The Relationship Between Microbiota, Nutrition, and Gastrointestinal Tract Symptoms in Patients with Systemic Sclerosis: A Systematic Review of the Literature
Abstract
1. Introduction
2. Materials and Methods
2.1. Information Sources and Search Strategy
2.2. Eligibility Criteria
2.3. Selection Process
2.4. Data Extraction, Date Items, and Result Synthesis
2.5. Quality Assessment
3. Results
3.1. Study Selection
3.2. Study Characteristics
3.3. Relationship Between Gut Microbiota and Gastrointestinal Involvement
Ref | Sample Size | Age (yrs) | Comparison Group | GM Composition | GM and GI Symptoms’ Relation |
---|---|---|---|---|---|
[11] | 17 SSc | 52.1 [46.6–63.0] | SSc vs. HCs | ↑ Fusobacterium, γ-Proteobacteria (potential pathobiont) ↑ Bifidobacterium, Lactobacillus ↓ Faecalibacterium, Clostridium (commensal bacteria) | N/A |
17 HCs | 55.0 [51.0–62.0] | SSc/GI+ vs. SSc/GI− | N/A | ↑Fusobacterium ↓Bacteroides fragilis | |
[12] | 9 SSc/GI+ | 55.3 [36–79] | SSc/GI− vs. HCs | ↑ Streptococcus salivarius | N/A |
9 SSc/GI− | 57.4 [34–78] | SSc/GI+ vs. HCs | N/A | ↑ Lactobacillus, Eubacterium, Acinetobacter ↓ Roseburia, Clostridium, Ruminococcus | |
9 HCs | 54.8 [26–78] | SSc/GI− vs. SSc/GI+ | N/A | ↑ Streptococcus salivarius | |
[13] | 59 SSc | 56.5 ± 12.7 | SSc vs. HCs | ↓ protective butyrate-production bacteria ↑ proinflammatory noxius genera (Desulfovibrio) | N/A |
29 HCs | 49.3 ± 12.9 | SSc/GI+ vs. HCs | N7A | 10 different genera between HCs, SSc/GI+, and SSc/GI | |
[14] | 63 SSc | 52.5 ± 14.2 | SSc vs. HCs | ↑Firmicutes philum, Streptococcus, Lactobacillus, Blautia, Ruminococcus, Phascolarctobacterium genera ↓Sutterella, Bacteroides, Odoribacter, Roseburia genera | N/A |
17 HCs | 50.8 ± 14.3 | ||||
[15] | 19 SSc | 51.3 [48.7–59.4] | ↑ Bacteroides, Prevotella, genera from the Clostridiales order | Bacteroides → Total GI symptoms Prevotella → Diarrhea Genera from Clostridiales order →Distension/ bloating | |
[16] | 106 SSc 85 HCs | 55.3 ± 15.9 | SSc vs. HCs | ↓ Commensal genera (e.g., Faecalibacterium) ↑ Pathobiont genera (e.g., Desulfovibrio) | SIBO as indicator of dysbiosis in several sites of GI tract |
[17] | 66 SSc | 55.4 ± 11.8 | SSc/GI+ vs. SSc/GI− | N/A | ↑ Klebsiella, Enterococcus |
Non-low FODMAP vs. low FODMAP | ↑ Enterococcus | Similar microbial composition and GI symptoms | |||
[18] | 26 SSc | 64.8 ± 11.9 | SSc vs. HCs | ↑ Acidaminococcaceae and Sutterellaceae families ↓Peptostreptococcaceae family, Anaerostipes, Blautia, Romboutsia, and Turicibacter genera | N/A |
18 VEDOSS | 51.7 ± 16.1 | VEDOSS vs. HCs | ↓ Bacilli class, Blautia, Romboutsia, Streptococcus, Turicibacter | N/A | |
20 HCs | 50.8 ± 14.3 | VEDOSS vs. SSc | N/A | N/A |
Ref | Study Design | Sample Size | Age (yrs) | SSc Severity | Intervention Group n (Females) | Comparison Group n (Females) | Treatment Duration | Effects on GI Symptoms |
---|---|---|---|---|---|---|---|---|
[19] | Perspective study. Participants were supplemented with either Align (Bifidobacterium infantis; 10^9 CFU per capsule) or Culturelle (Lactobacillus GG; 10^9 CFU per capsule) once a day | 10 SSc | 51.7 | UCLA STCT GIT 2.0 total score 1.25–3.00 | 10 (9) | - | 2 months supplementation | Improvement in total GIT 2.0 score, reflux, bloating/distention, and emotional scales |
[20] | RCT placebo controlled. Participants were randomized (1:1) to receive 60 days of high dose multi-strain probiotics (Vivomixx 1800 billion units/day) or identical placebo, followed by an additional 60 days of probiotics in both groups | 40 SSc | UCLA STCT GIT 2.0 total score > 0.10 | 19 (19) | 21 (16) | 60 + 60 days | No change in UCLA STCT GIT 2.0 after 60 or 120 days of treatment Significant improvement in GI-reflux after 120 days | |
21 Placebo-Probiotics | 50.7 ± 8.0 | |||||||
19 Probiotics-Probiotics | 51.4 ± 13.7 | |||||||
[21] | RCT placebo controlled. Participants were randomly assigned to receive a daily dose of probiotics (Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophillus, and Bifidobacterium lactis, 10^9 CFU per capsule) or placebo for 8 weeks | 73 SSc | UCLA STCT GIT 2.0 total score > 0.50 | 37 (34) | 36 (34) | 8 weeks | No difference in the UCLA STCT GIT 2.0 score after 8 weeks Probiotic group: ↓ Th17 No difference in the Th1, Th2 and regulatory T cells No difference in HAQ-DI score | |
37 Probiotic group | 46.7 ± 13.1 | |||||||
36 Placebo | 47.1 ± 11.9 | |||||||
[22] | A double-blind, placebo-controlled pilot study | 9 SSc | 62.0 ± 5.7 | UCLA STCT GIT 2.0 total score 0.72 ± 0.5 | 5 FMT | 4 Placebo | 16 week after FMT | FMT with ACHIM reduces lower GI symptoms, altering the GM |
[23] | A phase 2 randomised, double-blind, placebo-controlled study | 67 SSc | 58.9 ± 11.5 | UCLA STCT GIT 2.0 total score 0.9 ± 0.5 | 33 (33) ACHIM | 34 (29) Placebo | 12 week after FMT | No change in lower GI symptoms after FMT |
3.4. Relationship Between Malnutrition and Gastrointestinal Involvement
Ref | Total Sample and Subgroups | Age (yrs) | Criteria, and Total Score of GI Involvement | n (%) of GI Involvement | Malnutrition Criteria | Malnutrition Associations |
---|---|---|---|---|---|---|
[8] | 24 SSc | 54 ± 13 | UCLA SCTC GIT 2.0 | 17 (71) | MUST SGA | Malnutrition risk prevalence: 37.5% (MUST) Malnutrition prevalence: 50% (SGA) Malnutrition status was associated with total UCLA SCTC GIT 2.0 score, reflux, distention/bloating, soilage, diarrhea, social function, and emotional well-being |
[24] | 160 SSc | 61.7 [53.9–68.0] | Medsger's severity scale | 82 (51.2) | BMI | Malnutrition prevalence: 15% Malnutrition was associated with disease activity, low serum prealbumin, but not with GI involvement |
24 Malnourished patients | 61.7 [54.0–67.9] | 16 (66.7) | ||||
136 No- malnourished patients | 61.1 [47.2–68.5] | 66 (48.5) | ||||
[25] | 52 SSc 51 HCs | N/A | N/A | N/A | BMI | SSc patients have a lower BMI BMI was associated to quality of life, but not to GI symptoms. GI symptoms was associated with life quality No associations between low BMI and upper GI symptoms (heartburn, nausea, vomiting, dysphagia, and epigastric pain) |
[26] | 129 SSc | 59.1 ± 13.8 | N/A | N/A | MUST | Malnutrition risk prevalence: 10.9%. Malnutrition was associated with the quality of life |
[27] | 141 SSc | 63 ± 13 | UCLA SCTC GIT 2.0 | 16 (11.3) | ESPEN | Malnutrition prevalence: 9.2% Sarcopenia prevalence: 20.7% Malnutrition is associated with GI symptoms, low muscularity, reduced FVC, and DLCO Malnutrition and sarcopenia affect disease severity, especially for the lung |
[28] | 120 SSc | 64 ± 15 | N/A | 111 (93) | MUST PNDS | Malnutrition prevalence: 59.2% Malnutrition risk: 58% Malnutrition was associated with cardiac involvement, number of GI organs involved, gastroesophageal reflux disease, chronic intestinal pseudo obstruction |
[29] | 62 SSc | 62 [32–78] | N/A | 26 (42) esophageal involvement | ESPEN | Malnutrition prevalence: 19% Sarcopenia prevalence: 42% (RSMI) and 55% (HGS) Sarcopenia was associated with esophageal involvement |
[30] | 176 Established SSc | 58 [49–67] | UCLA SCTC GIT 2.0 | 231 (92.4) | EUSTAR | Malnutrition prevalence: 48.3% Micronutrients deficiences were very common, especially in folic acid, selenium, prealbumin, and zinc Micronutrient deficiencies was associated with low BMI, but not with GI involvement, except for prealbumin |
74 early SSc | 52 [38–61] | |||||
[31] | 36 postmenopausal female patients with SSc | N/A | N/A | 12 (33) | ESPEN | Malnutrition prevalence: 36.1% ↓weight, BMI, hemoglobin, albumin, parathyroid hormone, 25-hydroxyvitamin D, lumbar spine T-score, bone mineral density values, and trabecular bone score values Bone status correlated with serum biomarkers of malnutrition, and GI symptoms |
13 Malnourished patients | 54 [43–75] | |||||
23 Non-malnourished patients | 66 [43–85] | |||||
[32] | 134 SSc | 50.2 ± 12.3 | UCLA SCTC GIT 2.0 (0.24 ± 0.27) | 20 (15) | MUST | Malnutrition risk prevalence: 15% Malnutrition was associated with limited pulmonary function, lung involvement, pulmonary hypertension, capillary rarefaction Capillary rarefaction was independently associated with medium to high malnutrition risk Capillary rarefaction and severe skin involvement were determining factors for malnutrition and GI symptoms |
[33] | 56 SSc | 54.1 ± 11.9 | N/A | 43 (76.8) | ESPEN 7-SGA SNAQ GLIM | Malnutrition prevalence: 17.9% (ESPEN 2015), 23.2% (7-SGA), 16.1% (SNAQ), and 62.5% (GLIM) Malnutrition was associated with GI symptoms |
[34] | 98 SSc | 52.7 ± 11.3 | N/A | 14 (14.6) | MUST | Malnutrition prevalence: 100% (including both in- and outpatients) Malnourished patients had high mRSS Malnutrition risk was associated with interstitial lung disease and bowel involvement, and depressive symptoms, but not with GI symptoms |
[35] | 168 SSc | 61 [25–81] | UCLA SCTC GIT 2.0 (0.9 ± 0.9) | N/A | MUST | Malnutrition prevalence: 16% BMI was associated with small intestinal involvement and disease severity |
[36] | 102 SSc | 55 ± 14 | N/A | N/A | GLIM ESPEN | Malnutrition prevalence: 8.8% (ESPEN), 16.6% (GLIM) According to GLIM, disease activity index and disease severity scale were associated with malnutrition, but not for ESPEN Malnutrition was not associated with GI symptoms |
[37] | 60 SSc | 53 [43–63] | UCLA SCTC GIT 2.0 (0.53 [0.19–0.89]) | 9 (13) | ESPEN GLIM | Malnutrition prevalence: 11.6% (ESPEN), 23.2% (GLIM) FFMI, but not malnutrition, was associated with GI symptoms (distension/bloating) |
[38] | 101 SSc | 55 [47–66] | N/A | 10 (9.9) | GLIM | Malnutrition prevalence: 21.8% Malnutrition according GLIM criteria was associated with GI symptoms, hospitalization, and survival |
[39] | 100 SSc | 62 [53–70] | UCLA SCTC GIT 2.0 (0.18 [0.04–0.41]) | 20 (20) | GLIM | Malnutrition prevalence: 29% Malnourished patients had increased GI symptoms. GI symptoms was associated with depression score (cognitive impairment prevalence: 50% according Montreal Cognitive Assessment). Malnutrition was associated with age, dysphagia, and mRSS |
[40] | 75 SSc | 59.6 ± 10.6 | UCLA SCTC GIT 2.0 (0.5 [0.2–1.1]) | 44 (58) | MNA- SF | Malnutrition prevalence: 30.7% Malnutrition was associated with severe GI symptoms, poor quality of life, and skin involvement |
[41] | 1903 SSc | 47.3 [36.4–57.0] | UCLA SCTC GIT 2.0 (0.5 [0.2–1.0]) | 1389 (73) | GLIM | Malnutrition prevalence: 34% Malnutrition was associated with GI involvement, multimorbidity, cardiopulmonary disease, inflammation, hypoalbuminaemia, and anaemia |
[42] | 82 SSc | 49.4 ± 13.0 | UCLA SCTC GIT 2.0 (0.50 [0.04–1.49]) | 51 (62.2) | CONUT PNI | CONUT score: 1.45 ± 1.35 PNI: 43.59 ± 5.01 Malnutrition, as measured by CONUT and PNI, was associated with GI involvement |
3.5. Effects of the Nutritional Intervention on Gastrointestinal Involvement
Ref | Study Sample | Age (yrs) | Study Type (Years) | Nutritional Intervention Type | Nutritional Intervention Duration | Main Results |
---|---|---|---|---|---|---|
[17] | 66 SSc | 55.4 ± 11.8 | Prospective study (N/A) | Low-FODMAP | 10 days | Similar microbial composition and GI symptoms |
[43] | 80 SSc | Prospective observational study (2011–2014) | Low fructose diet | 1 month | Fructose malabsorption: 40% Correlation between fructose malabsorption and GSS score and absence of delayed gastric emptying Low-FODMAP: ↓ nausea, vomiting, abdominal pain, bloating, diarrhea, abdominal tenderness, and GSS score | |
32 Fructose malabsorption | 54 [27–79] | |||||
48 no-Fructose malaborption | 53 [22–79] | |||||
[44] | 42 SSc | 52 ± 12 | Prospective observational study (N/A) | Nutritional counseling | N/A | ↑> sodium intake Close association between dietary factors and body composition and GI symptoms. Malnutrition and weight loss were associated with pulmonary hypertension, heart failure, serum albumin, and skin fibrosis, but not advanced age |
[45] | 18 SSc | 51 ± 11 | Prospective study (N/A) | ON support | 6 week + usual medical therapy | ↓Nutrition symptom scores (12.8 vs. 7.6), and sarcopenia (54% vs. 39%) ↑ Appendicular lean height (5.6 ± 0.8 vs. 5.8 ± 0.8 kg/m2) No changes in caloric intake (1400 vs. 1577 kcal/d) and macronutrient distribution (% fat, protein, carbohydrate) |
[46] | 10+ SSc | 63 ± 12 | Prospective study (N/A) | Counselling + ON support | 12 months | Dietary intervention maintained body weight and food intake No change in nutritional biochemical parameters, psychopathology and quality of life |
[47] | 15 SSc | N/A | Retrospective study (1979–1987) | PN support | 2–90 months | ↑ Quality of life Complications: catheter-related septicaemia (13%), superior vena cava obstruction (13%). 46% dead, none directly from GI disease or from the PN |
[48] | 5 SSc | - | Cases Reports | PN (4 cases) and EN (1 case) support | PN: 12–86 months EN: 16 months | ↑ nutritional status, BMI, quality of life 60% dead from their disease |
[49] | 8 SSc | 51 [42–56] | Retrospective comparative study (1993–2006) | PN support | 40 [0.8–192] months | Complication: catheter-related infection (25%), line infection (25%), loss of autonomy (75%) |
[50] | 12 SSc | 49 ± 4 | Retrospective study (1998–2010) | HTPN support | 5–270 months | ↑ BMI: from 16.8 [12.3–21.3] kg/m2 to 18.3 [17.0–21.7] kg/m2 at 6 months and 19.7 [17.0-24.6] kg/m2 at 12 months No change in Karnofsky score (from 58.00 ± 3.27 to 39.00 ± 13.29 at 12 months) |
[51] | 25 SSc | 55 [24–79] | Retrospective study (1990–1992) | PN support | 3 months | Nutritional intervention duration: Mortality: 25% at 2-, 63% at 5-, and 77% at 10- years, but none directly from the PN Complication: catheter-related occlusion, sepsis, and thrombosis |
[52] | 5 SSc | 62.2 | Retrospective study (2008–2013) | PN support | 12 months | ↓Nutritional risk screening score (from 4.4 [4,5] to 1.4 [1,2] ↑BMI (from 19.1 [17.4–20.3] kg/m2 to 21.0 [18.3–23.4] kg/m2 ↑ Quality of life Complication: catheter-related infection (40%) |
3.6. Systemic Sclerosis and Predictors of Mortality
Ref | Sample Size | Age (yrs) | Follow up | Predictor factors of Mortality | Hazard Ratio (95% CI) | p-Value |
---|---|---|---|---|---|---|
[36] | 101 SSc | 55 [47–66] | 48 months | Malnutrition according GLIM criteria | 4.38 (1.70–11.24) | 0.002 |
[53] | 124 SSc | 54.0 ± 13.0 | 14.9 ± 6.7 months | Malnutrition | N/A | - |
295 HCs | 48.2 ± 11.8 | |||||
[54] | 160 SSc | 62 [54–68] | 46 months | Disease activity | 6.3 (1.8–21.7) | 0.004 |
MUST | 8.3 (2.1–32.1) | 0.002 | ||||
[55] | 299 SSc | 61 ± 11.8 | 48 [25–58] months | Low prealbumin | 3.00 (1.52–5.97) | 0.002 |
Lung involvement | 5.00 (2.45–10.34) | <0.001 | ||||
Multiple visceral organ involvement | 3.94 (2.01–7.74) | <0.001 | ||||
[56] | 349 SSc | 46.2 ± 4.1 | 2.1 years | Smoking | 4.0 (1.5–10.6) | ≤0.05 |
SSc-overlap | 6.0 (1.8–19.1) | ≤0.05 | ||||
Baseline renal involvement | 2.5 (2.2–11.7) | ≤0.05 | ||||
PAP ≥ 40 mmHg | 2.6 (1.1–6.5) | ≤0.05 | ||||
Peripheral vasculopathy therapy | 2.6 (1.1–6.5) | ≤0.05 | ||||
Parenteral nutrition | 8.8 (2.2–34.3) | ≤0.05 | ||||
[57] | 220 SSc | 51.16 ± 14.52 | 5.85 ± 4.10 years | Gener, male | 5.84 (1.31–26.00) | 0.020 |
Severe malnutrition | 3.77 (1.23–11.06) | 0.021 | ||||
Severe general symptoms | 5.12 (1.74–14-97) | 0.003 | ||||
[58] | 104 SSc | 55 [45–66] | 48 months | Bioelectrical impedence analysis-derived phase angle | 0.283 (0.083–0.965) | 0.044 |
4. Discussion
5. Future Perspectives and Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
SSc | Systemic Sclerosis |
HCs | Healthy Controls |
GM | Gut Microbiota |
GI | Gastrointestinal |
SIBO | Intestinal Bacterial Overgrowth |
VEDOSS | Very Early Diagnosis of Systemic Sclerosis |
ILD | Interstitial Lung Disease |
FMT | Fecal Microbiota Transplantation |
UCLA GIT 2.0 | University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 |
ONS | Oral Nutrition Support |
EN | Enteral Nutrition |
PN | Parenteral Nutrition |
MUST | Malnutrition Universal Screening Tool |
ESPEN | European Society of Clinical Nutrition and Metabolism |
GLIM | Global Leadership Initiative on Malnutrition |
SNAQ | Short Nutritional Assessment Questionnaire |
7-SGA | Subjective Global Assessment, 1–7 points |
RCTs | Randomized Controlled Trials |
SCFA | Short-Chain Fatty Acid |
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Gori, F.; Tomaino, L.; La Vecchia, C.; Servida, S.; Vigna, L. The Relationship Between Microbiota, Nutrition, and Gastrointestinal Tract Symptoms in Patients with Systemic Sclerosis: A Systematic Review of the Literature. Int. J. Mol. Sci. 2025, 26, 7685. https://doi.org/10.3390/ijms26167685
Gori F, Tomaino L, La Vecchia C, Servida S, Vigna L. The Relationship Between Microbiota, Nutrition, and Gastrointestinal Tract Symptoms in Patients with Systemic Sclerosis: A Systematic Review of the Literature. International Journal of Molecular Sciences. 2025; 26(16):7685. https://doi.org/10.3390/ijms26167685
Chicago/Turabian StyleGori, Francesca, Laura Tomaino, Carlo La Vecchia, Simona Servida, and Luisella Vigna. 2025. "The Relationship Between Microbiota, Nutrition, and Gastrointestinal Tract Symptoms in Patients with Systemic Sclerosis: A Systematic Review of the Literature" International Journal of Molecular Sciences 26, no. 16: 7685. https://doi.org/10.3390/ijms26167685
APA StyleGori, F., Tomaino, L., La Vecchia, C., Servida, S., & Vigna, L. (2025). The Relationship Between Microbiota, Nutrition, and Gastrointestinal Tract Symptoms in Patients with Systemic Sclerosis: A Systematic Review of the Literature. International Journal of Molecular Sciences, 26(16), 7685. https://doi.org/10.3390/ijms26167685