Microbiota-nutrition sequential therapy for refractory radiation proctitis: A case report

Abstract

BACKGROUND

Gut dysbiosis is closely associated with radiation-induced intestinal injury. This study aimed to preliminarily assess the efficacy and safety of fecal microbiota transplantation (FMT) combined with immunomodulatory enteral nutrition (IEN) for the treatment of refractory radiation proctitis.

CASE SUMMARY

A 49-year-old woman with prior cervical cancer treated by hysterectomy 4 years earlier presented with left inguinal lymphadenopathy. Following radiotherapy, the patient experienced lower abdominal pain, diarrhea, and hematochezia, diagnosed as radiation enteritis. The patient underwent two FMT with adjunctive IEN support. Symptoms alleviated from Common Terminology Criteria for Adverse Events grade 3 proctitis to grade 2 after the first FMT, and further to grade 1 after the second. Nutritional and immune indices improved obviously: Body mass index (20.28 kg/m²→24.34 kg/m²), total protein (63.7 g/L→73.7 g/L), albumin (35.8 g/L→40 g/L), lymphocyte count (0.94× 10⁹/L→1.37 × 10⁹/L) and lymphocyte percentage (18.2%→34.8%) rose, while procalcitonin dropped from 0.07 ng/mL to 0.03 ng/mL. The Vienna Rectoscopy Score declined from 25 to 16 post-FMT1 and 5 post-FMT2. Pro-inflammatory cytokines tumor necrosis factor-α (2.29 pg/mL→1.51 pg/mL), interferon (IFN)-γ (0.73 pg/mL→0.16 pg/mL) and interleukin (IL)-6 (9.40 pg/mL→3.60 pg/mL) decreased significantly, while anti-inflammatory IL-4 (0.97 pg/mL→1.16 pg/mL) and IL-10 (0.70 pg/mL→0.86 pg/mL) slightly increased. IL-2 and IL-1β rose mildly, and IL-8 elevated moderately. Sequential FMT restored gut Shannon diversity; principal coordinates analysis verified microbiota remodeling close to donor profiles, with reduced Escherichia-Shigella and enriched beneficial genera Faecalibacterium, Bacteroides and Ruminococcus.

CONCLUSION

In this patient, FMT combined with immunomodulatory nutrition was associated with restoration of gut microbiota, alleviation of symptoms, and improvement in nutritional and immune parameters in refractory radiation proctitis, suggesting a potential therapeutic strategy that warrants further validation.

Key Words: Radiation proctitis; Fecal microbiota transplantation; Gut microbiome; Immunomodulatory enteral nutrition; Gut barrier function; Case report

Core Tip: This case demonstrates that combining fecal microbiota transplantation (FMT) with immunomodulatory enteral nutrition can achieve sustained clinical remission in refractory radiation proctitis after only two FMT courses, outperforming previous FMT-alone reports that required 4-7 sessions. The concurrent restoration of gut microbiota diversity, enrichment of beneficial genera (Faecalibacterium, Ruminococcus, Bacteroides), and downregulation of pro-inflammatory cytokines suggest a synergistic effect of nutritional support and microbial reconstruction in radiation-induced intestinal injury. These preliminary observations, however, warrant confirmation in larger prospective studies.

INTRODUCTION

Radiation proctitis is a common intestinal complication associated with radiotherapy for the treatment of pelvic, abdominal, and retroperitoneal malignancies. The reported incidence varies widely across studies, with chronic radiation proctitis occurring in 5%-47% of patients with cervical cancer after radiotherapy[1]. Radiation proctitis is categorized into acute and chronic forms, based on the temporal pattern of symptom onset. Acute radiation proctitis typically occurs within 3 months of radiotherapy, predominantly affecting the superficial rectal mucosa, is generally self-limiting, and is associated with transient impairment of intestinal mucosal immunity that normalizes with the re-establishment of local immune homeostasis. Chronic radiation proctitis usually manifests 9-14 months after radiation exposure, with reported delays of up to 30 years. Pathologically, it is characterized by transmural involvement, fibrosis, and obliterative endarteritis driven largely by persistent immune dysregulation and chronic inflammation. Clinically, patients often experience severe abdominal pain, significant hematochezia, and potentially life-threatening complications, such as intestinal perforation, obstruction, or fistulae, all of which substantially diminish quality of life[2]. Current American Society of Colon and Rectal Surgeons list various treatments for chronic radiation proctitis, including topical formalin, sucralfate, and endoscopic argon plasma coagulations[3]. However, the efficacy of these conventional approaches is often unsatisfactory, highlighting the need for novel strategies directed toward the underlying immunopathological mechanisms. Radiotherapy significantly disrupts the gut microbiota, reducing Firmicutes and Bacteroidetes, increasing Proteobacteria, and depleting beneficial genera, such as Faecalibacterium and Lactobacillus[4]. This dysbiosis disrupts host-microbiota symbiosis and intestinal immune regulation, supporting microbiota-directed interventions as a rational therapeutic direction[5]. Probiotics have been shown to reduce the incidence of radiotherapy- and chemotherapy-related diarrhea[6]. However, probiotics typically introduce a limited number of exogenous strains and have a constrained capacity to fundamentally restructure a severely dysbiotic ecosystem. Fecal microbiota transplantation (FMT) offers a more comprehensive microbial reconstruction. Nevertheless, in case reports of FMT alone for radiation proctitis, required 4-7 sessions were required to achieve a clinical response, with residual symptoms in some patients[7,8], suggesting that FMT alone is not sufficient for sustained complete remission.

The efficacy of immunomodulatory enteral nutrition (IEN) in radiation enteritis remains controversial[9,10]. Although some studies have reported that formulations containing glutamine and omega-3 fatty acids may improve symptoms and immune parameters, others have failed to confirm clear benefits. These limitations suggest that IEN and FMT exert synergistic effects. Based on this rationale, we employed a sequential regimen of IEN followed by FMT in a patient with refractory radiation proctitis. This case provides initial evidence that addressing both immune dysregulation and microbiota disruption through combined nutritional and microbial intervention may be beneficial in refractory radiation proctitis. However, further studies are needed to validate these findings and to establish the generalizability of this approach.

CASE PRESENTATION

Chief complaints

A 49-year-old woman presented with a 3-month history of progressive abdominal pain, diarrhea, and hematochezia.

History of present illness

The patient reported progressive worsening of symptoms over 3 months, including severe lower abdominal cramping, frequent bloody mucoid stools, and persistent rectal tenesmus, which significantly impaired her function and quality of life. Her symptoms began shortly after completion of pelvic radiotherapy and gradually worsened over time. The timeline of fecal microbiota transplantation and efficacy is shown in Figure 1. Prior to referral, an external colonoscopy revealed signs of radiation-induced rectal injury, such as mucosal congestion, edema, hemorrhage, ulceration, and luminal stenosis, consistent with those described in evaluations of lower gastrointestinal bleeding. Histopathology of the rectal biopsies confirmed ischemic-type mucosal changes (Figure 2A, pre-FMT), supporting the diagnosis of radiation-induced vascular injury. Upon admission for refractory proctitis, comprehensive evaluation included intestinal microbiota analysis, which demonstrated profound dysbiosis with reduced alpha diversity and depletion of key commensals such as Faecalibacterium prausnitzii and Lactobacillus spp., which are patterns associated with impaired mucosal barrier function and immunity in radiation enteropathy.

Figure 1 Timeline of the fecal microbiota transplantation and efficacy. FMT: Fecal microbiota transplantation; EN: Enteral nutrition; WG: Weight gain; VRS: Vienna Rectoscopy Score; PG: Proctitis grading.

Figure 2 Representative colonoscopic and radiologic images of the patient before and after sequential fecal microbiota transplantation. A: Colonoscopic view before fecal microbiota transplantation (FMT), showing mucosal congestion, edema, hemorrhage, ulceration, and luminal stenosis; B: Colonoscopic view at 1 month after the first FMT, showing notable improvement in mucosal inflammation compared with baseline; C: Colonoscopic view at 2 months after the second FMT, showing nearly normal mucosa with only mild residual changes; D: Abdominal Xray confirming the placement of the nasojejunal tube for FMT administration; E: Intraoperative endoscopic view confirming tube patency after flushing with normal saline before scope withdrawal; F: Abdominal Xray verifying the stable position of the nasojejunal tube after FMT. pre-FMT: Baseline before fecal microbiota transplantation; FMT-1: 1 month after the first fecal microbiota transplantation; FMT-2: 2 months after the second fecal microbiota transplantation.

History of past illness

The patient had a history of cervical cancer treated with radical hysterectomy 4 years prior. One year before the current presentation, she developed left inguinal lymph node metastasis and subsequently received pelvic radiotherapy (50 Gy in 25 fractions).

Personal and family history

No significant family history of gastrointestinal disease or malignancy was reported.

Physical examination

Physical examination revealed mild to moderate lower abdominal tenderness without peritoneal signs.

Laboratory examinations

Laboratory testing revealed chronic inflammation and malnutrition: Hemoglobin 112 g/L, lymphopenia (0.94 × 10⁹/L), and hypoalbuminemia (35.8 g/L).

Imaging examinations

Colonoscopy confirmed active proctitis with erythema, edema, hemorrhage, ulcerations, and luminal narrowing, and computed tomography revealed rectal wall thickening without fistulas. Endoscopic lesions were graded by the Vienna Rectoscopy Score (VRS, Table 1). Definitions of endoscopic findings are as follows. Congested mucosa: Grade 0 (no congestion); Grade 1 (localized mucosal redness and edema); Grade 2 (diffuse, non-confluent mucosal redness and edema); Grade 3 (diffuse, confluent mucosal redness and edema). Telangiectasia: Grade 0 (none); Grade 1 (single telangiectasia); Grade 2 (multiple non-confluent telangiectasias); Grade 3 (multiple confluent telangiectasias). Ulceration: Grade 0 (none); Grade 1 (minute ulcers with an area < 1 cm²); Grade 2 (ulcers with an area > 1 cm²); Grade 3 (deep ulcers); Grade 4 (deep ulcers complicated by fistula or perforation). Stricture: Grade 0 (none); Grade 1 (luminal diameter > 2/3 of original); Grade 2 (luminal diameter 1/3-2/3 of original); Grade 3 (luminal diameter < 1/3 of original); Grade 4 (complete obstruction). Necrosis: Grade 0 (none); Grade 1 (present). The total VRS ranges from 0 to 5 according to the overall severity of rectal mucosal injury. In addition, clinical severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE, Table 2), and the patient was classified as CTCAE grade 3 proctitis at baseline.

Table 1 Vienna Rectoscopy Score.

Score	Congested mucosa	Telangiectasia	Ulceration	Stricture	Necrosis
0	Grade 1	None	None	None	None
1	Grade 2	Grade 1	None	None	None
2	Grade 3	Grade 2	None	None	None
3	Any grade	Grade 3	Grade 1	None	None
4	Any grade	Any grade	Grade 2	Grade 1	None
5	Any grade	Any grade	≥ Grade 3	≥ Grade 2	Present

Full grading definitions of the Vienna Rectoscopy Score are detailed in the main text.

Table 2 Common terminology criteria for adverse events of radiation proctitis.

Grade	Clinical standards and intervention measures
Grade 1	Rectal discomfort; intervention not indicated
Grade 2	Symptoms (e.g., rectal discomfort, passing blood or mucus); medical intervention indicated; limiting instrumental activities of daily living
Grade 3	Severe symptoms; fecal urgency or stool incontinence; limiting self-care activities of daily living
Grade 4	Life-threatening consequences; urgent intervention indicated
Grade 5	Death

MULTIDISCIPLINARY EXPERT CONSULTATION

Multidisciplinary expert consultation was carried out for this patient. Gastroenterology, nutrition and critical care specialists jointly formulated sequential microbiota-nutrition therapy, guiding the whole treatment and follow-up management.

FINAL DIAGNOSIS

A diagnosis of refractory radiation proctitis with severe gut dysbiosis was made.

TREATMENT

FMT donor screening and bacterial suspension preparation were performed according to strict standard protocols[11]. Two healthy juvenile donors, aged 8 years and 11 years, without any gastrointestinal discomfort, infectious diseases, or relevant family history were enrolled. All serological and stool pathogen screenings tests yielded negative results in these donors, and neither took antibiotics, probiotics or flora-interfering drugs for 4 weeks prior to stool donation. Both maintained balanced daily diets. After admission and baseline assessment, the patient underwent intestinal preconditioning with oral vancomycin and rifaximin followed by polyethylene glycol bowel cleansing. A nasojejunal tube was placed for enteral nutrition support prior to the first FMT; enteral nutrition was initiated on April 23 at 30 mL/hour and titrated to 1000 mL daily. FMT was administered on April 25 with concurrent probiotics, prebiotics, and continuous enteral nutrition. One month after the first FMT, follow-up colonoscopy showed notable improvement in mucosal inflammation compared with baseline (Figure 2B). Given the persistent but milder residual symptoms, a second FMT was performed. Two months after the second FMT, colonoscopy revealed nearly normal mucosa with only mild residual changes (Figure 2C). The nasojejunal tube position was confirmed by abdominal radiography (Figure 2D). During FMT administration, tube patency was confirmed by intraoperative endoscopy after flushing with normal saline before scope withdrawal (Figure 2E), and abdominal radiography verified the stable position of the transendoscopic enteral tubing) after FMT (Figure 2F).

Statistical analyses

16S rRNA V3-V4 sequencing was conducted using an Illumina NovaSeq 6000, generating approximately 20000 valid reads per sample with saturated rarefaction curves. Raw data were processed in QIIME2-DADA2 to generate amplicon sequence variants, with taxonomy assigned against SILVA v138.1 (99% identity). The Shannon index reflected longitudinal α-diversity, while the Bray-Curtis PCoA was used to visualize β-diversity, shown in Figure 3A and B. As only one sample was collected per time-point in this single-case study, intergroup statistical comparisons were unavailable; instead, genus-level microbial shifts were interpreted descriptively. The taxonomic profiles of the patient and two donors are shown in Figure 3C and D.

Figure 3 Microbiome analysis of the patient before and after sequential fecal microbiota transplantation. A: α-diversity represented by the Shannon diversity index, showing changes in gut microbial richness across pre-fecal microbiota transplantation (FMT), FMT-1, FMT-2, and donor samples; B: β-diversity analyzed via principal coordinates analysis, illustrating dissimilarities in microbial community structure; C: Taxonomic classification of gut microbiota at the phylum level; D: Taxonomic classification of gut microbiota at the genus level. pre-FMT: Baseline before FMT; FMT-1: 1 month after the first FMT; FMT-2: 2 months after the second FMT; PCoA: Principal coordinates analysis; Donor1/Donor2: Fecal microbiota donors.

OUTCOME AND FOLLOW-UP

Three days after the first FMT, the patient exhibited improvements in sleep quality, mental status, abdominal pain and diarrhea. By day 7, abdominal pain had fully resolved, permitting morphine withdrawal, accompanied by a 2 kg increase in body weight. At hospital discharge, the patient reported mild residual abdominal pain, with 2-3 daily mucoid, non-hemorrhagic stools, and persistent improvements in sleep and mental function. Oral enteral nutrition plus synbiotic supplementation was initiated post-discharge.

Oral enteral nutrition was maintained between the two FMT sessions to facilitate weight restoration and mucosal repair. At 1 month following the initial FMT, abdominal pain was substantially relieved, and bowel habits stabilized to 2-3 daily mucoid stools, corresponding to a 5 kg weight gain relative to baseline (Figure 1). Repeat colonoscopy demonstrated substantial amelioration of mucosal inflammation (Figure 2B); the VRS declined from 25 to 16, and radiation proctitis regressed from CTCAE grade 3 to grade 2 (Table 3). The patient received the second FMT on June 7, 2024 (Figure 2E).

Table 3 Baseline characteristics.

	Pre-FMT	FMT1	FMT2
BMI (kg/m2)	20.28	22.31	24.34
Total protein (g/L)	63.7	68.3	73.7
Albumin (g/L)	35.8	36.7	40.0
Hemoglobin (g/L)	112	120	122
Lymphocyte count (109/L)	0.94	1.14	1.37
White blood cell count (109/L)	5.17	3.54	3.94
Lymphocyte percentage (%)	18.2	32.1	34.8
Vienna Rectoscopy Score	25	16	5
Proctitis grading (CTCAE grade)	Grade 3	Grade 2	Grade 1
PCT (ng/mL)	0.07	0.06	0.03

Pre-FMT: Before fecal microbiota transplantation; FMT1: Colonoscopy reexamined 1 month after the first fecal microbiota transplantation course; FMT2: Colonoscopy reexamined 2 months after the second fecal microbiota transplantation course; BMI: Body mass index; VRS: Vienna Rectoscopy Score; PCT: Procalcitonin; CTCAE: Common Terminology Criteria for Adverse Events.

Two months after the second FMT, the patient achieved complete symptomatic remission, with a total body weight gain of 10 kg (Body mass index, 24.34 kg/m²). Serum laboratory markers (hemoglobin and albumin) returned to normal ranges (Table 3), and colonoscopy revealed nearly restored mucosal architecture (Figure 2C); the VRS decreased to 5, and radiation proctitis improved to CTCAE grade 1 (Figure 1 and Table 3). Sustained clinical remission was maintained across the entire 12-month follow-up period, with no FMT-related adverse events documented.

Sequencing of the 16S rRNA gene (V3-V4) from serial fecal samples revealed a substantial restructuring of the microbiota. Alpha diversity (Shannon index) increased significantly post-FMT and peaked after the first transplantation (Figure 3A). PCoA showed a clear separation between the patient’s pre treatment microbiota and those of the donors, with rapid convergence toward the profile of Donor 1’s profile after the first FMT, indicating successful engraftment (Figure 3B).

At the phylum level, the pretreatment microbiota was characterized by a high abundance of Proteobacteria. After the first FMT, the abundance of Proteobacteria decreased markedly, Firmicutes increased substantially, and Actinobacteria and Bacteroidetes increased. Following the second FMT, Firmicutes and Bacteroidetes increased further, with Firmicutes approaching the levels observed in Donor 2 (Figure 3C).

Genus-level analyses confirmed the profound ecological shifts. Opportunistic pathogens (e.g., Escherichia-Shigella, and Enterobacter) were dominant before treatment and declined markedly post-FMT. Beneficial genera, including Ruminococcus, Bacteroides, Faecalibacterium, Collinsella, Megamonas, and Bifidobacterium, increased substantially after the first procedure. After the second FMT, Ruminococcus, Bacteroides, and Faecalibacterium remained enriched, whereas Bifidobacterium, Megamonas, and Collinsella decreased slightly, reflecting ongoing ecological dynamics after the introduction of the microbiota from a different donor (Figure 3D).

After FMT intervention, the overall Kyoto Encyclopedia of Genes and Genomes (KEGG) functional profiles of the gut microbiota exhibited substantial remodeling. Pathways related to amino acid (AA) metabolism, metabolism of cofactors and vitamins, translation, and protein families for genetic information processing gradually increased, with their relative abundances rising from 5.72%, 3.43%, 2.00%, and 14.26% at baseline (pre-FMT) to 6.01%, 3.90%, 2.82%, and 16.87% at the second FMT time- point (FMT-2), respectively. In contrast, membrane transport and protein families participating in signaling and cellular processes declined progressively, with relative abundances dropping from 5.10% and 17.19% at pre-FMT to 3.69% and 14.41% at FMT-2 (Figure 4). Taken together, these functional alterations indicated that the microbial functional landscape shifted from a signaling- and stress-response-dominant phenotype toward a profile enriched in biosynthetic and mucosal reparative pathways, consistent with the alleviated intestinal inflammatory injury observed clinically.

Figure 4 Predicted Kyoto Encyclopedia of Genes and Genomes level 2 functional profiles of the patient before and after fecal microbiota transplantation. A: Relative abundances of Kyoto Encyclopedia of Genes and Genomes level 2 pathways across pre-fecal microbiota transplantation (FMT), FMT-1, FMT-2, and two donor samples (Donor1, Donor2), grouped by level 1 categories (Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, Human Diseases, Brite Hierarchies, and Unclassified); B: Detailed abundance patterns of individual level 2 pathways, highlighting functional modules with notable shifts after FMT. Predictions were generated using PICRUSt2 from 16S rRNA sequencing data. pre-FMT: Baseline before fecal microbiota transplantation; FMT-1: 1 month after the first fecal microbiota transplantation; FMT-2: 2 months after the second fecal microbiota transplantation; Donor1/Donor2: Fecal microbiota donors.

MetaCyc pathway functional prediction was performed using PICRUSt2 based on serial fecal 16S rRNA sequencing data. As shown in Figure 5A, FMT induced marked shifts in the abundance of multiple MetaCyc pathways, reflecting broad gut microbiome functional remodeling. Annotated pathways were grouped into five core functional classes (Figure 5B): AA synthesis, short-chain fatty acid (SCFA) synthesis, carbohydrate metabolism, lipid metabolism, and toxic degradation. AA synthesis and carbohydrate metabolism exhibited sustained enrichment (AA: 3.80%→4.38%→4.88%; carbohydrate: 3.80%→3.97%→4.49%). SCFA synthesis peaked at FMT-1 and then decreased slightly dropped at FMT-2 (1.10%→1.42%→1.26%). Lipid metabolism remained low after FMT (2.93%→ 2.78%→3.21%), while toxic degradation pathways decreased drastically and remained low throughout follow-up (0.78%→0.19%→0.22%) (Figure 5). Together with the recovered gut microbial composition described above, these functional changes indicate the reconstruction of a metabolically balanced gut microecosystem post-FMT.

Figure 5 Temporal shifts in MetaCyc pathway abundances of the patient’s gut microbiome pre- and post-faecal microbiota transplantation. A: Z-score normalized heatmap showing MetaCyc pathway abundance dynamics at pre-fecal microbiota transplantation (FMT), FMT-1 and FMT-2 (orange = upregulation, blue = downregulation); B: Aggregated relative abundances of five core functional categories: Branched-chain amino acid synthesis, short-chain fatty acid synthesis, carbohydrate metabolism, lipid metabolism, and toxic degradation. Functional profiles were predicted via PICRUSt2 from serial 16S rRNA sequencing data; all analyses are descriptive owing to the single-case design. AA: Amino acid; SCFA: Short-chain fatty acid; pre-FMT: Baseline before fecal microbiota transplantation; FMT-1: 1 month after the first fecal microbiota transplantation; FMT-2: 2 months after the second fecal microbiota transplantation.

As shown in Figure 6, the levels of pro-inflammatory cytokines decreased substantially after treatment: Tumor necrosis factor-α (TNF-α) declined from 2.29 pg/mL to 1.51 pg/mL, interferon (IFN)-γ from 0.73 pg/mL to 0.16 pg/mL, and interleukin (IL)-6 from 9.40 pg/mL to 3.60 pg/mL. Concurrently, anti-inflammatory cytokines showed slight elevations: IL-4 increased from 0.97 pg/mL to 1.16 pg/mL, and IL-10 from 0.70 pg/mL to 0.86 pg/mL. Further, IL-2 and IL-1β levels rose slightly, while IL-8 showed a moderate elevation within the physiological range.

Figure 6 Dynamic changes of serum cytokines at baseline and post microbiota-nutrition sequential therapy. A: Profiles of six low-abundance cytokines. Pro-inflammatory interferon-γ and tumor necrosis factor-α markedly declined after treatment, whereas anti-inflammatory interleukin (IL)-4 and IL-10 slightly increased, with mild elevation of IL-2 and IL-1β; B: Variation of high-level pro-inflammatory cytokines IL-6 and IL-8: IL-6 decreased obviously, while IL-8 slightly rose within physiological range. X-axis: Baseline, post two cycles of combined therapy; Y-axis: Cytokine concentration (pg/mL). TNF-α: Tumor necrosis factor-α; IL: Interleukin; IFN-γ: Interferon-γ.

DISCUSSION

This case demonstrates that sequential IEN combined with FMT induces sustained remission in chronic radiation proctitis. The daily stool frequency decreased from 7-8 to 2 after the first FMT, diarrhea resolved completely post-second FMT, and all clinical benefits persisted over 1year followup.

IEN preserves intestinal barrier integrity by maintaining tightjunction structure, reducing permeability, and limiting bacterial/endotoxin translocation, thereby mitigating systemic inflammation[12]. Its n3 PUFAs (EPA/DHA) suppress proinflammatory cytokines (IL-6, and TNF-α) via competitive inhibition of arachidonic acid metabolism and PPARγ/NF-κB pathway activation[13,14], while glutamine, arginine, and nucleotides synergistically promote epithelial repair and mucosal regeneration[12]. Additionally, IEN enhances gut-associated lymphoid tissue (GALT) function and secretory IgA (sIgA) synthesis, reinforcing mucosal immune defenses-critical for radiationdamaged mucosa with impaired integrity and immunity. Consistent with these mechanisms, postFMT immunological shifts in this patient (reduced TNF-α, IFN-γ, IL-6, and procalcitonin and elevated IL-4, and IL-10) indicated alleviated systemic inflammation and enhanced mucosal immunity.

Cumulative evidence confirms that radiotherapy disrupts intestinal function and gut microbial composition, resulting in a marked reduction in microbial richness[15]. These alterations lead to the depletion of beneficial commensals and overgrowth of opportunistic pathogens, which occupy intestinal ecological niches and inhibit colonization of normal flora. This dysbiotic microenvironment triggers endotoxin leakage and exacerbates intestinal inflammation and mucosal lesions[16]. A systematic review further indicated that radiation-driven dysbiosis elevates pro-inflammatory cytokines (e.g., IL-1β) and impairs epithelial barrier integrity, amplifying intestinal tissue injury[17]. As shown in Figure 3, the patient’s pre-treatment microbiota exhibited lower alpha diversity than those of two healthy donors, characterized by dominant Proteobacteria and depleted Firmicutes and Bacteroidetes. Our findings are consistent with those of Wang et al[4], who reported identical microbial shifts in patients after pelvic radiotherapy, including elevated Proteobacteria and Fusobacteria and reduced Firmicutes and Bacteroidetes. Notably, Proteobacteria harbors multiple pathogenic genera, such as Escherichia-Shigella and Enterobacter, and these become dominant in the gut after radiation exposure[18,19].

Combined FMT and enteral nutrition persistently suppressed pathogenic Enterobacteriaceae while enriching protective genera, including Ruminococcus, Bacteroides, and Faecalibacterium. This phenotype aligns with preclinical animal data demonstrating that FMT alleviates radiation enteritis by reshaping the microbiota and metabolic profiles, including the expansion of beneficial taxa (Blautia wexlerae and Romboutsia timonensis) and reprogramming of nicotinate and fatty acid metabolic pathways[20].

A MetaCyc pathway analysis uncovered the metabolic basis of this compositional remodeling. AA synthesis pathways rose steadily after FMT, whereas SCFA synthesis peaked transiently at FMT-1 before a slight decline at FMT-2. KEGG functional profiling further revealed a functional transition from stress/signaling dominance toward biosynthetic and mucosal reparative pathways, consistent with the clinical attenuation of intestinal inflammatory damage.

Regenerated core commensals exert distinct protective effects. Ruminococcus degrades resistant starch to produce SCFAs, facilitating mucosal repair and counteracting radiation injury via NF-κB inhibition and reductions in pro-inflammatory mediators[20]. As a key anti-inflammatory commensal, Faecalibacterium prausnitzii produces SCFAs to sustain colonocyte survival, dampen inflammation and reinforce gut barrier function; its abundance is inversely correlated with intestinal inflammation, making it a therapeutic target for nutritional and probiotic interventions[17]. Bile salt hydrolase from Ruminococcus and Lactobacillus maintains bile acid homeostasis, while radiation-related depletion of Bacteroides disrupts this balance and contributes to severe diarrhea. Restoration of these key commensal populations explains the sustained clinical remission observed post-FMT[21].

SCFAs are pivotal immunoregulatory microbial metabolites. Butyrate, a representative SCFA, activates G protein-coupled receptors to stabilize the gut microbiota and alleviate radiation-induced intestinal damage, with its anti-inflammatory effects linked to preserved small intestinal villi and goblet cells[22]. Consistent with this, exogenous supplementation of microbiota-derived butyrate effectively mitigated abdominal irradiation-induced intestinal injury in preclinical models, validating the therapeutic value of butyrate for radiation enteritis[23]. There is substantial evidence for the protective roles of the gut microbiota and SCFA metabolites against radiation intestinal injury[24].

Compared with previous FMT-alone case reports for radiation proctitis[7,8,18], our sequential strategy offers several distinct advantages. The use of repeated FMT alone to modify the gut microbiota does not fully address mucosal barrier injury or immune dysregulation. Our regimen employed IEN (glutamine and n-3 PUFAs) as a preconditioning strategy to repair the mucosal barrier and suppress local inflammation, optimizing the microenvironment for FMT engraftment and achieving synergistic nutritional-microbiota intervention. Regarding the efficacy assessment, prior reports have predominantly used subjective symptoms or colonoscopic descriptions, while our study quantified mucosal healing via the VRS and systematically tracked nutritional, immune, and inflammatory cytokine parameters, all of which showed significant improvements, supported by 16S rRNA sequencing, which demonstrated reduced pathogenic Escherichia-Shigella and enriched beneficial Faecalibacterium, Bacteroides, and Ruminococcus. Regarding efficiency, Zheng et al[7] required four courses, while Liu et al[8] required seven sessions; conversely, our regimen achieved CTCAE grade 3→1 after only two courses. Additionally, Wang et al[18] reported residual hematochezia post-FMT, while our patient achieved a nearly normal mucosa with complete remission, indicating that nutritional preconditioning enhances engraftment and durability. Collectively, these findings support the emerging paradigm that combining nutritional support with microbiota-targeted interventions may offer synergistic benefits for radiation enteritis. Our sequential therapy simultaneously targets “mucosal repair-, immune modulation-, and microbiota reconstruction”, demonstrating superiority in therapeutic concept, evaluation depth, and clinical efficacy over FMT alone.

The proposed synergistic mechanisms are summarized in Figure 7. Overall, IEN provides multi-target protection-EPA/DHA exerts anti-inflammatory effects via PPAR-γ/NF-κB inhibition, glutamine repairs the intestinal barrier, arginine improves microcirculation, and nucleotides promote epithelial regeneration. FMT enriches SCFA-producing genera (Faecalibacterium, Ruminococcus, and Bacteroides) and reduces opportunistic pathogens. SCFAs, together with nutritional substrates, reinforce tight junctions, suppress inflammation, activate GPCR signaling to mitigate fibrosis, and enhance mucosal immunity through GALT and sIgA. This integrated framework illustrates how nutritional and microbial interventions converge to restore intestinal homeostasis.

Figure 7 Schematic illustrating synergistic mechanisms of faecal microbiota transplantation plus immunomodulatory enteral nutrition against radiation enteritis. Faecal microbiota transplantation remodels gut microbiota to enrich beneficial Ruminococcus, Bacteroides, Faecalibacterium, reduce pathogenic Escherichia-Shigella and Enterobacter, and boost intestinal short-chain fatty acid (SCFA) levels. EPA, DHA, glutamine, arginine and nucleotides exert multi-target protection. SCFAs combined with these nutrients strengthen tight junctions, suppress NF-κB-driven inflammation, activate GPCR signaling to mitigate intestinal fibrosis, and enhance mucosal immunity via elevated gut-associated lymphoid tissue activity and secretory IgA secretion. Combined therapy relieves abdominal pain, diarrhea and hematochezia, and restores intact intestinal mucosa. GALT: Gut-associated lymphoid tissue; sIgA: Secretory IgA.

Limitations

Several limitations should be acknowledged. This is a single-case report without a control group, precluding causal inference and generalizability. Multiple concurrent interventions (antibiotics, probiotics, prebiotics, bowel preparation, and enteral nutrition alongside FMT) make it difficult to isolate the independent contribution of each component. Functional microbiome analyses (e.g., metabolomics for SCFAs, bile acids, and tryptophan metabolites) were not performed, leaving metabolic mechanisms speculative. We also did not evaluate intestinal permeability markers, post-treatment histopathology, and immune cell subsets. Owing to the single-case design with one sample per time- point, inferential statistics for microbiome changes were not applicable. Longitudinal microbiome data beyond 2 months were unavailable. Our findings should therefore be interpreted as hypothesis-generating; larger prospective studies are warranted to confirm efficacy, safety, and mechanisms.

CONCLUSION

Overall, this case report outlines a sequential strategy of EN followed by FMT for the management of refractory radiation proctitis. EN provides targeted nutritional support to promote mucosal repair and improve the local microenvironment; subsequently, FMT delivers a functional microbial consortium that helps restore gut ecology and suppress opportunistic pathogens. The two interventions appear to act synergistically-nutrition facilitates mucosal healing and microbial engraftment, while the reconstituted microbiota further enhances barrier integrity and absorption. This combined nutritional-ecological approach may represent a promising strategy for refractory radiation-induced intestinal injury; however, these findings remain preliminary, and the broader applicability of our strategy requires further validation in large-scale prospective randomized controlled trials.

ACKNOWLEDGEMENTS

We sincerely thank the patient for participating in this study and providing serial fecal samples for microbiota analysis.