune system due to interactions between a host’s response to microbial flora in the gut may be one of the main factors that contribute to these diseases [
3].
Hunan gut microbiota consists of more than 100 trillion microorganisms, which is ten times more than the total number of human cells in the body [
4]. In general, a fetus grows in a sterile environment in the uterus. Then, after birth, gut colonization starts rapidly and it is influenced by a variety of factors, including diet, antibiotics, and stress [
5]. Gut microbiota have diverse and useful functions in energy balance, glucose metabolism, drug metabolism, and inflammation in a host [
6]. However, when an imbalance in normal gut microbiota occurs, this is known as dysbiosis. Dysbiosis underlies the pathogenesis of numerous diseases, including IBD, colorectal cancer, and metabolic syndrome in connection with host metabolism [
7,
8]. For obese individuals, their intestinal microbiota contains a higher proportion of
Firmicutes, and a lower proportion of
Bacteriodetes compared to lean individuals [
9,
10]. Insulin sensitivity and plaque synthesis in blood vessels can also be altered by gut microbiota [
9,
11]. Furthermore, changes in the population and metabolism of the diverse bacteria population in a GI tract can affect systemic inflammation and the function of neurotransmitters in the brain [
12,
13].
Gut microbiota plays a critical role in anti-inflammatory and immune-regulatory function, and thus, potentially represent an attractive IBD therapy. Various therapies that target restoration of the gut microbiota by altering their composition have been suggested, including fecal microbiota transplantation, probiotics, prebiotics, antibiotics, and dietary intervention. Recent interest in the dietary phytonutrients that are present in natural herbs has led to investigations of their potential impact on human health. For example, the polyphenols present in various natural herbs have been reported to modulate the composition and numbers of gut microbiota and to indirectly influence metabolism and the bioavailability of gut microbiota [
14]. Another key benefit that has been found is an absence of undesirable side effects. Thus, gut microbiota may represent a potential therapeutic strategy for IBD and may help maintain intestinal function [
15].
Sasa quelpaertensis Nakai is an edible dwarf bamboo grass that inhabits the area surrounding Mt Halla on Jeju Island in Korea. Its leaf extract has been reported to mediate various health promoting properties, including anti-inflammation, anti-cancer effects, and anti-obesity effect [
16‐
18].
Sasa quelpaertensis leaves extract (SQE) is a mixture of polysaccharides, amino acids, and polyphenols, including
p-coumaric acid and tricin, and has exhibited anti-inflammatory and anti-obesity effects [
19,
20]. In particular, SQE has been found to mediate anti-inflammatory effects by regulating inflammatory mediators such as nitric oxide, tumor necrosis factor α, and COX-2 both in vivo and in vitro [
17]. However, there is limited evidence regarding the effect of SQE on gut microbiota during inflammation.
Therefore, in the present study, the ability of SQE to regulate inflammation by modulating microbial composition in a dextran sulfate sodium (DSS)-induced colitis animal model was evaluated using high-throughput sequencing of the 16S ribosomal rRNA (rRNA) gene.
Discussion
The human gut contains a large population of diverse and complex enteric microbiota. Tremendous changes in the diversity and composition of this community, as well as the metabolic function of the gut microbiota, have been related to IBD [
27,
28]. In particular, gut microbiota have been identified as a critical factor in IBD. Correspondingly, short-term antibiotic treatment for IBD patients have been used to suppress intestinal inflammation [
29,
30]. Using murine model in gut microbiota study has been allowed functional and metabolic research on host-microbe interactions, and has brought more insights into the pathological mechanisms of IBD [
31]. In colitis mouse model, the major gut microbiota shifted and gut bacterial diversity was reduced similar to those found in human IBD [
32,
33].
Previously, it was reported that SQE treatment modulated the levels of proinflammatory markers, while also regulated the activation of nuclear factor κB and oxidative stress, in animal models of DSS-induced colitis [
17,
34]. In the present study, the goal was to understand the effect of SQE on dysbiosis of microbiota in DSS-induced colitis. Therefore, overall differences in the microbial community, as well as modifications of microbiota composition after SQE treatment were investigated by using barcoded pyrosequencing of the 16S rRNA gene. The results obtained demonstrate that the microbial community profiles of the experimental groups examined were altered by DSS treatment, and dysbiosis of gut microbiota was improved with SQE supplementation.
In animal models of IBD, DAI value and colonic length are key indicators for evaluating the severity of colitis [
35,
36]. Consistent with the results of a previous study [
17], SQE supplementation attenuated the severity of colitis by lowering the DAI value and extending the length of the colon. In contrast, changes in the colon epithelium and higher DAI values characterized in the DSS group compared with the control group,
Modification to the composition of a microbial community may involve changes in diversity and in bacterial metabolism. Furthermore, an imbalance between obligate anaerobic bacteria and facultative anaerobic bacteria can occur, and this is related to the inflammation process [
37,
38]. For example, Ott et al. reported that a microbial shift due to an increased in gram-negative bacteria accompanied a reduction in bacterial diversity in IBD patients, and this led to abnormalities in the inflammatory process [
39]. In the present study, the analysis of various alpha diversity indices indicated that a reduction in bacterial diversity occurred in the DSS group compared to the control and SQE groups. In addition, the gut microbial communities of the DSS group were characterized by a clustered distance to the control group. The latter result is consistent with the results of previous studies where microbial divergence manifested as relative abundance shift in cases of IBD [
39,
40]. However, in the present study, SQE supplementation recovered the bacterial diversity of the gut and greater clustering of the gut microbial communities close to the control group was observed compared to the DSS group. Taken together, these results suggest that SQE may help the gut microbiota to maintain their composition, community, microbial evenness, and richness.
Interactions between gut microbiota and the host immune system play an important role in the development of a host’s immune system [
41]. Generally, the composition of gut microbiota remains stable during adulthood, and it can undergo dynamic changes in response to environmental stresses or diet. Such alterations in composition may influence health or disease risk [
42]. The taxonomic compositions of the gut microbiota in humans is similar to that observed in mice at the phylum level [
43]. Dysbiosis in patients with IBD has been characterized as an increase in the ratio of
Bacteroidetes/
Firmicutes [
28,
44]. In the present study, the ratio of
Bacteroidetes/
Firmicutes was significantly higher in the DSS group than in the control group, whereas this ratio in the SQE group was similar to that of the control group. It was also observed that the proportion of
Firmicutes was significantly decreased following DSS treatment, yet the proportion recovered to control levels following SQE supplementation. The
Firmicutes phylum modulates the pH of the colonic and inhibits the growth of pathogens by metabolizing short-chain fatty acids (SCFAs) and producing butyrate in the intestinal mucosa. Butyrate is a key energy source for epithelial cells of the colon and it suppresses pro-inflammatory cytokines in the gut [
45]. At the class level, an increase in
Bacteroidia (phylum
Bacteroidetes) and
Gammaproteobacteria, as well as a reduction in
Clostridia (phylum
Firmicutes) was observed in the DSS group compared to the control group.
Gammaproteobacteria, a bacteria that can induce acute intestinal inflammation, was also significantly increased in the DSS group, thereby indicating that changes in intestinal permeability and induction of chronic systemic inflammation had occurred [
46]. However, these changes in the composition of the microbial community were reduced in the SQE group compared to the DSS group, which suggested that SQE was able to regulate a gut microbial community by modulating gut inflammation.
In patients and experimental animal models with IBD, the relative abundance of
Lachnospiraceae was reduced and the proportion of the
Bacteroidaceae is relatively increased [
47].
Lachnospiraceae plays an important role in fermenting SCFAs that derived from carbohydrates [
48]. Another bacteria,
Ruminococcaceae performs the first step in carbohydrate metabolism where hydrogen is consumed to butyrate. Microbial metabolisms of SCFAs is associated with gut motility and intestinal transit time, as well as with the function of histone deacetylases and the nervous system [
49]. In the present study, the compositional abundances of
Lachnospiraceae,
Bacteroidaceae, and
Ruminococcaceae, which mediate SCFA metabolism, were altered in mice of the DSS group. In contrast, microbial dysbiosis was improved in the SQE group compared with the DSS group. Previously, it was reported that SQE facilitated gut motility in the DSS-induced colitis mouse model [
34], and this explains the role of SQE in the metabolisms of SCFAs and microbial composition related to intestinal function.
Enterobacteriaceae (genus
Enterobacter)
, obligate anaerobic bacteria for the metabolism of high energy nutrients, is present in greater number during inflammation [
50]. In the present study, an increase in the proportion of
Enterobacteriaceae was consistently detected in the DSS group compared with the control group, and this increase was blocked with administration of SQE.
As presented above, a strong connection between gut microbiota and the intestinal immune system has been observed. Among the various microbacteria,
Clostridium (species
Clostridium cocleatum) and
Bacteroides (species
Bacteroides acidifaciens,
Bacteroides_uc) have been reported to induce the emission of regulatory T cells and to reduce intestinal inflammation [
51]. In the present study, higher proportion of the
Clostridium and
Bacteroides were detected in the DSS group compared with to the control group, and these increase suggest that prevention of intestinal inflammation by specific groups of commensal obligate anaerobic bacteria may mediate direct protective effects for pathogens. Furthermore, the balance of microbial composition of species affects the bile acid metabolism in the colon. In particular,
Enterobacter,
Bacteroides, and
Clostridium absorb dietary fats, facilitate lipid absorption, and maintain intestinal barrier function [
52]. Consequently, dysbiosis resulting from intestinal inflammation can affect the function of bacteria and the other metabolic processes.
Many polyphenols contribute to important biological activities, including antioxidant, anticarcinogenic, and antimicrobial activities that are associated with pathological disease processes [
53,
54]. In addition, most polyphenols are consumed and ingested, after being metabolized by gut microbiota, which leads to greater biological activity and increased bioavailability compared with their predecessors [
55]. Furthermore, polyphenol intake may have a direct impact on the composition of gut microbiota and the functionality and the growth of certain bacterial species. For example, in the presence of phenolic compounds, the
Firmicutes/
Bacteroidetes ratio in the microbiota of obese individuals was found to be altered, and polyphenol-rich grape seed extract has been found to contain a higher proportion of
Lactobacillus/
Enterococcus bacteria [
56,
57]. Several studies have also shown that natural herbs and polyphenols help to improve intestinal inflammation in colitis model [
58]. SQE has shown beneficial effects on colitis in previous studies. Moreover, the bioactive component of SQE, tricin and
p-coumaric acid, have exhibited antioxidant, anti-inflammatory, and anticancer effects which remain to be investigated in relation to gut microbiota [
17,
18,
20,
34].
The identification of host and microbial interactions in IBD patients, as well as a greater understanding of the role of the microbiome and the changes in its composition that occur in the disease states of IBD, should lead to the development of highly effective and nontoxic targeted interventions to correct underlying abnormalities and induce sustained therapeutic responses. Currently, broad spectrum antibiotics, probiotics, and prebiotics are used to prevent and treat IBD [
59]. The present results suggest a possible role for SQE and its various of polyphenols in the clinical treatments of IBD via regulation of gut microbiota dysbiosis and diversity. Moreover, the use of SQE would represent a natural therapeutic strategy for IBD patients. However, a clinical intervention trial is needed to confirm the present results in IBD patients, while additional research is needed to understand the relationship between dietary polyphenols and gut microbiota.