An Overview of Small Intestinal Bacterial Overgrowth and Gut Microbiota in Patients with Rosacea

Abstract

Rosacea is a chronic skin condition characterized by persistent inflammation, manifesting primarily on the face and causing redness, papules, pustules, and phymatous changes. The etiology of rosacea is multifactorial, with immune system factors playing a crucial role in its pathogenesis. The scientific literature contains an increasing number of studies that suggest a correlation between rosacea and the gut microbiota. Small intestinal bacterial overgrowth (SIBO) is defined as an excessive proliferation of potentially pathogenic bacteria within the small intestine of the gastrointestinal system. Multiple factors have been posited to explain the pathogenesis of rosacea, and the presence of SIBO has been identified as a potential factor in its occurrence. A decrease in the Lactobacillus genus, Prevotella copri, Lachnospiraceae, and Faecalibacterium within the gut microbiota may initiate inflammation related to rosacea. These bacterial species are crucial for regulating the intestinal mucosa. The findings indicate that there is an increase in Bacteriodes, Acidaminococcus, Megasphaera, and Ruminococcus in the gut microbiome of patients with rosacea. Probiotics can be advantageous for managing the intestinal microbiome, while Rifaximin treatment has shown efficacy in addressing inflammatory rosacea lesions associated with SIBO. The present review has been undertaken with the objective of enhancing our comprehension of SIBO in rosacea. The emphasis has been placed on the pathogenetic mechanisms and the shift in the gut microbiota that will lead to understanding probiotic benefits and therapy options in rosacea patients.

1. Introduction

Rosacea, a prevalent dermatological condition, is estimated to influence between 1% and 20% of the global population [1]. The clinical characteristics of rosacea are typically characterized by recurring flare-ups of flushing, persistent redness, telangiectasia, papulo-pustules, or phymatous changes. Additionally, there is a multiphasic phenotype spectrum of disease, accompanied by burning, pain, or migraine-like symptoms [2]. The clinical classification of rosacea encompasses the following subtypes: erythematotelangiectatic rosacea (ETR), papulopustular rosacea (PPR), phymatous rosacea, and ocular rosacea. A recent clinical subtype known as neurogenic rosacea has also been documented [3]. The etiology of rosacea is complex and multifactorial, with potential contributors including microbiological, neurovascular, immune, ultraviolet radiation, genetic, dietary, and psychological stress factors. Collectively, these factors may contribute to the inflammatory process [4]. Due to the multifactorial etiology of rosacea, there is considerable heterogeneity among the results of therapeutic interventions targeting rosacea. The primary approach to managing rosacea involves patient education, the establishment of a skin care routine, treatment with topical and oral medications to control flare-ups, and the use of lasers or light-based therapies. It is imperative that treatment should be adapted to the individual’s specific needs, and a combination of various therapeutic modalities is frequently necessary to address the diverse manifestations of rosacea [5].

The significance of the skin-gut axis is becoming increasingly evident with the advancement of our understanding of the underlying pathophysiological mechanisms [6]. As an inflammatory disease, rosacea has been shown to be associated with small intestinal bacterial overgrowth (SIBO), a condition involving an imbalance in the composition of the gut microbiota [7]. Although the precise mechanisms of the gut-skin axis have yet to be fully elucidated, mounting evidence indicates that the probiotic intervention may confer benefits in the context of inflammatory cutaneous conditions [6].

This narrative review explores the correlation between rosacea and SIBO, offering a theoretical framework for understanding how SIBO could have a potential effect on the immune mechanism affecting rosacea pathogenesis.

2. Materials and Methods

A literature search was conducted on the PubMed, Web of Science, and Scopus databases using keywords including “rosacea”, “gut”, “intestine”, “microbiome”, “microbiota”, and “dysbiosis”, up to December 2025. A meticulous examination of the extant studies that assessed alterations in the intestinal microbiota in rosacea patients was undertaken. The inclusion criteria for this study were human case–control studies exploring the relationship between gut microbiota and rosacea, employing methods for quantifying gut microbiota via sequencing and analysis, and articles written in English. The exclusion criteria encompassed review articles, meeting abstracts, case reports, and experimental studies employing animal models.

3. The Relationship Between the Skin and the Intestinal Microbiome

The skin and intestine exhibit numerous similarities in their structural and functional characteristics. They play pivotal roles as immunological barriers, thereby establishing the environment for physiological microflora [8]. These organs possess a well-developed vascular infrastructure, diverse microbial biota, and serve as pivotal interfaces that facilitate communication between the inner human body and the outer environment [9]. The relationship between the two organs has been documented in the context of various conditions, including inflammatory bowel diseases, gastrointestinal malignancies, and Peutz–Jeghers syndrome [8]. Furthermore, a number of dermatological disorders, including acne, atopic dermatitis, psoriasis, and rosacea, have been associated with intestinal dysbiosis [10].

The skin and intestines serve as neuro-immuno-endocrine organs, facilitating crucial interactions between the nervous, immune, and endocrine systems [11]. For instance, psychological stress has been demonstrated to play a crucial role in the exacerbation and onset of several skin disorders [12]. In addition, the intestinal microbiota can produce neurotransmitters in response to stress and other external triggers. These neurotransmitters have the capacity to modify skin functioning via neural pathways, including norepinephrine, serotonin, and acetylcholine. Moreover, these neurotransmitters may trigger the release of neuropeptides from proximate enteroendocrine cells [13].

The intestine is dominated by anaerobic organisms, including members of phyla Bacteriodetes (Bact.) and Firmicutes (Firm.). The composition of the intestinal microbiota is shaped by various factors, including anatomical location, niche, and extrinsic influences, as well as nutritional regimens [14]. Small intestine microbiota exhibits greater variability than that of the large intestine, with significant shifts in ileal microbial composition occurring within a 24 h period [15]. The intestinal microbiota may exert an influence on skin homeostasis by modulating systemic immunity. Microorganisms are capable of impacting the intestinal barrier integrity and skin homeostasis exerted through the process of cross-talk with mucosal immunity elements and signaling pathways that coordinate the differentiation of epidermal metabolites onto the skin. This phenomenon serves to illustrate the impact of the gut microbiota on the physiology of the skin, the immune system, and the progression of pathology [16]. In addition, the metabolites p-cresol and phenol, produced by Clostridioidium difficile (C. difficile), which have been identified as biomarkers for gastrointestinal microbiota imbalances, have the ability to enter the blood circulation, subsequently accumulating on the skin’s surface, resulting in a decrease in skin hydration, impairment of skin barrier function, epidermal differentiation, and keratinization [17,18].

The physiological characteristics of the gut epithelium can be modified by bacterial products and dietary components, potentially leading to alterations in the secretory processes of the epithelium. These changes may result in the systemic circulation of these secretory products and subsequent contact with the skin. Additionally, neurotransmitters, hormones, and other biologically active compounds, including short-chain fatty acids (SCFAs) originating from the gastrointestinal tract, have the capacity to interact with receptors present within the epidermis, thereby inducing direct alterations in skin physiology or the composition of its resident microbiota [9]. Therefore, the existence of a correlation between the gut microbiota and skin homeostasis is plausible, with the potential for the microbiome to exert influence on organs external to the gastrointestinal tract [16].

4. Small Intestinal Bacterial Overgrowth

The gut microbiota performs a pivotal and advantageous function in maintaining the normal physiological mechanisms of the human organism. Additionally, the microbiota provides protective benefits against pathogens through several mechanisms, including direct barrier functions, the secretion of antimicrobial peptides, and the stimulation of immune signaling pathways. Dysregulation of the microbiome, whether due to shifts in its location or composition, can have detrimental consequences on overall health [19,20]. Gut commensal bacteria have the capacity to influence the immune system of the host in a multifaceted manner, thereby fostering immune tolerance to dietary and environmental antigens and offering defense against incursions by foreign pathogens [7,21]. A shift in microbial composition or abundance, referred to as gut dysbiosis, has the potential to disrupt the body’s normal homeostasis [20]. It is possible for dysbiosis to cause a weakened intestinal mucosal layer and dysfunctional epithelial tight junctions. This can lead to compromised intestinal barrier integrity and facilitate the migration of noxious bacterial metabolites and compounds. In addition, bacterial components capable of triggering the immune response within the gastrointestinal tract can be transported to systemic circulation [22]. Alterations in the structure of the gut microbiota may result in immunological imbalances in the organ systems external to the gastrointestinal system because almost 70% of lymphocytes are present in the lymphoid tissue of the gut [23].

The condition known as dysbiosis has been linked to a number of intestinal and extraintestinal pathologies, including SIBO [20]. SIBO is a medical phenomenon defined as the existence of elevated bacterial loads in the small intestine, resulting in gastrointestinal manifestations. While the predominant localization of the gut microbiota is in the large and distal small intestine, there is a possibility of their infiltration into the mid and proximal small intestine, which can result in the development of SIBO [19]. The definitive prevalence in the overall demographic remains indeterminate; though, extant studies suggest a range of 2–22%, classifying it as a reasonably prevalent ailment. In addition, there is an observable rise in the prevalence of the condition with increasing age, particularly among populations afflicted with comorbidities [24].

The predominant etiological factor of SIBO is the presence of dysmotility along the gastrointestinal system. The migrating motor complex is a contributing factor to the elimination of fecal matter within the gastrointestinal canal. It has been observed in a range of anatomical intestinal abnormalities or conditions, including intestinal obstructions, diabetic gastroparesis, diverticulosis, and scleroderma [25]. The standard diagnostic approach for SIBO involves the administration of a lactulose or glucose breath test, a non-invasive and cost-effective method [19]. Recent research has demonstrated that the Firm./Bact. (F/B) ratio in the gut can function as a biomarker, indicating inflammation. An elevated F/B ratio is commonly associated with dysbiosis and enhanced inflammation [26,27].

SIBO eradication can promote nutritional wellness and symptomatic control in patients; however, recurrences may occur, contingent upon the presence of intestinal motility dysfunction. Treatment modalities for SIBO encompass the administration of antibiotics, the use of probiotics, dietary modifications, prokinetic agents, and supportive care [28]. Antibiotic usage is imperative for the treatment of SIBO [29]. The empirical treatment of SIBO often involves the administration of metronidazole, ciprofloxacin, tetracycline, amoxicillin-clavulanate, neomycin, or rifaximin, owing to the challenges associated with adequate sample collection [30]. However, the utilization of broad-spectrum antibiotics such as vancomycin and amoxicillin can impede the proliferation of beneficial Firm., thereby establishing a favorable environment for the colonization of C. difficile, which can be characterized as dysbiosis [29]. Although there is documented heterogeneity across studies and the absence of consensus on dosing and treatment duration, rifaximin has demonstrated efficacy in addressing SIBO [31]. Furthermore, probiotics have been suggested to be efficacious in decreasing the bacterial burden in SIBO patients and mitigating their symptoms via modifying gut microbiota, maintaining the intestinal epithelium’s integrity, enhancing anti-inflammatory cytokines and growth factors, producing short-chain and branched-chain fatty acids, and engaging with the brain–gut axis by modulating endocrine and neurological processes [32,33]. In addition to these established therapeutic modalities, the utilization of oral antimicrobial botanical supplements in the management of SIBO is gaining traction as a complementary approach [34].

5. Pathogenesis of Rosacea and Small Intestinal Bacterial Overgrowth

In rosacea etiology, both innate and adaptive immunity have been demonstrated to exert influence [4]. Toll-like receptor-2 (TLR-2) is a pattern recognition receptor that can identify molecular patterns present in microbial compounds, thereby activating the immune system as a defense mechanism [35]. Elevated levels of TLR-2, Kallikrein-5 (KLK-5), cathelicidin, and matrix metalloproteinases (MMPs) have been observed in patients with rosacea [36]. Stimulation of TLR-2 results in the activation of the nuclear factor-kappa B (NF-κB) pathway, which leads to the synthesis of chemokines, cytokines, and antimicrobial peptides (AMPs) in the proinflammatory cathelicidin pathway [37]. Moreover, stimulation of TLR-2 results in the production of active human cathelicidin-derived antimicrobial peptide (LL-37) via triggering KLK-5, which is a serine protease responsible for cleaving cathelicidin antimicrobial peptide (CAMP) and producing active peptides [38,39]. KLK-5 is expressed in an inactive form that is subsequently converted to an active form through cleavage performed by MMPs, especially MMP-9 [40].

The increased levels of CAMP and KLK-5 can augment the levels of the shorter LL-37 fragment forms in rosacea skin [41,42]. These shorter LL-37 fragments have been demonstrated to induce symptoms consistent with rosacea, including erythema, vasodilatation, flushing, and telangiectasia in mice [41]. Furthermore, the activation of the nucleotide-binding oligomerization domain like receptors family, pyrin domain-containing 3 (NLRP3) inflammasome, has been determined to have an important effect on LL-37-induced skin inflammation and rosacea pathogenesis [43]. The NLRP3 inflammasome has been defined as a multiprotein complex that is responsible for the stimulation of caspase-1 and interleukin (IL)-1β. This leads to the activation of the IL-1 receptor in multiple cells and the infiltration of neutrophils [44].

Increased levels of LL-37 have been shown to induce the release of pro-inflammatory cytokines by neutrophils, including IL-8, IL-1β, and tumor necrosis factor (TNF)-α. Furthermore, LL-37 has been observed to stimulate the synthesis of vascular endothelial growth factor (VEGF) and activate the epidermal growth factor receptor signaling pathway [38].

In rosacea, T-cell immune responses are initiated through the actions of T helper (Th)1 and Th17 cells, leading to elevated levels of interferon-γ (IFN-γ) and IL-17 [45]. Th17 cells have been observed to produce IL-17, which may play a role in the effects on LL-37 through the expression of atypical forms that are characteristic of rosacea. IL-17 has been shown to induce angiogenesis through the VEGF pathway and to regulate the expression of LL-37 [46,47].

TLR activation is imperative for specific antigen-specific antibody responses in B cells, and TLR agonists have been shown to promote the proliferation of plasma cells from B cells [48]. Cleaved fragments of LL-37 robust B cell immune response accompanied by increased expression of Th17 and Th22 cytokines [49]. All these processes could be explained as contributing factors to the chronic inflammatory process and enhanced angiogenic growth that are characteristic of rosacea.

Pathogen-associated molecular patterns (PAMPs) are defined as biological stimulants that elicit a response in TLRs, including TLR-2 [50]. SCFAs have been demonstrated to facilitate the maintenance of intestinal barrier integrity. These acids are produced by healthy gut microbiota from complex polysaccharides [51]. The significance of SCFAs extends beyond their role in diminishing intestinal permeability, as they also modulate skin barrier integrity by inducing keratinocyte metabolism and differentiation [52]. Butyrate is an SCFA and demonstrates a robust anti-inflammatory effect by suppressing immune reactions via inhibiting cytokine production by inflammatory cells [53]. The presence of elevated PAMPs in the circulation system, along with a decline in butyrate of bacterial origin, which is a protective factor for the intestinal barrier, might suggest an increased responsiveness of B-cells and impairment in the differentiation of T-cells [54]. Despite the absence of evidence demonstrating the full complement of innate and adaptive pathways in the existing studies, the hypothesis that SIBO may induce analogous pathways is a plausible one. This is due to the fact that dysbiotic bacteria instigate similar pathways in both the gastrointestinal tract and the skin (Figure 1).

6. Clinical Correlation Between Rosacea and Small Intestinal Bacterial Overgrowth

Research has demonstrated the efficacy of SIBO treatment in achieving remission of rosacea, as evidenced by studies conducted on the subject. In a study, findings indicated a higher risk of SIBO in patients diagnosed with rosacea compared to the control group. This study revealed that 32 (%51) out of 63 patients diagnosed with rosacea exhibited signs of SIBO (relative risk: 2.1; 95% confidence interval: 1.7–15.1). Additionally, 28 patients receiving rifaximin treatment reported a clearance or marked improvement in their rosacea symptoms or findings, with a 46% response rate [55]. Another study, which was prospective and randomized controlled, revealed that 52 of 113 rosacea patients exhibited signs of SIBO. In this study, patients diagnosed with rosacea and SIBO were administered rifaximin (400 mg every eight hours for a duration of ten days). Rosacea exhibited a positive response to the treatment, with 78% of patients demonstrating clearance of symptoms or a substantial improvement in their conditions. In contrast, the placebo group exhibited no change or deterioration in symptoms over the same duration. The efficacy of the treatment was sustained, as evidenced by the reduction in rosacea symptoms in 96% of patients at the 9-month follow-up. Notably, the majority of patients no longer had SIBO [56]. A cohort study yielded no statistically significant correlation between SIBO in patients diagnosed with rosacea and those in the control group (hazard ratio: 0.71; 95%confidence interval: 0.18–1.86) [57]. A three-year observational study was conducted to investigate the role of SIBO in the pathophysiology of rosacea. The study’s findings indicated that treatment with rifaximin for SIBO resulted in clinical improvement, with remission being achieved in all patients. This response was observed to be consistent over the course of the follow-up phase, with the predominant proportion of patients sustaining this state of remission. In addition, a notably elevated prevalence of SIBO has been documented in patients afflicted with PPR in comparison to those with ETR [58].

7. The Intestinal Microbiota in Rosacea Patients

The studies presented herein demonstrate alterations in the intestinal microbiota that may be particularly relevant to patients diagnosed with rosacea (

Table 1. Intestinal microbiota of patients with rosacea.

Authors and Year	Study Design	Increased Levels of Intestinal Microbiota	Decreased Levels of Intestinal Microbiota	Results
Moreno-Arrones et al. [59] 2021	15 PPR patients 12 (80%) females 15 controls 5 (33.3%) females LEfSe analysis	Syntrophomonadaceae Anaerovorax genus Bacteroidales sp. Tyzzerella sp. Lachnospiraceae, Akkermansia muciniphila Parabacteroides distasonis	Prevotella copri	Possible intestinal dysbiosis
Chen et al. [60] 2021	11 patients 4 ETR 36.3% 7 PPR 63.7% 90.9% female 110 controls 90.9% female LEfSe analysis	Rhabdochlamydia CF231 Bifidobacterium Sarcina Ruminococcus	Lactobacillus Megasphaera Acidaminococcus Haemophilus Roseburia Clostridium Citrobacter	Possible intestinal dysbiosis
Nam et al. [61] 2018	12 female patients ETR 50%, PPR 17% 251 female controls MetagenomeSeq	Acidaminococcus Megasphaera Lactobacillales	Peptococcaceae Methanobrevibacter Slackia Coprobacillus Citrobacter Desulfovibrio	Possible intestinal dysbiosis
Guertler et al. [62] 2024	54 patients 39 females 15 males 50 controls MiSeq 16S rRNA sequencing	Oscillobacter sp. Flavonifractorplauti Ruminococccaceae UBA1819	Faecalibacterium prausnitzii Lachnoospiraceae ND 3007 Ruminococcaceae	Possible intestinal dysbiosis

PPR: papulopustular rosacea; ETR: erythematotelengiectatic rosacea; LEfSe: linear discriminant analysis effect size.

).

A study was conducted in which the gut microbiome of 15 patients diagnosed with PPR was compared with that of 15 healthy controls. Twelve patients diagnosed with rosacea were female and had a mean age of 36 years; 13 subjects who served as controls were also female and had an average age of 39 years. The results obtained via canonical correspondence analysis were found to be significantly different between the patients and controls. The implementation of a linear discriminant effect size (LEfSe) analysis has led to the identification of an increase in the Syntrophomonadaceae family, Anaerovorax genus, Bacteroidales species (sp.), Tyzzerella sp., Lachnospiraceae (Lach.) family, Akkermansia muciniphila and Parabacteroides distasonis. It was determined that these bacteria were characterized as compositional elements indicative of PPR patients. The LEfSe analysis indicated a decline in the prevalence of Prevotella copri. The study delineates the intestinal microbiological profile of patients afflicted with inflammatory rosacea, thereby substantiating the notion of intestinal dysbiosis [59].

In a research study, the intestinal microbiota of 11 rosacea patients was compared with the microbiota of 110 age- and sex-matched individuals who were considered to be healthy. More than 90% of participants in both groups were females. In the rosacea group, 90.9% were female, with a mean age of 49.9 ± 11.3 years. Furthermore, 4 of the patients (36.3%) had ETR, and 7 of them (63.7%) had PPR. A decline in abundance, though not in the uniqueness of bacterial diversity, was demonstrated in rosacea patients. The incorporation of additional variables, including alcohol consumption, tea or yogurt intake, tobacco use, exercise habits, vegetarian diet, and rosacea subtype, revealed no significant impact on the structure of the gut microbiota, as indicated by principal coordinate analysis (PCoA). A comparative analysis of the gut microbiota revealed that both groups exhibited a predominance of Bact., Firm., and Proteobacteria. Nevertheless, a notable distinction was identified in the rosacea subjects, who exhibited an increased prevalence of Bacteroides and Fusobacterium, and a reduced prevalence of Prevotella and Sutterella, in contrast to the control group. The LEfSe analysis revealed substantial changes in the composition of the intestinal microbiome in patients with rosacea, characterized by increased abundance of Rhabdochlamydia, Bifidobacterium, Sarcina, and Ruminococcus (Rumin.), as well as a reduction in the levels of Lactobacillus (Lb.), Megasphaera (Mega.), Acidaminococcus (Acid.), Haemophilus, Roseburia, Clostridium, and Citrobacter. Rosacea patients exhibit distinctive characteristics in their fecal microbiota, which may be associated with sulphur metabolism, cobalamin, and carbohydrate transport [60].

In a separate study, the relationship between the gut microbiota of 12 female rosacea patients and 251 female healthy controls was evaluated. The patient population exhibited a spectrum of subtypes, including 50% ETR, 17% PPR, and other subtypes. The study revealed no statistically significant disparities in diversity metrics between subjects with rosacea and those without rosacea, suggesting that the presence of this skin condition does not significantly impact α- and β-biodiversity levels. Additionally, the study indicated that patients with rosacea exhibited distinct compositions of enteral microbiota, yet these compositions were comparable in abundance to those of the control group. Nevertheless, substantial disparities were identified at the level of genera. Using metagenomeSeq for comparison of differentials in the subjects, there was a significant abundance of Acid. and Mega., in contrast to the paucity of the Peptococcaceae family, and Methanobrevibacter were observed in the patients in comparison with the control group. Moreover, while the levels of Lactobacillales are elevated in patients with rosacea, those of Slackia, Coprobacillus, Citrobacter, and Desulfovibrio are diminished in comparison to the control group [61].

A recent study examined the disparities in fecal microbial profiles, as analyzed with MiSeq 16S rRNA sequencing, among patients diagnosed with 54 cases of rosacea compared to 50 healthy controls. A decrease in microbial richness and diversity was identified in patients with rosacea in comparison with the control group. In rosacea, a significant decrease was observed in the levels of Faecalibacterium prausnitzii (F. prausnitzii), Lach. ND 3007 group sp., and Ruminococcaceae (Rum.). Conversely, Oscillobacter sp., Flavonifractor plautii, and Rum. UBA 1819 exhibited a marked increase in their abundance in cases of rosacea when compared to the control group. The present study found no statistically significant associations between the degree of rosacea severity or the existence of gastrointestinal manifestations and intestinal microbiome features [62].

Another study was conducted to ascertain the correlation between the gut microbiome and rosacea. The study was not designed to include a controlled group, nor was the variation in the intestinal microbiota species examined. In this study, a two-sample Mendelian randomization (MR) design was employed, and data derived from the Genome-Wide Association Study focused on gut microbiota and the FinnGen biobank for rosacea. The study identified and analyzed 2078 single-nucleotide polymorphisms (SNPs) that are linked to the gut microbiota. The study has indicated that two bacterial genera, Actinomyces and Butyrivibrio may play a pivotal role in preventing the development of rosacea. The results of the MR analysis indicated the absence of pleiotropy, with a uniform distribution exhibited across a selected set of SNPs. Tests of directionality indicated a substantial causative pathway from gut microbiota to rosacea [63].

8. Probiotics and Rosacea

According to the International Scientific Association for Probiotics and Prebiotics, the term “probiotics” refers to “live microorganisms that, when administered in sufficient amounts, offer a health benefit to the host.” [64]. It has been demonstrated that the ingestion of probiotics can alleviate inflammatory responses in the intestinal tract by stimulating innate immune responses within the gut. The proposed mechanistic structure for probiotics entails a multifaceted process, including the enhancement of epithelial barrier functionality, the augmentation of TNF-alpha production by epithelial cells, and the stimulation of the NF-κB pathway [65]. A multitude of studies and reports in the literature exhibited the efficacy of probiotics in the treatment of rosacea and related skin disorders by virtue of their ability to inhibit inflammation and restore the skin barrier. A case study of scalp rosacea revealed that the patient underwent treatment with an 8-week course of doxycycline (40 mg once daily) and probiotic therapy (Bifidobacterium breve BR03, Lb. salivarius LS01, 1 × 10⁹ UFC/dose). Following a period of eight weeks, the patient returned to the department, exhibiting a substantial enhancement in both cutaneous and ocular manifestations [66]. The therapeutic intervention with Escherichia coli (E. coli) Nissle 1917 was found to have a significant effect on patients with acne, papular-pustular rosacea, and seborrheic dermatitis, with improvements or complete recovery as compared to 56% of patients in the control group (p < 0.01). This study demonstrated a substantial elevation in serum IgA levels, which returned to normal values. Concurrently, a suppression of the proinflammatory cytokine IL-8 was observed. This finding was attributed to the clinical improvement observed in these patients (p < 0.01) [67]. Another study involved 60 patients diagnosed with rosacea, who were randomly divided into three groups: probiotic, placebo, and control. The results demonstrated that the administration of probiotics resulted in improvements to facial skin conditions, a reduction in inflammation, and a decrease in facial skin microbiota diversity, concurrent with an enhancement of gut microbiota heterogeneity [68]. Given the documented increase in the prevalence of SIBO in patients with PPR compared to those with ETR [56]. PPR can benefit from the anti-inflammatory properties of probiotics, contingent upon the inflammatory etiology of the disease.

The potential efficacy of probiotics in managing rosacea via oral administration, such as E. coli Nissle, a combination of Bifidobacterium strains, and a combination of Bifidobacterium with Lb. was investigated. These treatments were administered in conjunction with conventional rosacea therapeutic regimens. The clinical improvements observed included notable symptomatic alleviation and a decrease in recurrences for a period of up to six months following the commencement of therapy [69].

In a study employing a mouse model of rosacea, the effectiveness of probiotics in addressing rosacea was evaluated by conducting an LL-37-induced model of the skin condition. The mixture of Lacticaseibacillus (Lacti.) salivarius 23-006 and Lacti. paracasei 23-008 exhibited the utmost significance in its effect, thereby alleviating dermatological manifestations, reducing the presence of inflammatory cellular infiltrates, and decreasing the levels of inflammatory mediators in mice. The concomitant administration of these two strains resulted in a reduction in the synthesis of cathelicidin LL-37 and rosacea-associated factors. This effect was achieved by inhibiting the TLR2/MyD88/NF-κB pathway [70], which is responsible for the synthesis of chemokines and AMPs, as well as cytokines, within the proinflammatory cathelicidin cascade [37].

It is hypothesized that when administered directly to the skin, there is the potential for probiotics may exert a beneficial effect on the skin barrier via crucial biological processes associated with barrier function and skin reactivity by means of immune modulatory mechanisms. In a study, Lacti. paracasei CNCM-I 2116 (ST11) has been demonstrated to regulate reactive skin-associated inflammatory responses by reversing vasodilation, edema, mast cell degradation, and TNF-alpha release triggered by substance P, in comparison to the control group [71]. Another study indicated that Bifidobacterium longum strains have a pro-differentiating and pro-regenerating effect on primary human epidermal keratinocytes [72]. On the other hand, the colonization of topical probiotics in the skin may be impracticable due to environmental factors. Nevertheless, the combination of oral and topical probiotics could contribute to the development of personalized treatment regimens for skin disorders [65]. The present findings provide a theoretical base for managing rosacea, thus offering a novel and potentially efficacious approach for clinical applications or probiotics.

9. Discussion

The findings of the studies in the literature hypothesized that there is a change in the gut microbiome in patients with rosacea, which is related to the inflammatory process of the skin. Chen et al. revealed a decline in the prevalence of Lb. genera in the fecal microbial profile of patients diagnosed with rosacea [60], which may potentially contribute to the development of dysbiosis in these patients. Lb. is known to play a vital role in defending against pathogenic microorganisms, modulating inflammation, managing gut flora, and preventing bacterial infections [73].

Morena et al.’s study demonstrated a decline in the levels of Prevotella copri [59], which has been shown to have a protective effect on the mucosal barrier and to reduce the likelihood of inflammation by producing SCFAs through the process of fiber metabolism [74]. In addition, Guertler et al.’s study revealed a decline in the abundance of Lach. and F. prausnitzii [62]. These bacteria have been identified as key contributors to the production of butyrate, which has been shown to possess anti-inflammatory properties [75]. A decrease in Peptonococcaceae bacteria in rosacea patients was revealed in Nam et al.’s study, which suggests the potential for these bacteria to serve as butyrate producers. This decline in these bacteria may be associated with an inflammatory response [61,76].

The findings indicate that there is an increase in Bacteriodes [59], Acid., Mega. [61] and Rumin. [62] in the intestinal microbiota of rosacea patients and it is possible that these results may serve as a rationale for the development of inflammation in these patients. Accordingly, the substantial presence of the genera Bacteroides, Rumin., Acid., and Mega. in the gut microbiome has been identified as a significant factor linked to the various disease-related groups [75]. The present findings propose a hypothesis that suggests a potential association between elevated levels of intestinal dysbiosis and inflammation in patients with rosacea. The impact of gut microbiota on the skin prompts the recommendation of rifaximin and probiotics as a means of promoting beneficial bacteria within the gastrointestinal tract. However, further research is necessary to elucidate the causal relationship between the gut microbiome and rosacea.

The present review has limitations due to the restricted number of studies that have been conducted on the microbial flora of patients with rosacea. Moreover, the studies were characterized by their limited sample size, a factor that undermined their efficacy. The study’s strength lies in its presentation of an outline for the clinical and pathogenetic association between rosacea and SIBO.

10. Conclusions

Rosacea is a multifactorial and complex condition; as such, therapeutic options should address the underlying etiological reasons for its development. The identification and management of an underlying SIBO in patients diagnosed with rosacea may offer a therapeutic avenue for reducing the frequency of rosacea flare-ups. As our understanding of the microbiological pathogenetic mechanisms underpinning rosacea progresses, effective management strategies directed at inflammation will be developed. Therefore, the necessity for longitudinal and interventional studies is imperative to promote research advancement and facilitate the development of targeted therapeutic interventions for rosacea.