Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions

Abstract

This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT—though a limited number of studies was included—indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients’ emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.

Effect of Probiotic and Synbiotic Oral Supplementation in Autoimmune Diseases: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…The authors concluded that the most promising probiotics were formulations containing Lactobacillus paracasei , Bifidobacterium animalis , E. coli Nissle 1917, and Prevotella histicola . Tsogka et al [ 60 ] reviewed 13 studies published between 2011 and 2023, and found that a probiotic mixture showed promising results on MS-related fatigue, Expanded Disability Status Scale parameters, and inflammation. Overall, the authors concluded that probiotics promote a shift in inflammation towards an anti-inflammatory cytokine profile, as well as improving disability, mood, and quality of life.…”

Effect of Probiotic and Synbiotic Oral Supplementation in Autoimmune Diseases: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…The authors concluded that the most promising probiotics were formulations containing Lactobacillus paracasei , Bifidobacterium animalis , E. coli Nissle 1917, and Prevotella histicola . Tsogka et al [ 60 ] reviewed 13 studies published between 2011 and 2023, and found that a probiotic mixture showed promising results on MS-related fatigue, Expanded Disability Status Scale parameters, and inflammation. Overall, the authors concluded that probiotics promote a shift in inflammation towards an anti-inflammatory cytokine profile, as well as improving disability, mood, and quality of life.…”

Modulating the Gut Microbiome as a Therapeutic Approach in Multiple Sclerosis: Implications for Gut‐Brain Interactions and Immune Pathways: A Narrative Review

“…( 2017 ) demonstrated that fecal microbiota from MS patients induced a pro‐inflammatory phenotype following transplantation into germ‐free mice, providing causative evidence that MS‐associated human microbial communities modulate host immunity (Lin et al., 2024 ). Recent systematic reviews and meta‐analyses that integrated data across multiple MS cohorts consistently show depletion of SCFAs‐producing Clostridiales , Prevotella , and Faecalibacterium , with increased Akkermansia and Methanobrevibacter , reinforcing the reproducibility of these microbial signatures in humans (Tsogka et al., 2023 ; Rumah et al., 2013 ).…”

“…Smaller but functionally important proportions of Actinobacteria and Proteobacteria are also consistently present. These phylum‐level patterns provide the ecological framework for understanding dysbiosis, as shifts in the relative abundance of these groups form the basis of many microbiome alterations described in autoimmune and neuroinflammatory conditions, including MS (Tsogka et al., 2023 ; Hasaniani et al., 2024 ; Zhu et al., 2021 ).…”

“…These include conventional strategies such as probiotics, dietary modifications, IF, and FMT, each with varying levels of clinical validation. In a comprehensive systematic review, Tsogka et al ( 2023 ) evaluated 13 studies involving 212 relapsingremitting MS patients and 200 healthy controls. Their review encompassed interventions such as probiotic formulations like VSL#3 and LBS (a blend of Lactobacillus, Bifidobacterium, and Streptococcus), as well as dietary protocols, IF regimens, and case-based reports on FMT.…”

The role of the “gut microbiota-mitochondria” crosstalk in the pathogenesis of multiple sclerosis

“…In this review, we emphasize the potential mechanisms of gut microbiota and mitochondrial crosstalk in MS progression. To date, several therapeutic strategies, including probiotics, dietary interventions, fecal transplants, and administration of medications, have been used to slow MS progression ( Tsogka et al, 2023 ).…”

Effect of Probiotic and Synbiotic Oral Supplementation in Autoimmune Diseases: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…The authors concluded that the most promising probiotics were formulations containing Lactobacillus paracasei , Bifidobacterium animalis , E. coli Nissle 1917, and Prevotella histicola . Tsogka et al [ 60 ] reviewed 13 studies published between 2011 and 2023, and found that a probiotic mixture showed promising results on MS-related fatigue, Expanded Disability Status Scale parameters, and inflammation. Overall, the authors concluded that probiotics promote a shift in inflammation towards an anti-inflammatory cytokine profile, as well as improving disability, mood, and quality of life.…”

Modulating the Gut Microbiome as a Therapeutic Approach in Multiple Sclerosis: Implications for Gut‐Brain Interactions and Immune Pathways: A Narrative Review

“…( 2017 ) demonstrated that fecal microbiota from MS patients induced a pro‐inflammatory phenotype following transplantation into germ‐free mice, providing causative evidence that MS‐associated human microbial communities modulate host immunity (Lin et al., 2024 ). Recent systematic reviews and meta‐analyses that integrated data across multiple MS cohorts consistently show depletion of SCFAs‐producing Clostridiales , Prevotella , and Faecalibacterium , with increased Akkermansia and Methanobrevibacter , reinforcing the reproducibility of these microbial signatures in humans (Tsogka et al., 2023 ; Rumah et al., 2013 ).…”

“…Smaller but functionally important proportions of Actinobacteria and Proteobacteria are also consistently present. These phylum‐level patterns provide the ecological framework for understanding dysbiosis, as shifts in the relative abundance of these groups form the basis of many microbiome alterations described in autoimmune and neuroinflammatory conditions, including MS (Tsogka et al., 2023 ; Hasaniani et al., 2024 ; Zhu et al., 2021 ).…”

“…These include conventional strategies such as probiotics, dietary modifications, IF, and FMT, each with varying levels of clinical validation. In a comprehensive systematic review, Tsogka et al ( 2023 ) evaluated 13 studies involving 212 relapsingremitting MS patients and 200 healthy controls. Their review encompassed interventions such as probiotic formulations like VSL#3 and LBS (a blend of Lactobacillus, Bifidobacterium, and Streptococcus), as well as dietary protocols, IF regimens, and case-based reports on FMT.…”

The role of the “gut microbiota-mitochondria” crosstalk in the pathogenesis of multiple sclerosis

“…In this review, we emphasize the potential mechanisms of gut microbiota and mitochondrial crosstalk in MS progression. To date, several therapeutic strategies, including probiotics, dietary interventions, fecal transplants, and administration of medications, have been used to slow MS progression ( Tsogka et al, 2023 ).…”

Effect of Probiotic and Synbiotic Oral Supplementation in Autoimmune Diseases: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…The authors concluded that the most promising probiotics were formulations containing Lactobacillus paracasei , Bifidobacterium animalis , E. coli Nissle 1917, and Prevotella histicola . Tsogka et al [ 60 ] reviewed 13 studies published between 2011 and 2023, and found that a probiotic mixture showed promising results on MS-related fatigue, Expanded Disability Status Scale parameters, and inflammation. Overall, the authors concluded that probiotics promote a shift in inflammation towards an anti-inflammatory cytokine profile, as well as improving disability, mood, and quality of life.…”

Modulating the Gut Microbiome as a Therapeutic Approach in Multiple Sclerosis: Implications for Gut‐Brain Interactions and Immune Pathways: A Narrative Review

“…( 2017 ) demonstrated that fecal microbiota from MS patients induced a pro‐inflammatory phenotype following transplantation into germ‐free mice, providing causative evidence that MS‐associated human microbial communities modulate host immunity (Lin et al., 2024 ). Recent systematic reviews and meta‐analyses that integrated data across multiple MS cohorts consistently show depletion of SCFAs‐producing Clostridiales , Prevotella , and Faecalibacterium , with increased Akkermansia and Methanobrevibacter , reinforcing the reproducibility of these microbial signatures in humans (Tsogka et al., 2023 ; Rumah et al., 2013 ).…”

“…Smaller but functionally important proportions of Actinobacteria and Proteobacteria are also consistently present. These phylum‐level patterns provide the ecological framework for understanding dysbiosis, as shifts in the relative abundance of these groups form the basis of many microbiome alterations described in autoimmune and neuroinflammatory conditions, including MS (Tsogka et al., 2023 ; Hasaniani et al., 2024 ; Zhu et al., 2021 ).…”

“…These include conventional strategies such as probiotics, dietary modifications, IF, and FMT, each with varying levels of clinical validation. In a comprehensive systematic review, Tsogka et al ( 2023 ) evaluated 13 studies involving 212 relapsingremitting MS patients and 200 healthy controls. Their review encompassed interventions such as probiotic formulations like VSL#3 and LBS (a blend of Lactobacillus, Bifidobacterium, and Streptococcus), as well as dietary protocols, IF regimens, and case-based reports on FMT.…”

The role of the “gut microbiota-mitochondria” crosstalk in the pathogenesis of multiple sclerosis

“…In this review, we emphasize the potential mechanisms of gut microbiota and mitochondrial crosstalk in MS progression. To date, several therapeutic strategies, including probiotics, dietary interventions, fecal transplants, and administration of medications, have been used to slow MS progression ( Tsogka et al, 2023 ).…”