Toxins that come from the gut

This column is written by Stig Bengmark – Professor Emeritus, scientist, lecturer and writer. Read more of Stig Bengmark’s columns here.

In several previous columns, I’ve touched on various toxins and their negative effects on the body. Among other things, I’ve devoted an entire column to external toxins plus also my extensive column on the toxins we produce when we expose food to high temperatures – known as A.G.E. and A.L.E. Today it’s going to be about some other toxins – those that come from the gut. My main interest in the latter is in inflammation, which is created in the intestine and which leads to chronic diseases. I am very keen to spread the knowledge that I’ve accumulated over many years of research. This column will specifically deal with inflammation, toxins formed in the gut, as well as kidneys, and dialysis.

Bad bacteria are experts in making toxins

I often come back to the topic of the importance of taking care of the good bacteria in our gut. When we don’t take care of our good bacteria well enough, they disappear/lose their dominance in the gut and allow the bad, disease-causing gut bacteria to take over large parts of the gut flora. There are consequences, and all the disadvantages of a poorly functioning gut flora (dysbiosis) appear quickly – for all of us, but above all for vulnerable groups such as those with chronic kidney disease, and especially those who have regular dialysis treatments and who have severely impaired immune functions.

The main responsibility for our health lies with our microbiota

The 1.5 kg of bacteria that we have in our gut, the microbiota, needs to be managed with, among other things, a daily supply of food that the good bacteria need for their growth and continued existence (lots of fruit and veg – preferably raw – and a lot of magnesium). Unfortunately, in modern times people don’t eat this type of food to a sufficient extent. Most people instead rely on factory-made food and refined diets such as bread, pizza, pasta, cooked rice and cooked root vegetables – food that’s absorbed early on in the upper small intestine and of which only a small proportion reaches the large intestine where the ‘hungry’ healthy bacteria are found. This type of food is definitely not food for bacteria. With this type of bad diet, the intestinal flora quickly takes a negative turn, the good bacteria leave voluntarily and let the bad bacteria take over to dominate the gut.

The microbiota’s speciality – breaking down proteins and eliminating protein-bound toxins

The gut flora (the microbiota) has several important tasks. It helps, among other things, to extract different types of nutrition from plants and, for that matter, also from foods that come from animals: nutrients, antioxidants, and vitamins. Another important task for the microbiota is to efficiently contribute to the breakdown of consumed proteins – a very important specialty. Degradation of proteins always entails a certain release of so-called uremic toxins, which are a major burden on our kidneys for all of us, and not least people with severe kidney disease. A properly-functioning microbiota can effectively facilitate both the breakdown and elimination of these uremic toxins – a property that would be of more use to kidney patients, especially as this is an area where dialysis treatment is lacking.

A properly-functioning microbiota is expected to radically reduce inflammation in the body, increase the effectiveness of one’s own immune system, and indirectly protect against recurrent infections, chronic diseases and premature ageing. Patients suffering from chronic diseases such as Alzheimer’s disease, ADHD, diabetes, chronic lung disease (COPD), chronic liver disease and chronic kidney disease (often called ESRD – end stage renal disease – hereafter referred to as dialysis patients), never have a properly-functioning microbiota and need to be given a daily supplement of synbiotics (a combination of prebiotic fibre and specific lactobacilli/probiotics.)

Dialysis patients do not have the protection the microbiota gives

Like patients with chronic liver disease, chronic lung disease, Alzheimer’s, diabetes and HIV patients, dialysis patients have a poorly functioning immune system and suffer from high pressure from chronic inflammation. Dialysis is an effective method of eliminating many of the toxins that are formed daily in our body, but it has its limitations and is far from as effective as one would like. Daily consumption of effective synbiotic products could be an effective complement to processes such as:
• Elimination of uremic toxins
• Elimination of the bacterial toxin endotoxin
• Elimination of all other external toxins hormone residues, drug residues etc.

Patients with chronic kidney disease are often advised to be cautious with fruit, for example, mostly to counteract an excess of potassium that can easily occur in kidney patients. One disadvantage with this is, naturally, that this also limits the supply of other nutrients – antioxidants and minerals, mainly magnesium (but also short fatty acids, which are vitally important for the growth and multiplication of the good bacteria in the gut as well as to prevent leakage of toxins through the intestinal wall).

Disease-causing intestinal bacteria are common among kidney disease patients treated with dialysis

It’s well known that dialysis patients suffer from a high level of so-called oxidative stress, which creates the conditions for cardiovascular disease, metabolic syndrome, weight loss/anorexia, anaemia and other complications. Even chronic fatigue is especially common among this group. Not only uremic toxins but some or all of the intestinal bacteria are often found in the blood of dialysis patients – in a recently published study, the DNA of disease-causing intestinal bacteria was found in no less than 20% of dialysis patients (Wang F et al. Nephrology 2012; 17: 733-738).

Often, malignant bacteria such as Klebsiella spp, Proteus spp, Escherichia spp, Enterobacter spp, and Pseudomonas spp are also found in the blood of dialysis patients, in parallel with signs of an extra increase in inflammation in the body and impaired metabolism: increased levels of D-lactate in plasma, increased C-reactive protein and increased interleukin-6 – the latter a specific sign of increased inflammation in the body.

The biggest problem – accumulation of waste products

Identifying and eliminating ‘organic waste products’ is the main goal of dialysis. Between 90 and 100 of these ‘waste products’ have been identified. The majority of these come from the breakdown of amino acids (not least tryptophan and tyrosine), which are often ingested in far greater amounts than what the body needs and which are also poorly broken down if the gut flora is functioning poorly (which it always is with dialysis patients). Tryptophan and tyrosine are found in large amounts in seeds, nuts, different meats, cheese, shellfish, fish, and eggs. And tyrosine is also found in large amounts in seaweed (spirulina).

Dysbiosis and leaky gut

Leakage of bacterial toxins such as indoxyl sulphate and p-cresol sulphate has been reported to be significantly higher in patients undergoing haemodialysis than in those undergoing regular peritoneal dialysis (Pham NM et al. Clin J Am Soc Nephrol 2008;3:85–90).

The gut problems among kidney patients have been known about for decades and, with this in mind, it’s absolutely inconceivable that so few attempts have been made to recondition the gut, reduce the production of toxins, and stop the leakage of bacterial toxins into the body. So, it’s particularly gratifying that recently published studies show that the addition of prebiotic fibre in amounts as small as 10-20 grams per day, significantly reduces the amount of the bacterial toxin p-cresol sulphate in the blood (Meijers BK et al. Nephrol Dial Transplant 2009;25:219–224). This should stimulate further studies – the synbiotic composition that I’ve been working with daily for over 15 years contains 10 g of specific prebiotic fibre.

Probiotics have significant effects for dialysis patients

Back in the infancy of the probiotic era, a small study was done with promising results. Eight haemodialysis patients were given Lactobacillus Acidophilus, a lactobacillus which is very commonly found in yoghurt. The treatment effectively reduced the toxin, dimethylamine (DMA), in the blood from an average of 224 to an average of 154 micrograms/dl (p <0.001) (Simenhoff ML Miner Electrolyte Metab 1996; 22: 92-96). One remarkably important observation was that, at the same time, it was possible to observe a 50% reduction of the carcinogenic poison, Nitrosodimethylamine, in the blood (from an average of 178 to an average of 83 ng/kg). You would think that these observations would stimulate a flood of studies using more specific probiotics and synbiotics, but this unfortunately did not happen.

A newly-awoken interest

It would take 15 years before the next study was published, this time also too small a dose of lactobacilli was used, and it was carried out on too few patients (9) and also for a too short period (2 weeks). This time they tried a synbiotic composition – 10^8 Lactobacillus casei strain Shirota, 10^8  Bifidobacterium breve, (Yakult) and just 4 g of galacto-oligosaccharides – a well-known prebiotic. Despite all the disadvantages of the way the study was performed, significantly lower blood levels of the toxin, p-cresol, were reported, as well as a reduced degree of constipation (Nakabayashi I et al. Nephrol Dial Transplant 2011;26:1094-1098).

A meta-analysis shows unique possibilities with treatment with pre-, pro-, and synbiotics on dialysis patients

As early as the following year, 2012, the first meta-analysis was published – an analysis of everything published up to this date on the supply of pre-, pro- and synbiotics to dialysis patients. This states, as already pointed out above, that the observations in each individual study are based on far too few patients, too low doses of lactobacilli and far too short study periods, but that, despite this, there are strong indications that synbiotic treatment effectively reduces blood levels of the bacterial toxins indoxyl sulphate and p-cresol sulphate (Rossi M et al. Int J Nephrol 2012;2012:673631).

In 2013, 16 Korean children with kidney disease were treated with the well-known Italian probiotic composition VSL # 3 (consisting of eight different high-dose good bacteria) for a 12-week study. The levels in the blood of indoxyl sulphate and p-cresyl sulphate were measured after 4, 8 and 12 weeks, but unfortunately no effect could be demonstrated (Hyun HS et al Korean J Pediatr 2013; 56: 159-164) – unfortunately VSL has often been shown to be ineffective in various situations.

Pro- and synbiotics are effective at ‘beating down’ inflammation

This year, a Taiwanese study was published which offers a lot of hope. In this study, over 6 months, 39 patients were given either a probiotic composition (consisting of a billion parts of three different bifidobacteria plus one billion parts of Lactobacillus plantarum A87) to be compared with maltodextrin as a placebo.

A number of inflammation-indicating markers (cytokines) and endotoxins were measured before and after the end of treatment and showed significant improvements in the group treated with the probiotic. Renal function specifically was better preserved in the group treated with the probiotic (Wang IK et al Benef Microbes. 2015 E-pub). It’s important to point out that this study is also based on too little patient material, and that this probiotic composition did not contain any added fibre, and above all that it contained far too small an amount of lactobacilli – I myself am working with much, much larger doses.

Synbiotic treatment is an excellent complement to dialysis

New filters have enabled evermore effective dialysis treatments, but significant problems remain, not least with regard to the effective elimination of azotemic toxins (nitrogen-containing substances), and unusual substances which are highly protein-bound (Davenport A Hemodial Int.2014 Oct;18 Suppl 1:S43-7). The ability of dialysis to eliminate these is far from satisfactory. These substances include, among others, P-cresol, which is particularly associated with a high degree of inflammation, an increased degree of cardiovascular disease in non-diabetics, and increased mortality rate among dialysis patients (Krieter DH et al Nephrol Dial Transplant 2010; 25: 212–21, Sirich TL et al. Semin Nephrol. 2014 Mar;34(2):106-17). It’s important to note that synbiotic treatments have great potential to eliminate the often-observed, very painful fatigue among dialysis and sometimes transplant patients.

According to Sirich et al (Sirich TL. Semin Dial. 2015;28:75-80, Sirich TL et al Clin J Am Soc Nephrol. 2014;9:1603-1610. Sirich TL et al Semin Nephrol. 2014;34:106-117) there are also a number of almost unidentifiable protein-bound toxins, which dialysis eliminates poorly and whose clinical effects are far from clear, and which may well have even greater negative effects in the body than even pCS. Synbiotic treatment offers great opportunities for eliminating exactly these protein-bound toxins and thereby offers a significant complement to an otherwise successful dialysis treatment for end-stage kidney disease.

Kidney care is an impenetrable fortress

In two groups of patients, it’s been shown that it’s almost impossible to carry out clinical studies with synbiotics – patients with HIV and kidney disease. Here, business seems to be guarding its territories very well indeed. In the end, I received permission to do a small study on HIV in California, but for at least 15 years I’ve been wanting to do clinical studies with Synbiotics on chronically ill patients – but I have not succeeded. I’ve visited, lectured to, and tried to motivate kidney doctors around the world – from leading clinics in Stockholm and London to developing countries – with no success. There’s been no lack of enthusiasm among kidney doctors, but at the ‘last minute’ there’s always some pharmaceutical company, for example, willing to pay large sums for ‘an absolutely necessary’ trial of a new drug, a new filter, or the like.

Can anyone tell me how to proceed with this?

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