Gut bacteria and health have been topics of considerable scientific speculation in recent years, and the field of multiple sclerosis (MS) research is no exception. But what do we really know about MS and our intestinal inhabitants?
A review, “Emerging Concepts on the Gut Microbiome and Multiple Sclerosis,” published in the Journal Of Interferon & Cytokine Research by two Johns Hopkins University School of Medicine researchers, offers a detailed overview, while noting plenty of room exists for more research into how gut bacteria might be manipulated to benefit MS patients.
Despite a widespread fear of bacteria — likely fueled by the development and marketing of products that promise to keep our homes and ourselves 99.9% germ-free — bacteria are as indispensable to our health as our cells.
Studies in the last decades increasingly show that gut bacteria influence our immune system, and indications abound that an imbalanced gut flora — often called microbiota or microbiome (which really refers to the collective genome of all our gut bacteria) — is involved in autoimmune conditions.
Interactions between gut bacteria and the immune system go both ways. Studies of germ-free mice show that without bacteria, normal immune system development is disrupted. But bacteria come in a variety of types and shapes, not all of which are good.
Broadly, bacteria can be divided into those that suppress our immune system and those who trigger inflammation, but on a species level they can differ as to the types of molecular responses they elicit. On this particular topic there is plenty of research, showing how individual bacteria affect immune components ranging from cells, over signaling factors such as cytokines, to the induction of changes in immune gene activity. Bacteria also share the interstitial space with viruses, at times equally necessary for our normal immune functions.
The composition of bacterial types and species can be affected by a range of factors, including our diet. Lean and obese individuals differ in what types of bacteria reside in their guts, and a ‘Western diet’ — based on proteins, animal fat, refined carbohydrates, and a large sugar intake — is particularly linked to more inflammatory gut processes.
The type of fat we eat has been shown to activate various populations of immune T-cells, with so-called short-chain fatty acids promoting activation of regulatory T-cells, or Tregs — guardians against excessive inflammation — and long-chain fatty acids triggering the formation of inflammatory T-cell types.
Given that germ-free mice, as mentioned earlier, do not develop a normal immune system, it was not surprising to find that it was not possible to trigger ‘MS,’ or experimental autoimmune encephalomyelitis (EAE), in these animals. After all, this mouse model of MS relies on autoimmune processes. When such mice were colonized with bacteria, the development of inflammatory T-cells in the gut soon followed, as did EAE.
Experiments have also shown that antibiotic treatment makes it more difficult to trigger this MS-like disease in mice. Other studies have been more specific, showing that the actions of specific bacteria protect mice from the autoimmune disease. Researchers have also experimented by giving MS mice a cocktail of ‘good bacteria,’ showing that it indeed improved the disease and shifted immune responses to a more beneficial type.
Such experiments highlight the likelihood that an imbalance, or dysbiosis as it is called in scientific language, in gut bacterial composition might contribute to the development of MS. This idea is supported by several studies exploring the bacterial composition in MS patients, with the latest addition published earlier this month.
Children delivered by cesarean section are known to have severely delayed bacterial colonization, and a higher risk of developing MS. This might seem contradictory considering the mouse experiments, but research clearly shows that when normal bacterial colonization (from vaginal and fecal bacteria during birth, or bacteria ingested during breast-feeding) is prevented, other, less friendly, bacterial species move in, increasing the risk for disease. In fact, studies show that MS patients have often been breastfed for shorter periods than people free of the disease.
Going back to studies of MS patients’ guts, researchers typically find that patients have a greater variability in their bacterial species than healthy people. Certain types were more often affected, with several studies reporting lower numbers of Bacteroides, Faecalibacterium, Prevotella, and Anaerostipes, while Bifidobacterium and Streptococcus were found in higher numbers.
Indications that bacterial toxins might be involved in MS development have also emerged, but this hypothesis is not yet well-investigated.
Since evidence of the two links — between gut bacteria and our immune system, and between an imbalance in gut bacteria and MS — started to mount, researchers have turned their gaze to interventions targeting the gut, hoping to find new ways to harness a disease that has proven difficult to master.
Several such studies are in clinical trials. Vitamin D is thought to be beneficial for MS patients, and some trials show that it lowers the risk of relapses and new brain lesions. With a known role for the vitamin in the workings of the immune system, it is not surprising to find that patients on vitamin D treatments had lower levels of inflammatory T-cells and other immune mediators. There are also some indications that vitamin D has direct effects on the bacterial composition in the gut.
Another intervention, with a better known link to the gut, is probiotics — the addition of good bacteria through supplements. Probiotics are already extensively used in patients with inflammatory gut conditions, but experiments in MS mouse models have produced mixed results. Probiotic use also has not been investigated in MS patients.
But future trials have a number of issues to consider. Just adding a bacterial species to an environment already inhabited by millions of others does not guarantee that it will survive. Bacteria use several mechanisms to kill each other in the fight for space and nutrients. For example, many bacteria live in symbiosis with viruses that infect and kill their unwanted neighbors. To improve the chances of added bacteria surviving, probiotic supplements might need to be tailored to the specific imbalance present in each patient.
Another trick scientists are considering is making use of viruses, by giving bacteria virus combinations that can easier compete with disease-causing species. A Phase 2 clinical trial of such a virus, used against a bacteria that has developed resistance to most antibiotics, has shown promising results.
As mentioned earlier, diet is also key to keeping the gut healthy, as many of the inflammation-causing species require nutrients typically present in a Western diet.
The idea that MS can be tackled by controlling our gut inhabitants is, nevertheless, rather new, and plenty of research is needed to show exactly if, and how, this might be made possible.