Probiotic Supplementation in Pregnancy Reduces the Risk of Anxiety and Depression

Though the evidence of the role of diet and the gut in the development of psychological disorders is established and growing, the majority of the research has either been epidemiological (observations of large groups of people – these do not show causality) or animals trials (show the mechanisms but might not completely translate to humans). At the end of all of these papers the authors remark that more high-quality human trials are required to draw firmer conclusions. Earlier in the year we had the publication of the SMILES Trial, a study that showed a cause and effect relationship between poor diet and depression and now a new paper provides more good evidence of the role of probiotics and the gut microbiome on mental health. Even more interesting is that this was not even the main aim of the research.

Researchers in New Zealand set up a trial to see whether giving pregnant women probiotics would affect their children’s risk of developing eczema. Eczema is an inflammatory skin condition and the gut microbiome plays an essential role in regulating inflammation. A baby’s gut microbiome is seeded at birth during its transit through the birth canal, or from skin contact after delivery by caesarean section. In the study 423 pregnant women were randomly assigned to two groups. One group received a daily supplement of a strain of bacteria called Lactobacillus rhamnosus (HN001). The other group received an identical looking/tasting placebo. The women took the supplement/placebo from the moment they enrolled until their child was born, and from birth until 6 months if the mother was breastfeeding. Information about the women’s mental state was taken at baseline (14-16 weeks pregnant), when the child was 6 months and 12 months old. They found a strong effect of the probiotic. The women who had taken the supplement (and none of the women knew whether they were taking the active supplement or the placebo) were much less likely to experience depression and anxiety after the birth of their children.  

The researchers report that between 10%-15% of women experience post-partum (post-natal) depression, which can impair the development of a strong bond between mother and infant, creating psychological and physical health risks for both. Medication options for breastfeeding women are limited because of the risk that the medication would be ingested by the baby in breast milk. In addition, it is practically difficult for women to access psychological or psychosocial interventions on top of the demands of a new baby. Further, some women feel reluctant to ask for help because they feel ashamed or guilty that they should feel so unhappy following the birth of their baby. Clearly then, the development of accessible and effective treatments is essential. There are many questions still to be answered about what a probiotic treatment might look like. This trial looked at only one strain and it might be that others of a combination are important too. We also need to know how long treatment should last and what the dose should be. But this well-designed study adds to the evidence of the role and importance of gut health in mental health and of taking the health of the whole body in to consideration when looking to treat mental health problems.

Reference

Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial. DOI: 10.1016/j.ebiom.2017.09.013

Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review

Many by now will be familiar with the term ‘friendly bacteria’, referring to the vast population of bacteria in the digestive tract. This population of microbes (the microbiome) play an important role in maintaining our digestive health and many people consume yogurt and other fermented milk drinks to promote gut health. Increasingly research is showing us that the gut microbiome has a significant effect on our mental as well as physical health.

To gain a better overview of the current status of research in this area a systemic review of random controlled trials was conducted and published in the Journal of Neurogastroenterology & Motility. The researchers reviewed 25 animal and 15 human trials. Of the studies involving human participants just over half described significant effects of probiotics on central nervous system function and an intake of probiotics for four weeks appeared to be the threshold for noticeable effects. In the human trials the most common bacterial strains tested were Bifidobacterium longum, B. breve, B. infantis, Lactobacillus helveticus, L. rhamnosus, L. plantarum, and L. casei, all of which are present in fermented foods such as yogurt, kefir and traditional (unpasteurised) sauerkraut.

Looking at both the animal models and human trials the results of this review indicated that probiotics were an effective intervention for a range of mental health disorders including anxiety, depression, Obsessive Compulsive Disorder (OCD) and memory function. A number of potential mechanisms were identified:

• Reduced cortisol (stress hormone) levels

• Reduced inflammation.

• Improved immune function

It is also feasible that some of the known metabolites of the microbiome such as GABA, an inhibitory neurotransmitter, might play a role either via the vagus nerve or more directly by crossing the blood-brain barrier. Whilst the review is generally positive the researchers called for further studies to be conducted with human participants in order to be able to draw firmer conclusions on the promising role of probiotics on mental diseases.

Reference:

Wang, H., Lee, I., Braun, C. & Enck, P. (2016). Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review. Journal of Neurogastroenterology & Motility, 22, 589-605.

Chronic Fatigue in Your Gut Not Your Head

In April I reported a study demonstrating that probiotic supplementation had a beneficial effect on one of the psychological symptoms of Chronic Fatigue Syndrome (CFS). In that 2009 paper patients on the treatment for eight weeks were significantly less anxious than those taking the placebo product. Published in June this year a new study builds on that observation. The researchers at Cornell University first noted the frequent comorbidity of gastro-intestinal disorders with CFS, as well as evidence of abnormal immune response in individuals with CFS as indicated by markers of inflammation in the blood. They hypothesised that, taken together, gut microbiome diversity and levels of inflammation could predict who had a diagnosis of CFS.

This study compared the samples of 39 healthy people and 49 individuals with CFS. By looking at differences in the samples the researchers were able to identify disease cases with 83% accuracy. They found that those with CFS were significantly more likely to show signs of microbial translocation, where bacteria that reside in the gut break through the gut wall and enter the blood stream. Since they should not be present in this part of the body the immune system recognises these roving bacteria as intruders and launches an immune (inflammatory) response. This inflammation is associated with many of the symptoms of illness in CFS and other infections.

Compared to the samples of healthy individuals ME patients had reduced numbers and diversity of a type of bacteria called Firmicutes¸ typically the most abundant phyla in the human gut microbiome, as well as significantly lower amounts of types associated with an anti-inflammatory affect.

In the long-running debate about what causes Chronic Fatigue Syndrome the arguments tend to fall dichotomously: it’s either psychological OR biological in nature. Some research has shown a positive effect of psychotherapy in alleviating symptoms whilst others have found improvement with microbiome modification. The likelihood is, therefore, that a combined treatment approach will yield the best results for patients, helping them to manage both the physical and psychological symptoms of this debilitating disease. 

Giloteaux, L., Goodrich, J. K., Walters, W. A., Levine, S. M., Ley, R. E. & Hanson, M. R. (2016). Reduces diversity and altered composition of the gut microbiome in individuals with myalgic encephalomeylitis/chronic fatigue syndrome. Microbiome, 4:30.

Jason, L. A., Torres-Harding, S. Friedberg, F., Corradi, K., Njoku, M. G., Donalek., J., Reynolds, N., Brown, M., Weitner, B. B., Rademaker, A. & Papernik, M. (2007). Non-pharmalogical interventions for CFS: A randomized trial. Journal of Clinical Psychology in Medical Settings, 14, 275-296.

Borody, T. J., Nowak, A & Finlayson, S. (2012). The GI mircobiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy. Journal of the Australasian College of Nutritional and Environmental Medicine, 31, 3-8.

Dietary Fibre Linked with Improved Cognitive Control in Children

A correlation study conducted with small group of 7 and 9 year olds demonstrated a positive relationship between diet quality, in particular dietary fibre content, and performance on a task designed to assess attention and the ability to disregard distracting stimuli.

65 children undertook a modified version of the Erikson Flanker Test in which they were asked to pay attention to the direction of a fish in the centre of a computer screen and to try to ignore other fish that appeared on the screen at the same time that were facing either the same direction or the opposite direction of the target fish. Their results were correlated against food diaries that tracked a range of nutrients and subsets of nutrients. For example fats were broken down in to saturated fatty acids, cholesterol, omega-3s and DHA .

They found that children who had higher fibre diets had significantly improved accuracy scores on the Flanker test. The results showed that soluble fibre was associated with overall accuracy and pectin was particularly linked to accuracy in the version of the test that required greater effort. The researchers postulate that the effects might be linked to better control of blood sugar and/or the interaction of the gut microbiota. Fibre cannot be assimilated into the body but is highly fermentable by the bacteria in the gut. Some of the important end products of this fermentation are short-chain fatty acids, which have been linked to reduced inflammation in the brain and increased BDNF, compound associated with the creation of new brain cells.

Whilst this study was conducted on children it is highly likely that the outcomes will be similar in adults.

• High soluble fibre foods: Oats and oat bran, beans, lentils, apples, pears.
• High insoluble fibre foods: Wheat bran and wholegrains, brown rice, seeds, fruit and vegetable skins.
• High pectin foods: Apples, pears, quince, peaches, plums, oranges, lemons, grapefruit, gooseberries, apricots, guava, carrots, tomatoes.

Reference

Khan, N. A., Raine, L. B., Drollette, E. S., Scudder, M. R., Kramer, A. F., & Hillman, C. H. (2015). Dietary Fiber Is Positively Associated with Cognitive Control among Prepubertal Children. The Journal of Nutrition, 145(1), 143–149. http://doi.org/10.3945/jn.114.198457

Gut Microbes Regulate Nerve Cell Myelination (Animal Model)

The prefrontal cortex (PFC), the foremost part of the brain, is the seat of what is called ‘executive function’. Executive functions are the higher order tasks of the brain (beyond regulating the systems and processes of the body) such as attention, planning, decision-making, memory, managing social interactions, making moral judgements and anticipating the consequences of a particular behaviour. The PFC also plays an important role in emotional functioning; regulating fear, anxiety, normal guilt, and PFC dysfunction is implicated in the development of mental disorders such as schizophrenia and autism spectrum disorders.

New research from University College Cork has uncovered an important role of the gut microbiome on the structure and functions of neurones in the PFC. In this study the researchers compared the brains of mice raised in ‘germ free’ conditions (i.e. no gut microbiome) with mice raised conventionally and those who spent the first part of their lives germ-free then were later introduced to the conventionally-raised animals, which would lead to some colonisation of the gut microbiome.

They found that over 221 genes behaved differently in the brains of the germ-free and ex-germ-free mice compared to those raised conventionally. The germ-free vs the conventional mice made up the biggest difference accounting for 190 of the 221 differently expressed genes. Many of these genes were involved in the task of myelination and these changes were confined to the PFC region of the brain. Myelin is the fatty sheath that surrounds a nerve cell, like the protective plastic coating around an electrical wire. Myelin aids the conductivity of the nerve cell, helping it to send messages faster and more efficiently. Failure in myelination is the cause for the loss of muscle function and control in Multiple Sclerosis, for example. This study was looking at the underlying biological mechanism so the researchers did not make any comment on the potential implications of these changes other than to note previous research showing increased anxiety in germ-free mice and stating ‘Our results further highlight the microbiota as a viable therapeutic target in psychiatric disorders’. They also note that the unusual changes in the myelin of the germ-free mice was corrected in the ex-germ-free mice, indicating that later colonisation of the gut microbiome normalised myelin gene expression in this important region of the brain.

Reference

Hoban, A. E., Stilling, R. M., Ryan, F. J., Shanahan, F., Dinan, T. G., Claesson, M. J., Clarke, G. & Cryan, J. F. (2016). Regulation of prefrontal cortex myelination by the microbiota. Translational Psychiatry, 6, e774. doi:10.1038/tp.2016.4

http://www.nature.com/tp/journal/v6/n4/full/tp201642a.html