Dr Dingle's Blog / gut
A short time between eating your last meal and sleep can increase your risk of breast and prostate cancer.
One of the most important factors in regulating our gut health, digestion and controlling our microbiome is the pH or acid level.
While often mentioned in terms of the stomach, the pH has a controlling role to play in the health of the entire GI tract from the mouth to the anus; changes in the “normal” pH anywhere in the gut can have major implications on the rest of the GI tract. The pH scale goes from 1, being very acidic, to 14, being very alkaline. The level in our blood and tissues should be constantly around 7.36, neutral, and the level in our GI tract varies from 1 to 8. We cover this a lot more in our book Overcoming Illness, which focuses on the role of inflammation, oxidation and acidosis in illness.
After initial breakdown by chewing, food is churned by the smooth muscles of the stomach and is broken down by hydrochloric acid and stomach juices (enzymes). The pH of the stomach is highly acidic, around 1.5 (1.0 to 2.5) due to the hydrochloric acid that helps to kill harmful micro-organisms, denature protein for digestion, and help create favourable conditions for the enzymes in the stomach juices, such as pepsinogen. Not to mention sending messages along the GI tract that everything is working well in the stomach. If the pH is too high, say 3 or 4 (low acidity and more alkaline), then the system does not work and you end up with poor gut health, digestive and health complications. For example, premature infants have less acidic stomachs (pH more than 4) and as a result are susceptible to increased gut infections. Similarly, the elderly show relatively low stomach acidity and a large number of people, more than 30%, over the age of 60 have very little or no hydrochloric acid in their stomachs.
Similarly, in gastric bypass weight loss surgery, roughly 60% of the stomach is removed. A consequence of this procedure is an increase in gastric pH levels that range from 5.7 to 6.8 (not 1.5) making it more alkaline and, as a result, more likely to experience microbial overgrowth. We see similar patterns in other clinical cases such as acid reflux in which treatment involves the use of proton-pump inhibitors and celiac disease where delayed gastric emptying is associated with reduced acidity and increased disease.
Unfortunately, acid reflux is often wrongly treated as a condition that involves the production of too much acid. It is, in fact, the stomach finding it difficult to digest the foods, most commonly as a result of not having enough acid to complete digestion. Medications (see my other posts) which further reduce stomach acid have serious and sometimes deadly side effects on health, the digestive process and the gut microbiota. Acid reflux affects about 20% of the adult population and is much higher in older people, which is consistent with studies showing lower stomach acid as we age.
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While antibiotics have been lifesaving, the over-prescription of antibiotics has sparked the evolution of drug-resistant strains of life threatening bacteria, resulting in tens of thousands of deaths each year. The US Centers for Disease Control estimate that up to 50% of antibiotics prescribed in the US are unnecessary. Unfortunately, the use of antibiotics is often prescribed for those groups who are more vulnerable to dysbiosis, including infants born via C-section and in those born preterm, compared to term infants born vaginally, potentially compounding the problems. Micro-organisms such as bacteria, fungi, viruses, and parasites cause many of the world’s diseases, yet only bacterial infections are usually susceptible to treatment with commonly prescribed antibiotics.
However, more subtle side effects of antibiotics on the gut microbiome are only just beginning to be discovered. Broad-spectrum antibiotics can impact up to 30% of the bacteria among the human microbiota, resulting in severe loss of species and function and begins immediately following antibiotic administration. The effects can sometimes last for years after its cessation, and may also lead to the total extinction of some beneficial microbial species. As few as three days of treatment with the most commonly prescribed antibiotics can result in sustained reductions in microbiota diversity. A typical two-week course of high-dose antibiotic treatment, as might be used for an ear infection, can wipe out most of the beneficial gut microbes.
These antibiotic-induced changes in the microbiota have been linked to many disease states including increased infections, metabolic disturbances, obesity, autoimmunity, and mental health conditions. Common outcomes of antibiotics the antibiotic-disturbed gut microbiota are diarrhea and infections with Clostridium difficile, particularly in infants.
Early life exposure to antibiotics presents the greatest risk of long-term damage to the gut microbiota and the more you take, the worse it is. In young children, antibiotics may change the development of the “adult” microbiota, and not allow its normal maturation. It has also been hypothesized to cause a delay in microbial maturation from six to 12 months after birth. Early life exposure is also associated with numerous diseases later in life including IBD, obesity, and asthma, as well as the development of immune-mediated metabolic and neurological diseases.
In a meta-analysis of eight studies including 12,082 subjects, antibiotic use in the first year of life was significantly associated with two-fold (200%) increased chance of the child having asthma. One study reported the use of antibiotics in newborns increased the risk of developing asthma by 24 times. Probiotics during the neonatal period were protective and reduced the risk by as much as 86% for childhood asthma for kids at risk. Studies of mice treated with antibiotics in early life revealed altered microbial populations within the gut microbiota and consequently increased the susceptibility of these mice to asthma.
Antibiotic use has also been shown to have long-term effects on brain neurochemistry and behavior. Such use is known to alter the intestinal microbiome with subsequent changes in microbiota to gut-brain axis and result in poorer neuro-cognitive outcomes later in life.
Even treatment with a single antibiotic course was associated with a 25% higher risk for depression and the risk increased with recurrent antibiotic exposures to 40% for two to five courses and 56% for more than five courses of antibiotics. The higher the rates of antibiotic use, the higher the rates of depression. Animal studies have shown that high doses of a cocktail of antibiotics induced lasting changes in gut microbiota associated with behavioural alterations.
Animal studies of early life exposure to antibiotics show lasting immune and metabolic consequences. Administration of low doses of penicillin to mice early in life increases the risk of weight gain and obesity and promotes lipid accumulation by altering the gut microbiota. Mice treated continuously with low-dose penicillin from one week before birth until weaning exhibited higher body weight and fat mass in adulthood, although the microbial structure returned to normal after four weeks of antibiotics cessation. There is also evidence of antibiotics playing a role in the development of IBD in children and that antibiotic usage during the first year of life was more common in those diagnosed with IBD later in life.
In human studies, mother’s use of antibiotics during pregnancy is consistently associated with cow’s milk allergy, wheeze, asthma, and atopic dermatitis, with the strongest association for antibiotic use in the third trimester of pregnancy. A study of 306 children with asthma showed that mother’s use of antibiotics during pregnancy increased the risk by a whopping four times (390%). Low-dose penicillin in late pregnancy and early postnatal life in the offspring of mice resulted in lasting effects on gut microbiota, increased brain inflammation, and resulted in anxiety-like behaviours and displays of aggression. Similar results have been shown for antibiotic exposure through breastfeeding.
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The human stomach, when healthy, is not a suitable host for micro-organisms, but in pathological conditions such as gastritis, when gastric acid secretion is impaired, microbial overgrowth can be observed. The use of gastric acid suppression drugs has been shown to have profound effects on the microbiome. Acid-blocking drugs, or proton pump inhibitors (PPIs) used for gastroesophageal reflux disease (GERD) to reduce gastric acid secretion, are among the most commonly prescribed medications in the world with approximately 6%–15% of the general population receiving acid suppression therapy. Once initiated, they are often used for long periods of time without question, despite the guidelines saying “for short term use only.”
PPIs increase the stomach pH to make it less acidic, which is what they are designed to do, and as a result, change the composition of the intestinal microbiota and impact the pH of the rest of the gut. They are associated with a decrease in small bowel beneficial Bifidobacteria and increase in the toxic gram-negative bacteria, as well as being associated with a significant decline in microbial diversity within seven days of beginning therapy.
PPIs dramatically increase the risk of stomach bacterial overgrowth (SBO) and small intestinal bacterial overgrowth (SIBO), with increased risk of these bacteria getting into the blood and the potentially fatal infection, Clostridium difficile. Bifidobacteriaceae, important and beneficial bacteria of human gastrointestinal microbiota, can over-colonise the stomach of people with low stomach acid. Bifidobacteriaceae species, typically found in the oral cavity, readily colonise the low acid stomach and become good bacteria but in the wrong place as a result of altered pH.
Proton pump inhibitors also promote progression of both alcoholic and non-alcoholic fatty liver disease in mice and contribute to the increasing incidence of chronic liver disease as a result of dysbiosis. The list of side effects for PPIs is extensive, serious and even life-threatening and they are all mediated through the gut.
A growing number of studies are showing connections between autoimmune conditions linked with dysbiosis, including antibiotics and the use of protein pump inhibitors (PPIs) in controlling gastric reflux. The use of PPIs can potentially create far greater problems in the long run.
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Another study shows that the stress around you increases your risk of putting on weight, increases your risk of diabetes2 and reducing the stress helps with weight loss. The stress this time was living in a poorer environment. But many studies have shown multiple forms of stress works the same way.
Persistently elevated cortisol levels have been closely tied to weight gain, increased abdominal fat, and other aspects of metabolic syndrome, a collection of things that includes obesity and pre-diabetes.
When cortisol is released in response to stress, it signals the body to shift energy production into overdrive. It’s a signal for organs and various tissues in the body to accelerate production of glucose, the sugar that fuels our muscles, by breaking down carbohydrates and protein. As part of its role in freeing up energy, chronic exposure to cortisol also increases cravings for high-sugar, high-fat foods, and increases the body’s resistance to insulin, the hormone that signals the body’s cells to absorb sugar.
In support of this in mice, stress increases cravings for energy-dense foods; in people, comfort- or stress-eating is a familiar phenomenon.
in addition consistent exposure to cortisol may re-wire the brain, for example, shrinking the pre-frontal cortex and bulking up the amygdala. Over time cortisol can increase the risk for depression and mental illness.
The most important aspect of dysbiosis is that a loss of total microbial diversity which represents the first link in the chain of events leading to the development of local and body wide inflammation. Multiple human conditions have been associated with dysbiosis, including autoimmune and auto inflammatory disorders, such as allergies, cardio vascular, metabolic disorders (diabetes, obesity and non-alcoholic fatty liver disease), various cancers and inflammatory bowel disease such as Crohn's and ulcerative colitis (UC), celiac disease, and neurological disorders including autism.
Once inflammation starts it appears that these opportunistic microorganisms are able to exploit the inflamed environment and expand their numbers to become an even bigger problem.
There appear to be three types of dysbiosis that more often than not, occur together to create the problem. These include (i) loss of beneficial microbial organisms perhaps through the use of antibiotics, (ii) expansion of pathobionts or potentially harmful microorganisms as a result of too much processed foods and (iii) loss of overall microbial diversity. It is likely that dysbiosis encompasses all three of these manifestations at the same time to influence disease.
The challenge is that the Dysbiotic microbial ecosystem can become resilient over time and may become hard to alter. In one study while dieting rapidly reversed the metabolic problems associated with a high fat diet, the dysbiosis in mice after a 4-week high fat diet persisted up to 21 weeks after returning to normal chow diet. It did however change after 21 weeks.
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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.
Your gut microbiome has an astonishing ability to keep you healthy or ill. The list of diseases that we know of that are linked to the intestinal microbiota grows every day and these diseases are usually complex in terms of both how the disease develops and complications. Having the right balance of good microorganisms in our gut and good gut health is not only essential for good digestion but also in the prevention of or reversing chronic diseases, including.
Poor gut health has been linked with a long list of illnesses including
Asthma and Allergies
Cancers (especially digestive cancers, i.e. bowel and colon and brain tumours)
Inflammatory Bowel Disease including SIBO, Crohn’s and Ulcerative colitis
Cardio vascular disease
High blood pressure
Depression, Anxiety and Stress
Skin health and ageing
Eczema, Dermatitis and Psoriasis
Immune system function including susceptibility and tolerance to viruses and bacterial infections like cold and flu.
Colic, Constipation and Diarrhea
Celiac disease and Gluten and lactose intolerance
The list goes on. For example, even in the area of mental illness we have conditions such as
Depression, Anxiety and Stress
ADHD & Autism
Focus and memory
Learning, mental productivity and cognitive decline. As well as controlling some of our needs and desires i.e. food cravings and appetite, our relationships and our social interactions.
These are all impacted by gut health. Because of the role of inflammation, oxidation nutrition and the many functions of the gut microbiome there is not a health condition that is not influenced by the gut microbiome either directly or indirectly.
Because of the multiple functions of the microbiota dysbiosis can manifest as many and multiple health conditions often termed comormidity or multi morbidity. It is not one disease it manifests as many. For example, large studies have shown the multi-morbidity of eczema, rhinitis, and asthma. Inflammatory Bowel Disease (IBD) patients will also frequently suffer from rheumatologic manifestations, liver multimorbidities and lung, namely chronic obstructive pulmonary disease and bronchial asthma, bronchitis and other chronic respiratory disorders in the adult population, gallbladder disease, heart disease and associated morbidity and mortality, anxiety, stress and depression, as well as arthritis, psoriasis, and pericarditis. In one study of 47325 patients they reported 20 different immune mediate diseases associated with IBD including some of those mentioned above and celiac disease, type 1 diabetes, rheumatoid arthritis, and ankylosing spondylitis.
This evidence strongly shows any health condition will have many layers of disease occurring throughout the body at any one time that are related but not connected at the time of diagnosis.
Arguable the biggest health problem facing us today is gut health rivaling the current obesity crisis and tobacco smoking in its impact on our health. Every health condition is linked to gut health and gut healing either directly or indirectly through inflammation and oxidation. Historically every culture understood this and were involved in extensive practices of gut healing and even our own up until 60 or so years ago. The first thing health practitioners throughout history would do is to start to fix the gut.
Until recently the positive effects of the gut microbiome on our digestive system and health has been severely under rated. Wisdom of Chinese doctors from centuries ago, who somehow knew that the intestines were not merely a digestive organ, but the centre of health and wellbeing. Hippocrates was recorded as saying that all illness begins in the gut. Throughout history from the Egyptians till around 80 years ago medicine and the bowels were frequently mentioned in the same sentence and good health revolved around gut health.
Even today the nomadic Maasai tribes in Africa attribute most illnesses to the effect of “pollutants” that block or inhibit digestion. In these communities the plants are used to cure diseases served mainly as strong purgatives and emetics; they "cleanse" the body and digestive system from polluting substances.
With thousands of studies released each year the gut is known to play a major role in many health conditions including mental health issues, cardiovascular disease, allergies and asthma, autoimmune diseases, some cancers and even diabetes and weight gain. Many of these conditions which are now reaching epidemic proportions have been linked to a dysfunctional gut. Studies have shown a strong link between mental health issues including depression and what is called the gut brain axis. We also know the gut is the centre of our immune system and is strongly influenced by the gut microbiome. As a result the gut has a strong link with allergies and asthma. Peanut allergies for example are not caused by peanuts they are brought about by a dysfunctional gut microbiome.
Antibiotics and many gut medications used for controlling acid reflux have been shown to be devastating to gut health a healthy gut microbiome, as well as many of the chemicals we use around the homes and even the personal care products we apply to our skin. Even our activities either promote gut health and gut healing or harm it. Stress sends messages to the opportunistic (bad) microorganisms in the gut to tell them to start to take over from the good ones. Exercise promotes gut health and healing while no exercise or too much exercise does the exact opposite.
Fortunately, in animal studies we know that many of these conditions can be improved and even reversed if the gut microbiome is repaired. 50% of Parkinson’s Disease has been directly linked with poor gut health while improving the gut microbiome has been shown to dramatically improve symptoms.
The research also shows that while probiotics can be useful in gut healing, repairing the gut microbiome requires an understanding of what encourages a healthy gut microbiome in our diet and lifestyle as well as what causes a dysfunctional microbiome. We now know that all the healthy foods we eat, the vegetables, nuts, seeds, herbs, spices and fruit all feed the gut microbiome which then feeds us and looks after our health. All the studies on healthy diets from the Mediterranean to the original Japanese or the low inflammatory diet (DII) benefit us because they work through the gut to promote gut health and subsequently our health.