Dr Dingle's Blog / probiotics
Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota has been shown to influence obesity and pain sensitivity.
Physiological pain plays a life-essential protective role, while acute or chronic pathological pain indicates a medical problem that needs treatment and imposes a medical challenge. Neurotransmitters, immune cells, and hormones have been demonstrated to contribute in pathogenesis of chronic pain.
Pain threshold is influenced by several factors, including obesity, which alters adipose tissue metabolic and endocrine functions leading to alterations in systemic physiology including an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. Studies have demonstrated that obese humans and rats are more sensitive to pain stimuli than normal weighted ones.
Previous studies have demonstrated a relationship between intestinal microbiota and diseases including pain disorders with probiotics having a positive effect.
In this study the mice taking probiotics had a significantly lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics.
Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870) on Mechanical Sensitivity in Diet-Induced Obesity Model
The integrity of our gut and our gut health is so important to our health but has largely been ignored until recently. The mucous membrane absorbs and assimilates foods and serves as a barrier to pathogens and other toxic substances. When this integrity is compromised the permeability of the gut may be altered, gut function erodes and we end up with many health conditions associated with inflammation and leaky gut.
The gut lining is composed of close fitting, thin cells separated by tight junctures, like a thin protein mortar. When the barrier is disrupted the intestines permeability increases allowing larger particles, bacteria, undigested foods or toxins to cross the barrier. This intestinal permeability, called leaky Gut, is linked with virtually all the gut related disorders including ulcerative colitis, Crohn’s disease, celiacs disease, and auto immune conditions including inflammatory joint disease, ankylosing spondylitis, juvenile onset arthritis, psoriatic arthritis, diabetes mellitus type one and primary biliary cirrhosis.
To maintain integrity and normal function of intestine, a delicate equilibrium must be reached between the microbiota and intestinal immune system. In a healthy body the immune system protects us against invasion and controls the commensal microorganisms. In return the beneficial bacteria provide essential nutrients to the gut cells and promote healthy immune responses in the gut.
A healthy microbiome contributes to the maintenance of intestinal epithelium barrier integrity maintaining the tight junctures, promoting intestinal cell repair, and even ensuring a healthy rate of cell turnover. It does this by maintenance of local cell nutrition and circulation and protection against pathogenic microorganisms.
Unlike most other cells in the body that get their energy and nutrients from the blood supply, more than 50% of the energy needs of the small intestine and more than 80% of the energy of the large intestines (where most of our microbiome is) comes directly from the food in the gut. This is not just a one off but with each turning over of gut cells which is over a period of just days, the barrier has to be continually re-established. The end result of this mutually beneficial co-habitation is a symbiotic relationship between the two partners, us and our microbiome. Any change in the relative proportions of the different bacteria alters the subsequent nutrients available and maintenance and protection for the digestive tract. If the right food and conditions are not there for a healthy microbiome then the nutrients are not available for the gut wall and the cells are damaged leading to damage to the integrity of the gut wall and leaky gut. This highlights the importance of eating the right foods for the microbiome to do their job and to maintain optimal gut health.
 Magalhaes et al., 2007.
Another reason to add some of the cabbage family to your daily diet, preferably raw is because of their gut healing properties and how they promote gut health through the gut microbiome. The Brassica family including cabbage, broccoli, brussel sprouts, kale, arugula (rocket), bok choy, cauliflower, collard greens, radish, turnip and others have been recognized for their gut healing and gut health properties for hundreds of years and modern epidemiologic studies have shown a frequent consumption of cruciferous vegetables is associated with lower risk of cancer, especially cancers of the digestive tract, bladder, breast, prostate, and lung. However, only now are we recognizing that many of these benefits are mediated through the microbiome and that their frequent consumption alters the composition of the microbiome.
Cruciferous vegetables are a rich source of glucosinolates a precursor to the Isothiocyanates (ITC), which exhibit powerful biological functions in fighting cancers, cardiovascular, neurodegenerative diseases and gut healing. The Isothiocyanates are a by product of specific plant enzymes (myrosinase) active during chewing or crushing when broccoli is consumed raw or lightly steamed, however, like all enzymes myrosinase is deactivated by cooking and ingestion of cooked broccoli typically provides only about one tenth the amount of isothiocyanates as that from raw broccoli. So to maximize the gut healing, gut health and overall benefits of these foods they are best eaten raw or just lightly steamed.
Instead when cooked cruciferous vegetables are consumed, gut bacteria are mainly responsible for ITC production in the gut. This is highlighted after taking oral antibiotics, the ITC’s availability and uptake decreases after eating cooked cruciferous vegetable. It also appears that there is considerable difference in the ability of individuals, due to individual differences in gut microbial community, to produce the isothiocyanates. Although, the gut community’s ability is altered over just 4 days. In one study feeding raw or cooked broccoli for four days or longer both changed the microbiota composition and caused a greater production of isothiocyanates. Interestingly, a three-day withdrawal from broccoli reversed the increased microbial metabolites suggesting that the microbiota requires four or more days of broccoli consumption and is reversible.
The lactic acid bacteria appear to have myrosinase-like activity and the fermented Brassica food products, such as sauerkraut and kimchi, are particularly rich in Lactobacillus, and a diet rich in Brassica may promote Lactobacillus growth in the colon.
The reason I call it the blood pressure smoothie is all of the ingredients have been multiple shown in scientific studies to reduce blood pressure. By no way is this meant to replace advice from you GP but you can share it with them and see if they are interested in preventing the problem rather than just treating it with pharmaceuticals. Remember also that I am not a GP I am just the guy who does all the research which is why I have a PhD.
4 ingredients in order of importance
Almonds (soaked for at least 8 hours)
Filtered re-mineralised ionized water.
(equal amounts of each ingredient excerpt a more water)
Extras for taste and minerals
Start by grinding the linseed and the almond in the smoothie maker.
Add the beetroot and the filtered water to make up to the constituency you need.
If you want to make it a bit sweeter add some ripe banana, dates or coconut water (and coconut meat if you have the whole coconut) as they are rich in Potassium (and other minerals) which is essential for muscle relaxation and tastes great. But wait till the banana is ripe for the best taste. You can also cold green tea instead of water to add to the antioxidant mix.
The properties that make this smoothie such a potent blood pressure mix is all of the ingredients have excellent antioxidant properties, rich in minerals and other nutrients liked with lowering blood pressure in scientific studies.
High blood pressure or hypertension is having a blood pressure reading of above of around 90mm Hg on 140mm Hg. Hypertension itself is not a disease but a condition or as an indicator of ‘increased risk’ of cardiovascular disease. Patients who are hypertensive have an increased risk of heart attack and stroke due to the direct correlation between the two. Hypertension also contributes significantly to the increased risk of kidney failure and other chronic illness.
In healthy people the cells of blood vessels produce the substance called nitric oxide (NO) which instructs smooth muscles surrounding arteries to relax. If they cant relax they stay rigid and you end up with high blood pressure. The NO is produced in a single layer of cells that line the inside of the arteries called the endothelium. If this tissue is damaged in the case of too much pressure, oxidation or through other means it stops producing NO and blood pressure rises.
Many of the beneficial actions of nutrition on lowering blood pressure results both directly and indirectly through improving endothelial tissue and NO production and release from this tissue. Two major pathways to increase NO are increase the rates of nitrates in the diet, the building block for NO, and L-Arginine which stimulate the enzyme to manufacture NO. Endothelial-derived NO also inhibits platelet adhesion, activation, secretion, and aggregation and promotes platelet disaggregation so you are less likely to have a stroke. A third mechanism that is absolutely critical is to protect and repair the endothelium, remember it is only one cell thick and very susceptible to damage. Vitamin C and antioxidants are essential for this part.
Diets high in dietary nitrate such as beetroot are associated with reduced blood pressure increased exercise performance as a result of vasodilation (expansion) of the blood vessels and a decreased incidence in cardiovascular disease. 100-200mg of beetroot per day has been shown to produce immediate effects of lowering blood pressure by around 15 mm of Hg. Beetroot is also rich in vitamins, phytochemicals and contains large amounts of iron and folic acid Mg, Na and Ca. Apart from the nitrates the major bioactive molecules in beet are polyphenols, flavonoids, betalains, therapeutic enzymes, ascorbic acid, and dehydroascorbic acid (DHAA). So they not only provide the ingredients for NO production but also help in repair and protection of the endothelium.
Almonds have one of the highest sources of L-Arginine (most nuts have lots of L-Arginine so you can substitute the almonds if you want) which stimulates NO synthesis. Studies of almonds have shown reductions of 5-6 mm of blood pressure. It is important to soak the almonds as they (all nuts and seeds) have enzyme-inhibiting factors in them which stop them from germinating until they have enough water. These enzyme inhibitors also stop the absorption of some nutrients, particularly minerals. When you soak the nuts many of the nutrients also become more available for digestion.
Flaxseed is rich in Omega 3 fatty acids, L Arginine (about 20% less than almonds), lignans, antioxidants and fiber that together probably provide benefits to patients with cardiovascular disease. Studies on consuming 30g of flaxseed have been shown to reduce blood pressure by up to 15 mm Hg.
A study of 20 volunteers, eight males and twelve females, who were given Bifidobacterium and Lactobacillus strains, either 30 min before breakfast (pre-prandial administration), or 30 min after breakfast (post-prandial administration) found no difference in the levels measured in the stools. Different theories have suggested the higher acidity in the empty stomach or the mixing in with the food might influence the amount of viable bacteria that populate the colon. While only a small number the study suggest take them any time.
The study also found probiotic supplement levels up to 1 month after the end of probiotic oral intake in both groups. It also reported a significant decrease in Firmicutes abundance which has been associated with weight gain and diabetes. The abundance of a particular stain Akkermansia muciniphila was increased compared to samples collected at the beginning of the experiment. This is important as it is the bacteria that increases with the diabetic drug metformin and is associated with breaking down the mucus build-up in the gut and stimulating energy production in the cells (the mitochondria). Yes that is how the drug metformin works. If they inject it directly into the blood it has no benefit at all. Yes the worlds most effective drug is just a prebiotic.
In this study the probiotic supplement showed the ability to modulate the gut microbiota composition, leading to a significant reduction of potentially harmful bacteria and an increase of beneficial ones. The two bacterial strains seemed able to exert a beneficial effect on the bacterial ecology of the gastrointestinal tract, as many significant positive changes in gut microbiota composition have been highlighted.
In the last years, their numerous beneficial properties and positive impact on human health have deeply been described. Nowadays, hundreds of different bacterial strains are available in the global probiotic market and consequently, the choice of the most suitable probiotic product becomes very difficult and fragmented. Lactobacilli and Bifidobacteria are the main microorganisms used as probiotics; indeed, numerous species belonging to these genera have been reported as safe and effective in improving the host’s health. Several studies showed that the combination of specific bacterial strains belonging to Lactobacillus and Bifidobacterium species can act in optimal synergy for restoring the intestinal balance.
Not only are probiotics considered beneficial to digestive health, and immune health but increasing evidence suggests direct and indirect interactions between gut microbiota (GM) and the central nervous system (CNS).
A large body of research has supported the presence of a pathway of communication between the gut and the brain, modulated by the gut microbiota, giving rise to the term “microbiota-gut-brain” axis. It is now thought that, through this pathway, microbiota can affect behaviour and modulate brain plasticity and cognitive function. In particular, studies have illustrated an association between the gut microbiota composition and cognitive processes such as learning and memory. Research has shown that the intestinal microbiota additionally contribute to the early development of normal social and cognitive behaviours 1. While probiotic and prebiotic supplementation can have a positive effect on mood and psychological symptoms such as depression and anxiety, stress as well as mental health issues including depression, Alzheimers and Parkinson’s diseases. This new area of research, called “psychobiotics” is where the beneficial bacteria (probiotics) or prebiotics that influence bacteria–brain relationships can exert positive emotional, cognitive, systemic, and neural benefits 2. This process is thought to occur primarily through the central nervous system (CNS) as well as through metabolic, hormonal and immune pathways.
Recent evidence indicates a clear association between changes in the microbiota and cognitive behaviors and there is increasing evidence on the effects of supplementing with probiotics on improving cognitive disorders 3. One of the earliest studies found that the wrong type of bacteria added to the gut of germ free animals (containing no microbiota), can cause stress related negative behavious while administration of probiotics can improve cognitive behaviors including learning and memory 1.
In a clinical trial conducted among 60 Alzheimer's patients where the probiotic supplemented group took 200 ml/day probiotic milk for 12 weeks, the probiotic group showed a significant improvement in the MMSE (Mini-mental state examination) which is a measure of cognitive function. In addition, they reported lower levels of oxidation and inflammation, blood fats (tryglicerides) and improved insulin resistance and Beta cell (pancreas) function which controls and stores insulin in the probiotic group compared to the control group 4. A pretty good reason to supplement with probiotics.
Growing research also shows probiotic supplements may be used therapeutically to modify stress responses and symptoms of anxiety and depression 5,6,7,8. One study found that a short 3-week intervention with probiotics-containing milk drink improved mood scores compared to participants who received a placebo. Although, improvement in mood was only observed for participants who showed elevated symptoms of depression at the beginning 9. A second study found that a month of probiotic supplementation significantly improved depression and anger 10. In a triple-blind study of 20 healthy participants without a current mood disorder over 4 weeks, probiotics significantly reduced negative thoughts associated with a sad mood compared to placebo. The positive effect was mostly because of reduced rumination and aggressive thoughts 11. While a study of people with chronic fatigue syndrome found that supplementing with probiotics for 2 months significantly reduced their anxiety scores 12.
Similar results have also been shown in animal studies. In a study of healthy mice researchers observed a reduction in anxious and depressive behavior after feeding healthy mice with probiotics 13. A similar result was shown in adult rats with a reduction in depressive-like behaviors after feeding them with Bifidobacterium species. The effect was comparable to the effects of administering the antidepressant citalopram 14.
Stress and anxiety disorders are two of the most common psychiatric illnesses worldwide, affecting both children and adults. Increasing numbers of studies have suggested that the gut microbiota is involved in the pathophysiology of stress-related disorders. For example, a number of studies have now shown that certain strains of bacteria increase anxious behaviour while others reduce it. One study found that participants who were given a mixture of probiotics containing Lactobacillus and Bifidobacterium species showed significantly less psychological distress than matched controls 15. A recent (November 2016) meta-analysis of seven studies with around 300 participants showed that supplementation with probiotics resulted in a significant improvement in psychological symptoms of depression, anxiety, and perceived stress in healthy human volunteers 16.
However, probiotics and the effects on our moods appears to be a two way street. While the gut microbiome can alter moods, our moods can also alter our gut microbiome. Chronic stress can cause behavioral, cognitive, biochemical, and gut microbiota aberrations. In a study of 1002 cases and controls followed up for 12 years, those with gut disorders had elevated levels of anxiety and depression at baseline, but also those with higher levels of anxiety and depression were more likely to have gut disorders at follow-up 17.
Animal studies have also shown certain strains of Lactobacillus exert a positive effect on anxiety-related behavior and responses to stress 13,18. In a study on rats subjected to 21 days of stress the results showed that administration of probiotics improved the stress-induced behavioral (anxiety and depression) and cognitive dysfunction, showing an effect similar to and better than that of an antidepressant. It also resulted in lower stress hormones and improved blood parameters suggesting it was dealing with some of the underlying mechanisms 18.
Other studies have noted that microbiota have an important influence on the development of cognitive processes in young mice 1. Depletion of a normal gut microbiome in early life, especially during the post-weaning period, may affect cognitive and social behaviours in the brain through the alteration of neuropeptides (chemical messengers) such as vasopressin and oxytocin 19,20. In fact, the research suggests a strong role of the gut microbiota in autism spectrum disorder. Interestingly, treatment of mice with autism with probiotics has shown to ameliorate autism related traits 21. In another twist on this, a study of 75 pregnant women given probiotics 4 weeks before their due dates and then continued giving the probiotics to the infants, or to the mothers if they were breastfeeding for 6 months did not develop any ADHD or Asperger’s after being followed for 13 years. 17.1% of the children in the placebo group developed ADHD or Asperger’s. Not one child in the probiotic group did 22.
Importantly, studies have shown that multispecies probiotics (i.e., combining different strains of specific genera) can have increased effectiveness through an additive effect of specific strain properties such as colonization of different niches, enhanced adhesion and induction of an optimal pH range, as compared to mono-species supplements 23,24. So take a mixed species supplement for the best results.
- Gareau et al 2014
- Liang et al 2015
- Bhattacharjee and Lukiv, 2013
- Elmira Akbari1 et al 2016
- Logan and katzman 2005,
- Cryan and O’Mahony, 2011,
- Bruce-Keller et al 2015,
- Savignac et al 2015
- Benton et al 2006)
- Gut Microbes 2011
- Steenbergen L., et al. 2015
- Gut Pathology 2009;1:6-10
- Bravo et al 2011
- Desbonnet et al 2010
- Messaoudi et al 2011
- McKean et al. 2016
- Koloski et al, 2016
- Luo, J. et al. 2014
- Desbonnet L., et al. 2015,
- Sampson and Mazmanian. 2015
- Hsiao et al. Cell. 2013
- Pediatr Res 2015;77:823-8
- Timmerman et al 2004
- Chapman et al 2011