Roseburia spp. have been brought to the fore because of their novel role in modulating the gut microbial ecology, immune responses, and the development of human disorders (Tamanai-Shacoori et al., 2017). Roseburia was named in honor of Theodor Rosebury, an American microbiologist, for his groundbreaking contributions to the field of oral microbiome. Roseburia sp. belongs to the phylum Firmicutes, class Clostridia, order Clostridiales, and family Lachnospiraceae (Stackebrandt, 2014). The Roseburia genus has five well-characterized species (Roseburia intestinalis, Roseburia hominis, Roseburia inulinivorans, Roseburia faecis, and Roseburia cecicola), all of which produce short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate (Tamanai-Shacoori et al., 2017). In 2002, Duncan et al. isolated a strain of anaerobic, Gram-positive, slightly curved rod-shaped, and flagellated bacteria from human fecal samples. Subsequent phylogenetic analysis revealed its intimate similarity with R. cecicola and the members of cluster XIVa of Clostridium subphylum; thus, it was named Roseburia intestinalis (Duncan et al., 2002). Among the top 20 most abundant bacteria in the gut microbiome, the R. intestinalis cluster usually accounts for 0.9%–5.0% (mean = 2.3%) of the total microbiota (Hold et al., 2003; Hiippala et al., 2018).

R. intestinalis are obligate anaerobes that are difficult to culture. They were firstly isolated from human feces in an M2 medium-based culture system (Louis et al., 2004). It was reported that R. intestinalis XB6B4 can be cultivated under anaerobic conditions at 37°C in a complex medium containing clarified rumen fluid (described in Chassard et al., 2007) and 0%–5% complex substrates (oat spelt xylan, wheat or corn bran, pea fiber, cabbage, and leek) or 0%–3% sugar (xylose or glucose) (Chassard et al., 2007; Mirande et al., 2010). R. intestinalis DSM 14610 was reported to degrade and utilize oligofructose as the sole energy source, but only when acetate was added to a special medium for colon bacteria (Falony et al., 2006). This bacterium can also grow anaerobically at 37°C in lytic/10 anaerobic/F medium or LYBHI medium supplemented with yeast extract, cellobiose, maltose, and cysteine (Zhu, C. et al., 2018; Cornuault et al., 2020). Butyryl-CoA:acetate CoA transferase is the key enzyme that produces butyrate in butyrate-producing bacteria. This enzyme has been detected in R. intestinalis, which endows it with the ability to utilize acetate in order to produce butyrate (Pryde et al., 2002). Previous studies have found that R. intestinalis and Faecalibacterium prausnitzii are the most abundant butyrate-producing bacteria in human feces (Hold et al., 2003; Duncan et al., 2004). R. intestinalis can ferment fibers to produce butyrate in an M2 medium supplemented with wheat starch (Louis et al., 2004). Of note is that butyrate has been reported to exert pervasive anti-inflammatory and metabolic modulation effects in different disease models (Canfora et al., 2015; McNabney and Henagan, 2017). Therefore, R. intestinalis can be applied as a potential probiotic given its ability to produce butyrate. Enteric bacteria use fibers as a source of carbon to produce butyrate. Martinez et al. reported that a whole-grain diet increases the intestinal abundance of R. intestinalis and improves the concentration of interleukin-6 (IL-6, which is linked to metabolic dysfunctions) (Martinez et al., 2013). R. intestinalis also has the ability to ferment xylan and β-mannan, which are common fiber ingredients in the diet (Mirande et al., 2010; Leth et al., 2018; La Rosa et al., 2019). β-mannans and xylans are important components of the plant cell wall, and they are acetylated to protect them from degradation by glycoside hydrolases. β-mannans are widely present in human and animal diets. RiCE2 and RiCE17, two carbohydrate esterases from R. intestinalis, remove acetylations from all positions in complex β-mannans in a complementary manner (Michalak et al., 2020). The growth of R. intestinalis is influenced by the carbon source, symbiont, and anoxia, and also by the pH. It has been discovered that iron can modulate the ability of R. intestinalis to produce butyrate through the pyruvate mechanism: ferredoxin oxidoreductase (PFO) can convert pyruvate to acetyl-CoA (Dostal et al., 2015). In addition, PFO is sensitive to reducing ferredoxin (Dostal et al., 2015). These data show that R. intestinalis uses different carbohydrates as the source of energy and that its growth is susceptible to iron. The human regenerating family member 3 alpha (hREG3α) promotes the growth of R. intestinalis by inhibiting reactive oxygen species (ROS) signaling and induces resistance in mice with dextran sulfate sodium (DSS)-induced colitis (Darnaud et al., 2018). Colonic bacteria compete for the colonic ecological niche through nutrition plunder and preempt niche advantage (Leth et al., 2020). Several external factors, such as diet or antibiotic use, and endogenous factors may affect the ecological niche of R. intestinalis. It has been reported that ultravirulent phage mutants can drive the disruption of R. intestinalis and the ecological niche occupied by other resistant bacteria (Cornuault et al., 2020). This phenomenon reveals that the interactions among bacteria in the gut environment are complex. The structural characteristic of the flagella in R. intestinalis regulates its motion. The flagella help R. intestinalis to penetrate the colonic mucus layer in order to interact with the epithelium. Therefore, R. intestinalis is one of the most abundant butyrate-producing bacteria that adhere to intestinal mucin, facilitating its significant advantages for the probiotic role (Van den Abbeele et al., 2013).

According to the guidelines from the World Health Organization (WHO) on the Evaluation of Probiotics in Food issued in 2002, probiotics are viable microorganisms in dietary supplements that, when consumed at certain levels, stabilize the gastrointestinal tract microflora and confer health benefits to the consumer. In addition to our attempts to expand knowledge about R. intestinalis ( Table 1 and Figure 1 ), multiple trials and experiments based on animal models have elaborated the complicated and tight relationship between R. intestinalis and the occurrence of human diseases ( Figure 2 ). Accumulating evidence also supports the probiotic effect of R. intestinalis in the human body, which demonstrates its fundamental benefits in maintaining a healthy homeostasis. However, the vast majority of the studies described the role of R. intestinalis through microbiome and metabolomics analyses ( Table 2 ). R. intestinalis frequently appears in the list of significantly variable bacteria of different diseases and has been shown to have a beneficial role. Numerous studies have also elucidated the effect of R. intestinalis on immunity and pathophysiology. As such, there is a need to clarify the role of R. intestinalis within separate systems.

Autoimmune diseases usually involve multiple systems, including the intestine. Bacteria interact with enteric mucosal immune cells by presenting antigen and chemical signals to organs, such as the thymus, brain, liver, and the pancreas. It is universally accepted that the immune system mounts a response to invaders. Usually, autoimmune diseases have complicated pathogenesis associated with gut microbes. According to the sequencing results of the fecal samples obtained from 44 Canadian rheumatic arthritis (RA) patients, Forbes et al. found a decreased Roseburia abundance, which was used to distinguish RA patients from the healthy group in a random forest classification model (Forbes et al., 2018). In addition, the Roseburia genus was a potential marker of health given its butyrate-producing and anti-inflammatory properties (Forbes et al., 2018). Notably, identical lower gut Roseburia abundance phenomena were found in adults with Behçet syndrome and systemic sclerosis, particularly in systemic sclerosis patients with gastrointestinal involvement (Consolandi et al., 2015; Patrone et al., 2017). However, these studies were limited by the small sample size of the cohorts. Elsewhere, a systematic literature review of studies involving the collection of fecal samples from 1,084 patients with chronic rheumatic diseases and healthy controls revealed a decreased number of Roseburia species in enrolled patients (Salem et al., 2019).

Bacteria sometimes imitate autologous antigens to induce autoimmune antibodies. In antiphospholipid syndrome (APS), researchers have discovered cross-reactivity between non-orthologous mimotopes expressed by R. intestinalis and the autoantigen β2-glycoprotein (β2GPI) (Ruff et al., 2019). Besides, the anti-R. intestinalis mimotope immunoglobulin G (IgG) was significantly elevated in APS patients and was correlated with anti-β2GPI IgG autoantibodies. Meanwhile, R. intestinalis gavage could trigger an autoimmune pathology in susceptible mice (Ruff et al., 2019). However, due to R. intestinalis appearing as a type of common gut-friendly bacteria, the specific autoimmune phenotype transformation needs stricter consideration in such a mouse model. Otherwise, the on–off switch may hide in a particular microenvironment. These findings provide strong evidence that R. intestinalis displays beneficial effects in most patients with autoimmune diseases despite the occasionally complicated effects. As such, further exploration is warranted to elucidate the mechanism of the interaction of R. intestinalis with the immune system, an adaptation of immune cells, perception, and evolution with intestinal microbes.

Through dysbiosis-associated Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, researchers have demonstrated that intestinal microbiome dysbiosis alters the commensal remolding and shifts the nutritional metabolism. Accumulating evidence reveals the tight association of butyrate with glucose homeostasis, insulin resistance, and appetite (Canfora et al., 2015). Metabolic diseases are typically multi-nutrition-utilizing disorders and abnormalities of immune-induced hormones. As mentioned above, Roseburia spp. are a critical butyrate-producing bacteria cluster. Several researchers have reported that the potential role of butyrate is by inhibiting histone deacetylase (HDAC) or interacting with G protein-coupled receptors (GPCRs) such as free fatty acid receptors 2 (FFAR2) and 3 (FFAR3) in the control of body weight and insulin sensitivity (Canfora et al., 2015; Morrison and Preston, 2016; McNabney and Henagan, 2017). Butyrate can increase energy expenditure and fat oxidation, thereby exerting a further influence on energy homeostasis and lipid metabolism. Studies have also reported that FFAR 2/3-associated signaling exerts a potential regulatory role for butyrate in glucose homeostasis (Canfora et al., 2015). To date, there is strong evidence on the relationship between R. intestinalis and type 2 diabetes mellitus (T2DM) ( Table 2 ). A metagenome-wide association study (MGWAS) in a large-scale population-based cohort study in China based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. discovered a decreased trend in the abundance of R. intestinalis in T2DM patients (Qin et al., 2012). These results were confirmed in subsequent studies (Tilg and Moschen, 2014). However, the big question is whether different types of diabetes determine the diversity of the gut Roseburia population. Another investigation that evaluated the gut microbiota and metabolism in patients with type 1 diabetes mellitus (T1DM) reported lower R. intestinalis abundance (Leiva-Gea et al., 2018). Furthermore, a systemic review involving 26 studies, including 2,600 children and 189 adults, revealed that the most significant bacterial alterations in T1DM patients involved Roseburia spp. (Jamshidi et al., 2019). Taken together, these findings coincide with the essential role of butyrate in glucose homeostasis. Meanwhile, obesity shares the same difference in gut commensal compositions. A study by (Tims et al., 2013) recruited 40 monozygotic twin pairs and explored the association of microbial signatures with body mass index (BMI). The results revealed the positive correlation between R. intestinalis and BMI; that is, individuals with higher BMI carried more abundant butyrate producers. Another study reported that children and adolescents with primary hyperlipidemia had a lower abundance of Roseburia, suggesting the correlation of the Roseburia genus with the changes in lipidemic parameters (Gargari et al., 2018). These pieces of research demonstrate that R. intestinalis plays an extensively instrumental role in metabolic disorders. However, further studies are warranted to elucidate whether R. intestinalis plays a more pivotal role in metabolic diseases than do widely studied microorganisms, such as Akkermansia muciniphila and Christensenellaceae. Some of the significant shortcomings of metabolism research include the lack of an effective design for primary bacterial culture, identification of animal and cell experimental function, and necessary clinical trials. Perhaps, R. intestinalis will be included in mixed probiotic prescriptions for metabolic disorders in the future.

The microbiota–gut–brain axis modulates the interaction between the nervous system and the intestinal environment. Bacterial composition and bacterial metabolites influence the function of both the enterocytes and exocrine glands. The effects of exocrine molecules on the enteric nervous system are either direct or indirect. Compelling evidence shows that immune cells such as ILC3 can interact with the colonic glia to form a glia–ILC3 axis, whereas microbes, including Roseburia, transmit signals to the colonic glia to stimulate the IL-22 production of ILC3 mediated by glial neurotrophic factors (Bernink et al., 2016; Ibiza et al., 2016). These complicated interaction axes involve microbes, immunity, and nerve. Therefore, gut bacteria such as Roseburia exert a potential impact on the pathogenetic process of nervous system diseases ( Table 2 ). An investigation by Prof. Wei demonstrated that R. intestinalis influenced the 5-HT level and GFAP expression in colonic tissue, alleviating the depression-like behavior in mice (Xu et al., 2021). This piece of evidence supports the role of Roseburia in neural disorders. In another study, the mucosal and fecal 16S rRNA-based assay of patients with Parkinson’s disease (PD) and controls showed that Roseburia was significantly more abundant in controls than in PD patients (Keshavarzian et al., 2015). Additionally, when the fecal microbiota obtained from PD patients or healthy controls were transplanted into germ-free mice via oral gavage, the results indicated that the abundance of Roseburia spp. increased in animals colonized with microbiota from PD patients (Keshavarzian et al., 2015). It was speculated that Roseburia spp.-associated gut dysbiosis promoted the aggregation of α-synuclein via colonic motor defect, and the subsequent specific changes enhanced neuroinflammation and the progression of PD (Sampson et al., 2016). Considering the impact of the transplant on the actual dysbiosis of PD patients, the divergent results should be analyzed carefully and cautiously. Aside from PD, depression is another global neurological concern. Previous evidence indicated a lower abundance of Roseburia in major depressive disorder (MDD) patients than in the matched healthy group (Zheng et al., 2016). In the same study, fecal microbiota transplantation (FMT) from MDD patients to germ-free recipient mice could induce depression-like behaviors. Moreover, the transplanted depression mice were characterized by an enriched carbohydrate and amino acid metabolism (Zheng et al., 2016). Nevertheless, cohort data from a study by Jiang et al. revealed a relatively more abundant Roseburia in active MDD patients than in the healthy group (Jiang et al., 2015). Liu et al. confirmed that the reduced Roseburia abundance could be an independent label for MDD compared to diarrhea-predominant IBS (D-IBS) (Liu et al., 2016). Therefore, the specific microbial profile of nervous disorders should be defined and clarified cautiously in consideration of the differences in the nationalities of the subjects, control baselines, fecal storage, digestive tract problems, and the detection methods used. With FMT, one can partly prove the primary function of gut Roseburia. However, interactions between bacteria and neurons are more complex than are other interactions such as bacteria–epithelium or bacteria–immunity; mechanism studies are lacking. The advancement in the culture techniques of the human microbiota and culturomics has provided a platform to elucidate and uncover new details on the explicit role of Roseburia in neural disorders.

Metabolites derived from R. intestinalis can infiltrate the gut barrier and circulate in the artery and the vein. As such, it is imperative to investigate the effects of R. intestinalis in circulatory diseases ( Table 2 ). A classic role of Roseburia has been proven strongly in the modulation of atherogenesis. In a Swedish study, patients with symptomatic atherosclerosis had less abundant Roseburia than did healthy subjects (Karlsson et al., 2012). Moreover, gut metagenomes are enriched in genes encoding metabolic pathways forming atherosclerotic plaques. Kasahara et al. revealed a negative correlation of Roseburia spp. with the development of atherosclerotic plaques in a mouse model. The study established a murine model colonized with R. intestinalis and fed the transplanted gnotobiotic mice with a high concentration of plant polysaccharides (Kasahara et al., 2018). The results showed that R. intestinalis contributed to the reprogramming of metabolism from glycolysis to fatty acid utilization and the reduction of systemic inflammation. In addition, R. intestinalis inhibited atherosclerotic plaque formation and ameliorated atherosclerosis (Kasahara et al., 2018). A similar phenomenon had been observed in coronary artery disease (CAD) reported by two published large-scale population-based studies by Liu et al., who recruited 161 CAD patients and 40 healthy controls, and Zhu et al., who enrolled 70 CAD patients and 98 healthy controls. These two studies characterized bacterial co-abundance group changes at different disease stages and demonstrated a significant depletion of Roseburia in the CAD group (Liu et al., 2019; Zhu, Q. et al., 2018). In another research group, MGWAS analysis showed a lower abundance of Roseburia spp. in hypertension patients than in healthy controls (Yan et al., 2017). A related animal study also reported reduced Roseburia abundance in a two-kidney-one-clip (2K1C) hypertensive rat model (Qin et al., 2018). Furthermore, Zheng et al. demonstrated a disrupted abundance of bacteria, including Roseburia, in experimental rats from a 4-week heart failure rat model (Zheng et al., 2019). Collectively, these findings suggest a close correlation of the diseases of the circulatory system with Roseburia.

Regarding hematology, studies on disease microbiome are scanty. In one of the investigations, decreased Roseburia abundance was detected in the fecal samples of lymphoblastic leukemia patients (Rajagopala et al., 2016). Another study revealed that mice fed with pectic oligosaccharides had increased intestinal Roseburia spp., and the diet ameliorated leukemia progression in a leukemia mouse model (Bindels et al., 2015). These findings may unravel the role of Roseburia in leukemia. Moreover, studies conducted in Peru and Switzerland reported that iron-deficient anemia patients had a lower fecal Roseburia abundance than did the controls (Dostal et al., 2012; McClorry et al., 2018). These findings provide an insight into the interaction between hematology and microbiology. In this view, we believe that R. intestinalis sustains the stability of the gut ecology and provides persistent indirect benefits in circulation and hematology; the effect is slow, but persistent. It is undeniable that multiomics and single-cell sequencing technologies have greatly improved the breadth and depth of bacteria–circulation research. These new technologies will guide the examination of circulation and the blood effects of germ-free animals after R. intestinalis intervention.

Microbiota-reactive CD4⁺ T cells are essential in intestinal homeostasis because they produce permeability-sustaining cytokines and provide a large pool of T-cell alternatives that repel pathogens (Hegazy et al., 2017). Human immunodeficiency virus (HIV) impacts vast global populations, posing heavy public burdens and life-threatening risks. Evidence shows that HIV attacks the immune system (including the enteric defending barrier) whereby it infects and depletes CD4⁺ T cells. The consequently low CD4⁺ T cells induce gut dysbiosis, systemic inflammation, and clinical complications in chronic HIV patients. Researchers have detected low R. intestinalis abundance in the colonic mucosa of HIV patients compared to that in uninfected patients. In a recent investigation, the abundance of R. intestinalis was found to be inversely correlated with bacterial translocation, immune activation, and vascular inflammation (Dillon et al., 2017). Of note is that data from rectal mucosal microbiota rather than feces indicated depleted Roseburia in HIV patients who did not receive antiretroviral therapy (McHardy et al., 2013). However, the mechanism of dysbiosis induced by low CD4⁺ T cells is complex. In feces of HIV patients, low microbial gene counts (LGCs) but enrichment in R. intestinalis correlated with low nadir CD4⁺ T-cell counts, which could predict gut dysbiosis in HIV (Guillen et al., 2019). In addition, a significantly enriched Roseburia abundance was reported in active tuberculosis (TB) patients, and Roseburia promoted TB pathophysiology by enhancing the anti-inflammatory milieu in the host (Maji et al., 2018). However, a contrary report of a Chinese trial confirmed a decrease in Roseburia abundance in TB patients (Hu et al., 2019). Therefore, further investigation is warranted to address these divergent results.

The cancer-associated microbiome has always been a preference in cancer research. It is worth noting that the microbiota contributes to carcinogenesis and tumor progression in colorectal cancer (CRC), hepatocellular carcinoma, pancreatic tumor, and cervical cancer. Therefore, the microbiota can serve as early diagnostic biomarkers to guide precise cancer treatment. A previous investigation by Liang et al. (2017) reported that R. intestinalis abundance was decreased in CRC patients compared to healthy controls. Notably, the change in R. intestinalis abundance is consistently significant among cancer-associated microbiome studies. In a study by Yu et al. using MGWAS, the abundances of some marked microbes, including R. intestinalis, were decreased in 74 Chinese patients with CRC compared to the controls. These results were consistent with validated data from cohorts in Denmark, France, and Austria (Yu et al., 2017). Similar findings were also documented in independent studies (Wang et al., 2012; Chen et al., 2013). After a careful evaluation of the literature reports on CRC microbiota based on their large size and consistent results, we provide evidence that R. intestinalis may be a definite protective factor and a reliable biomarker in CRC. However, for other cancers (nasopharyngeal carcinoma and cervical cancer), divergent results were found (Jiang et al., 2019; Wang et al., 2019). It is notable that both studies displayed connections between Roseburia abundance and cancer risk, although the results were not related to the beneficial effect of Roseburia. Generally, cancer-associated microbiota is relevant to the cancer microenvironment. R. intestinalis may contribute to the dysfunction of the immune microenvironment and metabolic reprogramming of cancer cells. Recent evidence demonstrated an association of the Clostridiales members of the gut microbiota with a lower tumor burden in mouse models of CRC. Notably, these commensal species, including R. intestinalis, were also significantly reduced in CRC patients compared to healthy controls (Montalban-Arques et al., 2021). A mix of four Clostridiales strains (CC4) in mice prevented and successfully cured CRC as a stand-alone treatment in anti-PD-1 therapy. Also, the bacterial treatment induced a high infiltration of CD8⁺ T cells within the tumor, making them more immunogenic (Montalban-Arques et al., 2021). A single application of R. intestinalis showed higher efficacy than that of CC4 (Montalban-Arques et al., 2021). This section has shown a potential synergy between tumor immunotherapy and microbes. Thus, further cancer-associated microbial studies are warranted to elucidate the role of R. intestinalis in tumor immunotherapy. Although metagenome results could not distinguish the above role, germ-free animals and primary bacterial culture of tumors have great application prospects.

Acute respiratory distress syndrome (ARDS) is an acute lung injury that occurs mostly following an infection, chemical airway burn, or other factors. ARDS is characterized by a disruption of the alveolar epithelial and endothelial barrier, inflammatory effusion, ventilation defect, and severe respiratory failure. Intestinal microbial dysbiosis may aggravate ARDS. A previous study conducted using an acute lung injury rat model (rats were intratracheally instilled with lipopolysaccharides) demonstrated a higher diversity index and a lower number of Roseburia spp. in the gut flora of model rats compared to that of the control group (Li et al., 2014).

In most cases, chronic kidney disease (CKD) is comorbid with metabolic and cardiovascular complications, and most patients can progress into end-stage renal disease. In addition, a deteriorated internal environment frequently accompanies an impaired gut barrier and low-grade inflammation. CKD patients have been shown to harbor shrunken percentages of beneficial microbes, including Roseburia (Xu et al., 2017). In another study, a reduced abundance of Roseburia was reported in the end-stage renal disease group and was negatively correlated with C-reactive protein and cystatin C (Jiang et al., 2017). Some studies have shown a negative correlation of Roseburia with CKD severity at different stages of the disease (Wu, I. W. et al., 2020), and related studies continue to emerge. This review has repeatedly confirmed the beneficial role of Roseburia in different diseases. However, the precise role of Roseburia spp. could hardly be defined because dysbiosis is expected in such diseases. Nevertheless, we are more convinced that Roseburia is a potential probiotic.

Many clinical studies of human cohorts using established disease models have documented the protective role of Roseburia spp., especially R. intestinalis. Nearly all the data demonstrate a probiotic role of R. intestinalis in preventing infection and in relieving and reversing the pathological process. Notably, R. intestinalis has displayed a beneficial role in different modes, such as butyrate, supernatant, flagellin, and organism effect. In combination with other emerging evidence, findings from our research group have revealed the effect of R. intestinalis on Tregs, ILC3, Th17, and macrophages and the stimulation of anti-inflammatory cytokines (IL-22, IL-17, IFNγ, TSLP, and OSM). There is evidence that different technologies have been applied to modulate R. intestinalis-associated disease treatment ( Figure 3 ), and the significance of FMT as a microbial treatment choice in diseases is well highlighted. For example, Clostridium difficile colitis is associated with microbiota dysbiosis caused by the overuse of antibiotics. FMT, as standard therapy, reverses microbiota dysbiosis and maintains the natural microbiota. FMT also demonstrates favorable potential in managing chronic inflammatory disorders, including UC. A randomized, double-blinded controlled trial, for instance, demonstrated that the application of FMT to manage active UC patients improved the microbial diversity and altered the bacterial taxa. Furthermore, patients in the remission group displayed more abundant Roseburia spp. and higher SCFA levels than those who experienced no remission after FMT (Paramsothy et al., 2019). Another investigation proposed that Roseburia species could be the prominent candidates for the probiotic treatment of patients with IBD based on the consistent results in the experimental center (Kellermayer, 2019). In our previous study (Yang et al., 2020), CD patients who received FMT showed significant improvement in the number of operational taxonomic units (OTUs) and Shannon diversity index than did donors, 2 weeks after FMT, which included R. intestinalis. Collectively, R. intestinalis might play a beneficial role in the recovery of the gut microenvironment and the improvement of disease pathophysiology through FMT.

It is well known that the butyrate produced by R. intestinalis is a prebiotic. Researchers have attempted to directly or indirectly administer butyrate or butyrate “carriers” such as tributyrin (Wächtershäuser and Stein, 2000; Tuleu et al., 2001; McNabney and Henagan, 2017). For effective absorption, rectal butyrate enema had been previously introduced in UC treatment (Hove et al., 1995). Similarly, our research group revealed the therapeutic effect of R. intestinalis by suspension gavage in mice. In this view, we strongly suggest a need to develop viable probiotics based on R. intestinalis in medicine. Whole-grain diets with abundant fiber can also be fermented using R. intestinalis. Of note is that other special prebiotic supplements, such as acetate, xylan, β-mannans, and protein hREG3α, alter the abundance of R. intestinalis and butyrate production and promote niche superiority. As such, the application of R. intestinalis can benefit from advancement in the development of materials. Recently, in our laboratory, we developed a magnetic iron oxide nanoparticle (MION) internalized R. intestinalis, and the magnetic field can be directed both in vitro and in vivo (Xiao et al., 2019). Additionally, a careful investigation of the viability and cytotoxicity of MION internalized R. intestinalis and a custom-made magnetic guide facility were conducted in vitro. The results demonstrated good orienteering and the anti-inflammatory effect of MIONs in the TNBS-induced colitis mouse model (Xiao et al., 2019).

More findings from our laboratory indicated that the flagellin from R. intestinalis displayed a favorable anti-inflammatory effect via intraperitoneal injection (Quan et al., 2018; Wu, X. et al., 2020). These results strongly suggest that purified flagellin may be a safe and effective therapy for intestinal immune modulation. Furthermore, some tryptophan metabolites, including indoles, may be a new choice targeting R. intestinalis-associated mechanisms, for example, IL-22 production and ILC3 activation by the AhR. Therefore, further well-designed studies and credible clinical trials should be conducted to clarify the beneficial effects of R. intestinalis.

Regarding the safety of R. intestinalis, our laboratory is evaluating its risk in mouse symptoms, circulating system, and organs systemically. Further data will estimate its safety. Evidence should be accumulated in its safety and proper uptake dose. As a probiotic candidate, preclinical evaluation and clinical trials are urgently needed to prove its therapeutic potential in diseases.

In 2014, the International Scientific Association for Probiotics and Prebiotics consensus statement updated the scope and appropriate use of the term probiotic. The reinforced concept defines probiotics as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. The expert consensus listed several probiotic candidates, including A. muciniphila, F. prausnitzii, Roseburia spp., and Eubacterium hallii (Hill et al., 2014). It is expected that therapeutic approaches targeting R. intestinalis will significantly improve specific human pathogenic status. Notably, inflammatory bowel disease exhibits significant changes in the abundance of R. intestinalis and benefits the most from its modulations. Recent breakthroughs also suggest the probiotic role of R. intestinalis, which has a widespread effect in preventing intestinal inflammation and maintaining energy homeostasis based on its metabolites, and noumenon. R. intestinalis could impact the functions of immune cells and the release of cytokines through its metabolites, butyrate and flagellin, and other unknown supernatant components. Advancements in primary culture technology, culture omics, single-cell sequencing, and metabonomics technology are expected to help researchers in elucidating the role of Roseburia spp. in order to lay a solid foundation in the maintenance of human health and treatment strategies for diseases in the future. Based on the available evidence, focused, well-designed randomized controlled trials, and future high-quality systematic reviews and meta-analyses should be urgently conducted to uncover the probiotic role of R. intestinalis. In conclusion, as a significant butyrate producer, R. intestinalis, which belongs to the Roseburia species, has great application prospects in the development of novel probiotics. It is possible that R. intestinalis can exert a specific and a significant therapeutic influence in different diseases associated with microbial dysbiosis.

KN reviewed all the literature and wrote the manuscript. KM, WL, ZS, ZY, TT, and XM undertook most of the group’s research work and published their findings. They also discussed each part of the manuscript and helped form our viewpoints. YY funded us and edit the manuscript. XW conducted the research group including above authors and edited the manuscript. All authors contributed to the article and approved the submitted version.

This project was supported by the National Natural Science Foundation of China (NSFC nos. 81970494 and 81800500) 81970494 was grant to XW and 81800500 to YY.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.