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ORLANDO—Probiotic treatment is associated with the induction of an anti-inflammatory peripheral immune profile in patients with multiple sclerosis (MS), and discontinuing probiotics is associated with a decrease in immune regulatory cells, according to pilot study results presented at the ACTRIMS 2017 Forum. The results suggest that probiotics may be applicable as a therapy for MS. More studies, including controlled clinical trials, are needed to guide treatment decisions, said Howard L. Weiner, MD, Director of the MS Program at Brigham and Women’s Hospital in Newton, Massachusetts, and Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston. 
The gut microbiome can modulate neuroimmune function, and studies have found that patients with MS have alterations in the gut microbiome, compared with healthy controls. These findings have led researchers to ask, “Can you treat MS by modulating the microbiome?” Dr. Weiner said. One way to modulate the microbiome is with probiotics, which can be taken as an oral, nontoxic treatment in combination with current therapies. He and his research colleagues conducted a pilot study to investigate the effect of probiotics in patients with MS. “We did not feel that we could do a clinically related study,” he said. Instead, the investigators focused on what happens to the gut microbiome and immune profiles in the blood of patients who receive probiotics.
Two Months of Treatment
The study included nine patients with MS and 13 controls. The investigators gave study participants the probiotic VSL#3. Some formulations of VSL#3 are available in stores. The company that markets the probiotic, Sigma-Tau HealthScience USA, based in Gaithersburg, Maryland, requires a prescription for VSL#3 DS, the double-strength formulation used in the study.
Prior studies of the probiotic have found that VSL#3 provides benefit in animal models of diabetes, colitis, and allergy. Kigerl et al reported that, in mice with spinal cord injury, dysbiosis induced by antibiotics exacerbates neurologic impairment and spinal cord pathology, whereas feeding mice VSL#3 enriched with lactic-acid-producing bacteria triggers a protective immune response, confers neuroprotection, and improves walking. In addition, some doctors prescribe VSL#3 to patients with ulcerative colitis, irritable bowel syndrome, and pouchitis, Dr. Weiner said.
In the pilot study, participants took VSL#3 DS sachets twice daily for two months. Researchers took blood and stool samples from participants before administering the probiotic, at discontinuation of therapy, and three months thereafter.
VSL#3 had no effect on alpha or phylogenetic diversity, but did change the gut microbiome composition. Researchers observed an increase in the relative abundance of specific organisms contained in the probiotic. Methanogens, which are increased in MS, decreased when patients received the probiotic. Administration of VSL#3 also was associated with a decrease in proinflammatory monocytes and decreased expression of activation markers on monocytes and dendritic cells.
When patients stopped probiotic treatment, the numbers of CD39 and IL10 T regulatory cells decreased, and proinflammatory monocytes increased. “We did see changes when you stop treatment, almost as if there is a rebound,” he said. “We are seeing an immune effect in the blood.”
The treatment was well tolerated. “I myself took some,” Dr. Weiner said. “It tastes a little chalky, but otherwise it is fine.” Some patients said they felt better after taking the probiotic. The study was not placebo-controlled, however. Future randomized clinical studies will include MRI scans, he said.
What should neurologists tell patients who want to take a probiotic and ask which probiotic they should take? “We are all asked those questions,” Dr. Weiner said. “I tell them, we really don’t know, but if you would like to take a probiotic, that is fine. But we have no particular recommendations at this time. We need a lot of science before we know what we are doing, as far as treatment, in this regard.”
Changes in the Gut Microbiome in MS
Prior to conducting the pilot study, Sushrut Jangi, MD, research fellow at Brigham and Women’s Hospital, Dr. Weiner, and colleagues studied the gut microbiome in 60 patients with MS and 43 healthy controls. They found that patients with MS had increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, compared with controls. Methanobrevibacter produces methane, and in another cohort, the researchers detected more methane in the breath of patients with MS than in controls.
In addition, Prevotella and Sutterella were increased, and Sarcina was decreased in patients with MS who were treated with disease-modifying therapy, compared with untreated patients with MS. “It gives us a whole series of targets to try to understand,” he said. The gut microbiome alterations in patients with MS correlated with variations in the expression of genes in circulating T cells and monocytes that have been implicated in MS pathogenesis.
How Are the Gut Microbiome and MS Related?
The nature of the relationship between the gut microbiome and MS is unclear. One possibility is that “the gut could be the key to MS,” Dr. Weiner said. An organism in the gut may trigger MS, and that organism potentially could be altered or used in vaccinations to treat or prevent the disease. Alternatively, the gut microbiome might relate to MS susceptibility. Environmental factors, including diet and antibiotics, could affect the microbiome and MS risk. It is also possible that MS disease-modifying therapies act in part through the gut, Dr. Weiner said.
Various treatments targeting the microbiome are under investigation. For example, researchers are asking whether a particular bacteria or fecal microbiome transplants might help treat MS. “I am very interested in the concept of oral tolerance, where we trigger immune responses in the mucosa,” said Dr. Weiner. “We are beginning a trial of anti-CD3 [monoclonal antibodies], which will be given mucosally to stimulate the gut immune response.”
—Jake Remaly
Suggested Reading
Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015.
Kigerl KA, Hall JC, Wang L, et al. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med. 2016;213(12):2603-2620.
Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2016 Sep 16 [Epub ahead of print].
Miyake S, Kim S, Suda W, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015;10(9):e0137429.
Tremlett H, Waubant E. The multiple sclerosis microbiome? Ann Transl Med. 2017;5(3):53.
ORLANDO—Probiotic treatment is associated with the induction of an anti-inflammatory peripheral immune profile in patients with multiple sclerosis (MS), and discontinuing probiotics is associated with a decrease in immune regulatory cells, according to pilot study results presented at the ACTRIMS 2017 Forum. The results suggest that probiotics may be applicable as a therapy for MS. More studies, including controlled clinical trials, are needed to guide treatment decisions, said Howard L. Weiner, MD, Director of the MS Program at Brigham and Women’s Hospital in Newton, Massachusetts, and Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston.
The gut microbiome can modulate neuroimmune function, and studies have found that patients with MS have alterations in the gut microbiome, compared with healthy controls. These findings have led researchers to ask, “Can you treat MS by modulating the microbiome?” Dr. Weiner said. One way to modulate the microbiome is with probiotics, which can be taken as an oral, nontoxic treatment in combination with current therapies. He and his research colleagues conducted a pilot study to investigate the effect of probiotics in patients with MS. “We did not feel that we could do a clinically related study,” he said. Instead, the investigators focused on what happens to the gut microbiome and immune profiles in the blood of patients who receive probiotics.
Two Months of Treatment
The study included nine patients with MS and 13 controls. The investigators gave study participants the probiotic VSL#3. Some formulations of VSL#3 are available in stores. The company that markets the probiotic, Sigma-Tau HealthScience USA, based in Gaithersburg, Maryland, requires a prescription for VSL#3 DS, the double-strength formulation used in the study.
Prior studies of the probiotic have found that VSL#3 provides benefit in animal models of diabetes, colitis, and allergy. Kigerl et al reported that, in mice with spinal cord injury, dysbiosis induced by antibiotics exacerbates neurologic impairment and spinal cord pathology, whereas feeding mice VSL#3 enriched with lactic-acid-producing bacteria triggers a protective immune response, confers neuroprotection, and improves walking. In addition, some doctors prescribe VSL#3 to patients with ulcerative colitis, irritable bowel syndrome, and pouchitis, Dr. Weiner said.
In the pilot study, participants took VSL#3 DS sachets twice daily for two months. Researchers took blood and stool samples from participants before administering the probiotic, at discontinuation of therapy, and three months thereafter.
VSL#3 had no effect on alpha or phylogenetic diversity, but did change the gut microbiome composition. Researchers observed an increase in the relative abundance of specific organisms contained in the probiotic. Methanogens, which are increased in MS, decreased when patients received the probiotic. Administration of VSL#3 also was associated with a decrease in proinflammatory monocytes and decreased expression of activation markers on monocytes and dendritic cells.
When patients stopped probiotic treatment, the numbers of CD39 and IL10 T regulatory cells decreased, and proinflammatory monocytes increased. “We did see changes when you stop treatment, almost as if there is a rebound,” he said. “We are seeing an immune effect in the blood.”
The treatment was well tolerated. “I myself took some,” Dr. Weiner said. “It tastes a little chalky, but otherwise it is fine.” Some patients said they felt better after taking the probiotic. The study was not placebo-controlled, however. Future randomized clinical studies will include MRI scans, he said.
What should neurologists tell patients who want to take a probiotic and ask which probiotic they should take? “We are all asked those questions,” Dr. Weiner said. “I tell them, we really don’t know, but if you would like to take a probiotic, that is fine. But we have no particular recommendations at this time. We need a lot of science before we know what we are doing, as far as treatment, in this regard.”
Changes in the Gut Microbiome in MS
Prior to conducting the pilot study, Sushrut Jangi, MD, research fellow at Brigham and Women’s Hospital, Dr. Weiner, and colleagues studied the gut microbiome in 60 patients with MS and 43 healthy controls. They found that patients with MS had increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, compared with controls. Methanobrevibacter produces methane, and in another cohort, the researchers detected more methane in the breath of patients with MS than in controls.
In addition, Prevotella and Sutterella were increased, and Sarcina was decreased in patients with MS who were treated with disease-modifying therapy, compared with untreated patients with MS. “It gives us a whole series of targets to try to understand,” he said. The gut microbiome alterations in patients with MS correlated with variations in the expression of genes in circulating T cells and monocytes that have been implicated in MS pathogenesis.
How Are the Gut Microbiome and MS Related?
The nature of the relationship between the gut microbiome and MS is unclear. One possibility is that “the gut could be the key to MS,” Dr. Weiner said. An organism in the gut may trigger MS, and that organism potentially could be altered or used in vaccinations to treat or prevent the disease. Alternatively, the gut microbiome might relate to MS susceptibility. Environmental factors, including diet and antibiotics, could affect the microbiome and MS risk. It is also possible that MS disease-modifying therapies act in part through the gut, Dr. Weiner said.
Various treatments targeting the microbiome are under investigation. For example, researchers are asking whether a particular bacteria or fecal microbiome transplants might help treat MS. “I am very interested in the concept of oral tolerance, where we trigger immune responses in the mucosa,” said Dr. Weiner. “We are beginning a trial of anti-CD3 [monoclonal antibodies], which will be given mucosally to stimulate the gut immune response.”
—Jake Remaly
Suggested Reading
Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015.
Kigerl KA, Hall JC, Wang L, et al. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med. 2016;213(12):2603-2620.
Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2016 Sep 16 [Epub ahead of print].
Miyake S, Kim S, Suda W, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015;10(9):e0137429.
Tremlett H, Waubant E. The multiple sclerosis microbiome? Ann Transl Med. 2017;5(3):53.
ORLANDO—Probiotic treatment is associated with the induction of an anti-inflammatory peripheral immune profile in patients with multiple sclerosis (MS), and discontinuing probiotics is associated with a decrease in immune regulatory cells, according to pilot study results presented at the ACTRIMS 2017 Forum. The results suggest that probiotics may be applicable as a therapy for MS. More studies, including controlled clinical trials, are needed to guide treatment decisions, said Howard L. Weiner, MD, Director of the MS Program at Brigham and Women’s Hospital in Newton, Massachusetts, and Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston.
The gut microbiome can modulate neuroimmune function, and studies have found that patients with MS have alterations in the gut microbiome, compared with healthy controls. These findings have led researchers to ask, “Can you treat MS by modulating the microbiome?” Dr. Weiner said. One way to modulate the microbiome is with probiotics, which can be taken as an oral, nontoxic treatment in combination with current therapies. He and his research colleagues conducted a pilot study to investigate the effect of probiotics in patients with MS. “We did not feel that we could do a clinically related study,” he said. Instead, the investigators focused on what happens to the gut microbiome and immune profiles in the blood of patients who receive probiotics.
Two Months of Treatment
The study included nine patients with MS and 13 controls. The investigators gave study participants the probiotic VSL#3. Some formulations of VSL#3 are available in stores. The company that markets the probiotic, Sigma-Tau HealthScience USA, based in Gaithersburg, Maryland, requires a prescription for VSL#3 DS, the double-strength formulation used in the study.
Prior studies of the probiotic have found that VSL#3 provides benefit in animal models of diabetes, colitis, and allergy. Kigerl et al reported that, in mice with spinal cord injury, dysbiosis induced by antibiotics exacerbates neurologic impairment and spinal cord pathology, whereas feeding mice VSL#3 enriched with lactic-acid-producing bacteria triggers a protective immune response, confers neuroprotection, and improves walking. In addition, some doctors prescribe VSL#3 to patients with ulcerative colitis, irritable bowel syndrome, and pouchitis, Dr. Weiner said.
In the pilot study, participants took VSL#3 DS sachets twice daily for two months. Researchers took blood and stool samples from participants before administering the probiotic, at discontinuation of therapy, and three months thereafter.
VSL#3 had no effect on alpha or phylogenetic diversity, but did change the gut microbiome composition. Researchers observed an increase in the relative abundance of specific organisms contained in the probiotic. Methanogens, which are increased in MS, decreased when patients received the probiotic. Administration of VSL#3 also was associated with a decrease in proinflammatory monocytes and decreased expression of activation markers on monocytes and dendritic cells.
When patients stopped probiotic treatment, the numbers of CD39 and IL10 T regulatory cells decreased, and proinflammatory monocytes increased. “We did see changes when you stop treatment, almost as if there is a rebound,” he said. “We are seeing an immune effect in the blood.”
The treatment was well tolerated. “I myself took some,” Dr. Weiner said. “It tastes a little chalky, but otherwise it is fine.” Some patients said they felt better after taking the probiotic. The study was not placebo-controlled, however. Future randomized clinical studies will include MRI scans, he said.
What should neurologists tell patients who want to take a probiotic and ask which probiotic they should take? “We are all asked those questions,” Dr. Weiner said. “I tell them, we really don’t know, but if you would like to take a probiotic, that is fine. But we have no particular recommendations at this time. We need a lot of science before we know what we are doing, as far as treatment, in this regard.”
Changes in the Gut Microbiome in MS
Prior to conducting the pilot study, Sushrut Jangi, MD, research fellow at Brigham and Women’s Hospital, Dr. Weiner, and colleagues studied the gut microbiome in 60 patients with MS and 43 healthy controls. They found that patients with MS had increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, compared with controls. Methanobrevibacter produces methane, and in another cohort, the researchers detected more methane in the breath of patients with MS than in controls.
In addition, Prevotella and Sutterella were increased, and Sarcina was decreased in patients with MS who were treated with disease-modifying therapy, compared with untreated patients with MS. “It gives us a whole series of targets to try to understand,” he said. The gut microbiome alterations in patients with MS correlated with variations in the expression of genes in circulating T cells and monocytes that have been implicated in MS pathogenesis.
How Are the Gut Microbiome and MS Related?
The nature of the relationship between the gut microbiome and MS is unclear. One possibility is that “the gut could be the key to MS,” Dr. Weiner said. An organism in the gut may trigger MS, and that organism potentially could be altered or used in vaccinations to treat or prevent the disease. Alternatively, the gut microbiome might relate to MS susceptibility. Environmental factors, including diet and antibiotics, could affect the microbiome and MS risk. It is also possible that MS disease-modifying therapies act in part through the gut, Dr. Weiner said.
Various treatments targeting the microbiome are under investigation. For example, researchers are asking whether a particular bacteria or fecal microbiome transplants might help treat MS. “I am very interested in the concept of oral tolerance, where we trigger immune responses in the mucosa,” said Dr. Weiner. “We are beginning a trial of anti-CD3 [monoclonal antibodies], which will be given mucosally to stimulate the gut immune response.”
—Jake Remaly
Suggested Reading
Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015.
Kigerl KA, Hall JC, Wang L, et al. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med. 2016;213(12):2603-2620.
Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2016 Sep 16 [Epub ahead of print].
Miyake S, Kim S, Suda W, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015;10(9):e0137429.
Tremlett H, Waubant E. The multiple sclerosis microbiome? Ann Transl Med. 2017;5(3):53.