The gut is a mystery to most. Food goes in, stuff happens, and poo comes out. We all know we need to eat and drink to feed this ‘process’ and as a result, we live. Science has revealed how the digestive system works and knows what all the different parts do.
In this podcast (Episode 145 – Gut – Acid Vs Alkaline Debate), we go through each organ and highlight what each part does, with special emphases on the pH (how acid) some parts are and how this affects digestion. For example, we know the stomach is a pit of acid (i.e. has a very low pH), yet the first part of the small intestine (the part that immediately follows the stomach) is highly alkali (in other words has a higher pH).
We also bust the whole ‘acid is bad’ myth showing that some acids actually protect against cancer. We talk about ‘acid forming diets’ and how they affect the gut.
What does your gut do – The physiology of the gut?
- Appetite and eating
- Digestion and absorption of nutrients
- Detoxification and elimination
- Microbiome home
- Digestion, creation and absorption of nutrients
- Creation of synergistic substances
- Performance and energy
- Muscle gain
- Fat loss
Acid and alkaline changes through the gut
Forget the general rules people say about how being alkaline is good and acid is bad blah blah blah. We are all smarter than that now. We won’t go into that in this blog. We have more important concepts to discuss.
PH is a scale from 0 to 14 used to measure of acidity or alkalinity. Low numbers are acid and high numbers are alkaline and around 7 in the middle is neutral (pure water has a pH of 7).
The pH in the human digestive tract varies as it moves through the various compartments of this internal tube that is capable of breaking down foods and drinks into their components for us to take in the good stuff we need and eliminate the waste.
The pH of saliva is neutral 6.5 – 7.5. It lubricates and allows us to chew and mechanically starts the pre-digestion and signals the rest of the gut to get ready to do some digesting. After we chew and swallow food it then enters the upper portion of the stomach which has an acidic pH 4.0 – 6.5. The food continues the “predigestion” phase while the lower portion of the stomach is secreting and accumulating hydrochloric acid (HCI) and pepsin to get to an extremely acidic pH 1.5 – 4.0. After the food mixes with these juices and makes a an acid slurry called chyme it then enters the duodenum (small intestine) where the it suddenly changes alkaline to pH 7.0 – 8.5.
This is where 90% of the absorption of nutrients is taken in by the body while the waste products are passed out through the colon. The pH of the colon can vary dramatically between pH 4.0 – 7.0. The varying pH in the colon is due to many factors including; stomach not acid enough, duodenum not alkaline enough, varying production of acids by gut flora from changing fibre or changing bugs and certain supplementation with acid, antacids, enzymes, fibre etc. So, an acidic gut is beneficial for overall gut health. ‘Alkalising’ the gut is a really bad idea.
Detoxification and elimination – The bugs!
There are 10 times as many gut bugs as there are cells in the human body, so it is hardly surprising they have an amazing effect on human detoxification, digestion and elimination. This huge effect is based on having the right bugs in your gut. After all, if the wrong kind of bugs take over, you can have problems with pretty much any system in your body.
The old way to fix the bugs in your gut was to take potent herbs or medicines that simply wiped out the gut bugs. You then replaced the bugs with a few different kind or beneficial bugs (commonly known as probiotics) and then ate well. This is how naturopaths operated for many years.
The good news is that now we are using natural polyphenols already supposed to be in your diet (but are sadly lacking due to todays processing and growth of foods) to rebalance the gut bugs. These are termed ‘Modbiotics’ and they enter the gut, kill the bad bugs and stimulate the growth of good bugs. This breakthrough means that we can more effectively treat people with ‘bad bug’ overgrowth (such as Candida), without doing harm to the good guys in the gut.
How is the gut is involved?
The bugs usually hang out in the large intestine and small intestine where they break down soluble fibres into short chain fatty acids. These fatty acids feed the colon and provide a nice acidic environment for the gut, where absorption can take place of your nutrients. Contrary to popular belief, these acids also protect us against cancer (despite some still believing acid causes cancer).
The first line of defence
The gut is the first line of defence to a host of potential toxins. After all, you swallow all sorts of stuff daily by the plate full! Think about it. Over your life, tonnes of stuff goes in your mouth and the body magically turns it into you. Even if you ingest a toxin, you will probably throw it up. If it gets passed this mechanism, your body has wonderful detoxification mechanisms which usually occur in the liver.
Your liver – CYP450 enzyme system
Your liver is a pretty cool organ. It has an amazing array functions, but this article will focus on the benefits liver offers for detoxification.
There are simply put, 2 phases of liver detoxification. Phase 1 makes the sticky, fat soluble toxins and makes them more water soluble. Phase 2 of liver detoxification sticks things like amino acids on these toxins, so they can be secreted from the body. This amazing process goes on day and night and without our knowledge. We can’t feel it, which is essentially a problem. If we could feel it, we may intuitively reduce the amount of bad food/toxic food that has adverse effects on our general health.
Gut wall integrity and exposure
Ok, assume we ignore our liver and eat bad food anyway. Strangely, we may not even call it bad food! Some foods that may be considered healthy include staple foods like wheat and dairy. These foods directly cause inflammation which compromise gut wall integrity. Also, we could be eating carbohydrate rich foods which stimulate the growth in bad bugs which, again damage the gut. Or, you could even be doing both at the same time (say you eat Weetbix and cow’s milk for breakfast). Unfortunately, some people eat this stuff and some even eat these toxic foods daily.
Nrf2 is a key regulator of expression of cytoprotective genes required for stress resistance. Nrf2 consists of seven Neh (Nrf2-EHC homology) domains, which regulate its activity by binding to other proteins or to DNA. The Neh1 domain is essential for Nrf2’s transcriptional activity, since it contains the bZIP DNA binding region and mediates interaction with sMAF (small masculoaponeurotic fibrosarcoma) proteins.
Upon sMAF binding, Nrf2 targets so-called AREs (antioxidant response elements) in the promoter region of several hundred genes, including many that code for cytoprotective proteins. These gene products include essential proteins of the glutathione (e.g., glutamate-cysteine ligase) and thioredoxin (e.g., thioredoxin reductase) system, which comprise the most important cellular redox buffers. In addition, Nrf2 regulates genes whose products are required for detoxification of ROS and xenobiotics (e.g., NQO1 (NAD(P)H dehydrogenase [quinone] 1)), NADPH regeneration (e.g., glucose-6-phosphate dehydrogenase), and heme and iron metabolism (e.g., HO-1 (heme oxygenase 1)). Since inflammation is associated with oxidative stress, the Nrf2 pathway is believed to play an important role in the pathogenesis of cancer and common inflammatory and neurodegenerative diseases.
In general, Nrf2 protects from infection, and an inverse correlation between infection and a decline in Nrf2 activity has been demonstrated. For example, viruses, such as hepatitis C virus or HIV, inhibit or decrease Nrf2. In contrast, Marburg virus and hepatitis B virus induce Nrf2 expression. Recently, it has been established that Nrf2 directly prevents transcription of genes encoding the pro-inflammatory cytokines IL-6, proIL-1β and proIL-1α, although the underlying molecular mechanisms are incompletely understood.
First pass metabolism
First-pass elimination takes place when a drug is metabolised between its site of administration and the site of sampling for measurement of drug concentration. Clinically, first-pass metabolism is important when the fraction of the dose administered that escapes metabolism is small and variable. The liver is usually assumed to be the major site of first-pass metabolism of a drug administered orally, but other potential sites are the gastrointestinal tract, blood, vascular endothelium, lungs, and the arm from which venous samples are taken. Bioavailability, defined as the ratio of the areas under the blood concentration-time curves, after extra- and intravascular drug administration (corrected for dosage if necessary), is often used as a measure of the extent of first-pass metabolism. When several sites of first-pass metabolism are in series, the bioavailability is the product of the fractions of drug entering the tissue that escape loss at each site. The extent of first-pass metabolism in the liver and intestinal wall depends on a number of physiological factors. The major factors are enzyme activity, plasma protein and blood cell binding, and gastrointestinal motility. Models that describe the dependence of bioavailability on changes in these physiological variables have been developed for drugs subject to first-pass metabolism only in the liver. Two that have been applied widely are the ‘well-stirred’ and ‘parallel tube’ models. Discrimination between the 2 models may be performed under linear conditions in which all pharmacokinetic parameters are independent of concentration and time. The predictions of the models are similar when bioavailability is large but differ dramatically when bioavailability is small. The ‘parallel tube’ model always predicts a much greater change in bioavailability than the ‘well-stirred’ model for a given change in drug-metabolising enzyme activity, blood flow, or fraction of drug unbound. Many clinically important drugs undergo considerable first-pass metabolism after an oral dose. Drugs in this category include alprenolol, amitriptyline, dihydroergotamine, 5-fluorouracil, hydralazine, isoprenaline (isoproterenol), lignocaine (lidocaine), lorcainide, pethidine (meperidine), mercaptopurine, metoprolol, morphine, neostigmine, nifedipine, pentazocine and propranolol. One major therapeutic implication of extensive first-pass metabolism is that much larger oral doses than intravenous doses are required to achieve equivalent plasma concentrations. For some drugs, extensive first-pass metabolism precludes their use as oral agents (e. g. lignocaine, naloxone and glyceryl trinitrate).
Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size), transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes. Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein (MRP) 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity. In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants (such as sporadic gall bladder emptying), have been developed. In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.
Bile is a complex fluid containing water, electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin that flows through the biliary tract into the small intestine. There are two fundamentally important functions of bile in all species:
Bile contains bile acids, which are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine.
Many waste products, including bilirubin, are eliminated from the body by secretion into bile and elimination in feces.
Adult humans produce 400 to 800 ml of bile daily, and other animals proportionately similar amounts. The secretion of bile can be considered to occur in two stages:
Initially, hepatocytes secrete bile into canaliculi, from which it flows into bile ducts. This hepatic bile contains large quantities of bile acids, cholesterol and other organic molecules.
As bile flows through the bile ducts it is modified by addition of a watery, bicarbonate-rich secretion from ductal epithelial cells.
In species with a gallbladder (man and most domestic animals except horses and rats), further modification of bile occurs in that organ. The gall bladder stores and concentrates bile during the fasting state. Typically, bile is concentrated five-fold in the gall bladder by absorption of water and small electrolytes – virtually all of the organic molecules are retained.
Secretion into bile is a major route for eliminating cholesterol. Free cholesterol is virtually insoluble in aqueous solutions, but in bile, it is made soluble by bile acids and lipids like lecithin. Gallstones, most of which are composed predominantly of cholesterol, result from processes that allow cholesterol to precipitate from solution in bile.
Role of Bile Acids in Fat Digestion and Absorption
Bile acids are derivatives of cholesterol synthesized in the hepatocyte. Cholesterol, ingested as part of the diet or derived from hepatic synthesis is converted into the bile acids cholic and chenodeoxycholic acids, which are then conjugated to an amino acid (glycine or taurine) to yield the conjugated form that is actively secreted into cannaliculi.
Bile acids are facial amphipathic, that is, they contain both hydrophobic (lipid soluble) and polar (hydrophilic) faces. The cholesterol-derived portion of a bile acid has one face that is hydrophobic (that with methyl groups) and one that is hydrophilic (that with the hydroxyl groups); the amino acid conjugate is polar and hydrophilic.
Their amphipathic nature enables bile acids to carry out two important functions:
Emulsification of lipid aggregates: Bile acids have detergent action on particles of dietary fat which causes fat globules to break down or be emulsified into minute, microscopic droplets. Emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplets.
Solubilization and transport of lipids in an aqueous environment: Bile acids are lipid carriers and are able to solubilize many lipids by forming micelles – aggregates of lipids such as fatty acids, cholesterol and monoglycerides – that remain suspended in water. Bile acids are also critical for transport and absorption of the fat-soluble vitamins.
Role of Bile Acids in Cholesterol Homeostasis
Hepatic synthesis of bile acids accounts for the majority of cholesterol breakdown in the body. In humans, roughly 500 mg of cholesterol are converted to bile acids and eliminated in bile every day. This route for elimination of excess cholesterol is probably important in all animals, but particularly in situations of massive cholesterol ingestion.
Interestingly, it has recently been demonstrated that bile acids participate in cholesterol metabolism by functioning as hormones that alter the transcription of the rate-limiting enzyme in cholesterol biosynthesis.
Bowel transit time
How long is a piece of string? That is how long your transit time is. Ok, usually it is 24 to 48 hours, but it can take days. In an ideal world, we should be aiming for 1-2 bowel motions per day. 1 is ok, as is 3. Obviously, your stool should be nicely formed, nice and brown and, well you get where I am going here. Anything weird or out of the ordinary really should be investigated.
Apart from getting diarrhoea, most people have transit times that are too slow due mainly to the overconsumption of refined foods and the under-consumption of fibre rich plant food. Especially, we need to focus on the soluble fibres found in fruits, vegies, nuts, seeds and salads. Also, we typically don’t exercise enough and may not drink enough water. Any of these factors can cause dramas and reduce our bowel transit times.
You may not understand the science of the gut and how the different bacteria and enzymes can influence our health, but beta-glucuronidase is a very important enzyme within the gut and is involved in phase 2 of liver detoxification. This is an enzyme that is plays a pivotal role in digestion, particularly in breaking down certain things such as complex carbohydrates, detoxification of estrogen, thyroid hormone and other environmental toxins.
If however the levels of beta-glucuronidase enzyme get too high, then this creates a very undesirable situation as you will start to reabsorb hormones like estrogen and toxins that should be eliminated.
This is one of the main causes behind high estrogen, many people take DIM supplements to improve estrogen detoxification but if your phase 2 of liver detoxification is not working well then you can reabsorb them back into your body, no matter how much DIM or broccoli you eat.
If your levels get too high of beta-glucuronidase then this can interrupt the body’s natural detoxification process. The liver can’t work to detoxify your body if levels of beta-glucuronidase are too high. When your body comes into contact with toxins or environmental chemicals, they are re-absorbed back into the body rather than being eliminated through the gut. These can make you sick over time and can lead to a whole host of health conditions in the future. So when the liver can’t properly work through the detoxification process, you are hurting your health now and in the long term as well.
Detoxification Pathways and bowel elimination
Detoxification and elimination is a very complex process. Our detoxification and elimination systems of our body is designed for general clean up and maintenance of our body but also is a very important part of our innate survival mechanism and must quickly respond to poisons, venoms and toxins.
This survival mechanism was designed to handle life-threatening stress. But we can’t afford to wait and see if a stress is life-threatening or not in case it kills you; so our body does not wait to see if it is a mold, infection, allergen, pollutant, pesticide, plastics, contraceptive or HRT or a poison or venom so it up-regulates the pathway necessary to clear; and because we are exposed to a lot this stuff (except poison and venom) all the time the pathways stay up and run faster than others.
The diet is a mixture of carcinogens, mutagens, and protective agents that are all metabolized by detoxification enzymes.
Any detoxification strategy must include;
- a) reducing toxic exposure and
- b) clean eating of a balanced diet to supply the modbiotics, antioxidants, amino acids, vitamins and other phytonutrients required for efficient detoxification and elimination of waste and toxins
Microbiome and detoxification
– polyphenols and Modbiotics – antioxidants, phase 1 and phase 2 and control microbiome
– most of the polyphenols shown to be most potent at changing gut flora have been used for centuries as “liver tonics” and “detoxifying herbs” and “liver protectants” or hepatotrophic or trophorestorative herbs, cholagogues and cholerectics. These are all actions important to herbalists when formulating to support detox and liver activity. The new discoveries revolving around the microbiome may give some more insights into their mechanism of action. Words like liver tonic bug the hell out of me as it means nothing, we need to know what, how and why these compounds work to use them most effectively
The take home message
This is all pretty complex! We have about a thousand different bugs, different organs, multiple pH’s and we all eat completely different foods to eat. It is kind of amazing, but the human body has evolved to eat different foods and keep us healthy. What we need to do is eat the healthiest diet we can so as we don’t burden out body with disease. This include a diet rich in plant foods (not grains) which are full of phytonutrients and polyphenols. Obviously flick the junk food and exercise. These are the keys to not only a healthy gut, but a healthy life.
 Paulina Hennig Orcid, Martha Garstkiewicz, Serena Grossi Orcid, Michela Di Filippo, Lars E. French and Hans-Dietmar Beer Int. J. Mol. Sci. 2018, 19(2), 562; The Crosstalk between Nrf2 and Inflammasomes.
 Pond SM, Tozer TN. First-pass elimination. Basic concepts and clinical consequences. Clin Pharmacokinet. 1984 Jan-Feb;9(1):1-25.
 Roberts MS1, Magnusson BM, Burczynski FJ, Weiss M. Clin Pharmacokinet. 2002;41(10):751-90.
Enterohepatic circulation: physiological, pharmacokinetic and clinical implications.