Ellie Mechnikov, the Nobel prize-winning scientist, attributed the health and longevity of the Balkan peasants in the early 20th Century to their habit of drinking fermented milk and the effect of this on the gut flora. He said “When people have learnt how to cultivate a suitable flora in the intestines of children as soon as they are weaned from the breast, the normal life may extend to twice my 70 years”.
The human microbiota is generating a huge amount of interest both in complementary and conventional medicine. Weighing between 1-2 kg, the microbiota which is comprised of bacteria, fungi and viruses, has been described as comparable in influence to an ‘organ’. Ninety percent of the cells in our body are microbes and they contain 150 times more genes than us. Interest is now moving beyond the simple question of which species are present to which genes they carry (“metagenomics”) and which are being expressed – an area that has been termed “metatranscriptomics”. In other words the epigenetics of the microbiome (microbiome = all the genes of our microbiota).
There is a huge amount of research on the functions of the microbiota and also the benefits of probiotics. Well known are the uses of probiotics for the prevention and treatment of antibiotic associated diarrhoea, inflammatory bowel disease, irritable bowel syndrome and other gut related conditions. Perhaps less well known is the research on the uses of probiotics for the prevention of allergies and upper respiratory tract infections, diabetes, non-alcoholic fatty liver disease, autism, atherosclerosis and obesity. This article reviews the functions of the gut bacteria and then looks beyond their well reported effects in relation to the gut, towards research that is being done in the area of obesity.
Functions of the microbiota
A healthy microbiota performs many beneficial functions:
- Immune stimulation and modulation. For example, research has shown that regularly taking a probiotic stimulates sIgA production, an antibody found in all the mucosal surfaces of the body. Studies have shown probiotics to be effective in reducing the frequency and duration of upper respiratory tract infections. Probiotics also modulate the immune response and reduce hay-fever and allergic symptoms.
- Digestion of food – for example Lactobacillus spp which break down lactose in foods and Bifidobacteria which digest fibre.
- Production of some vitamins eg B vitamins and vitamin K. And low levels of Bifidobacteria have been linked to low B12 levels.
- Production of Short Chain Fatty Acids, such as butyrate, which keep the gut lining healthy.
- Protection from pathogens. Through a number of mechanisms, including competitive inhibition, beneficial microbes inhibit the overgrowth of pathogens.
- Metabolism of cholesterol and bile acids, thus contributing to lowering cholesterol levels in the body and recycling of bile acids.
The microbiota also play a role in the metabolism of potentially harmful substances such as nitrosamines, heterocyclic amines and in the sequestering and removal of heavy metals from the body. On the other hand the microbiota may also be a source of antigens (eg Lipopolysaccharides – LPS), harmful compounds and pathogens. An overgrowth of potential pathogens is referred to as a dysbiosis. The consequences of dysbiosis may be leaky gut and lead to the occurrence of intestinal and systemic disorders.
Colonisation after birth
The colonisation of the human gastrointestinal tract begins before and during birth, as the baby passes through the birth canal. Early colonisation is influenced by the environment, food, mother/child diseases and drug use, in particular antibiotics. An intensive phase of colonisation of bacteria in the human gastrointestinal tract usually lasts until two years of age after which the child’s gut microbiota begins to resemble that of an adult’s. As we age the composition of bacteria changes and there is a significant reduction in the quantity of Bacteroides and Bifidobacteria, with Clostridium, Eubacterium and Fusobacterium starting to dominate.
The various species of bacteria fall predominantly into 2 phyla – Firmicutes and Bacteroidetes which together account for more than 90% of the total population of the intestinal microbiota.
Link with Obesity
Many studies have shown that obesity is associated with significant changes in the composition of the intestinal microbiota. It is recognised that the balance of Bacteroidetes and Firmicutes in the intestine is important. A higher ratio of Firmicutes to Bacteroidetes is strongly associated with inflammation and obesity. African populations have a gut dominated by Bacteroidetes, Western populations by Firmicutes.
This difference in ratios has also been demonstrated in mice – Bacteroidetes is significantly lower in obese mice (20%) compared to normal weight mice (40%). In a 2013 study, gut bacteria were transferred from an obese human twin into the gastrointestinal tract of slender mice and the mice grew fat. When bacteria from the thin twin were introduced into the lean mice the mice stayed lean so long as the animals ate a healthy diet low in fat and high in plant matter.
This is also seen in humans and the so-called western-style high fat, low fibre diet dramatically impacts the intestinal microbiotia. The composition of the microbiota of lean and obese people differs with a higher ratio of Firmicutes to Bacteroidetes in obese people. This ratio can be altered with diet induced weight loss. For example, in a small study of obese individuals a change of diet to low fat and increased vegetables resulted in a decline in Firmicutes and an increase of Bacteroidetes of up to 20%.
However the obesity associated link between the ratio of Bacteroidetes to Firmicutes remains controversial as it has not been repeated in all studies and may be an oversimplification. It is not clear whether it is the mechanisms associated with obesity or dietary fat intake that has an effect on the microbiota.
Multiple studies have demonstrated that a high fat diet can trigger inflammation. Other studies have demonstrated that germ-free mice do not gain weight on a high fat diet or a regular diet of the same caloric content. Whereas, in mice with gut bacteria a high fat diet promotes obesity. In other words, obesity and associated inflammation only occur in the presence of gut bacteria.
The impact of the gut microbiota on the development of obesity is not yet fully known but a number of mechanisms related to inflammation have been proposed, including:
Obesity is associated with elevated serum levels of lipopolysaccharide (LPS), also referred to as endotoxin, which is a component of the cell wall of Gram negative bacteria. Intravenous administration of LPS in mice resulted in the development of insulin resistance and weight gain. Insulin resistance results in high circulating insulin levels. Insulin is a hormone that promotes fat synthesis and storage.
High levels of circulating LPS are associated with inflammation, dysbiosis and leaky gut and a high saturated fat diet has been observed to increase plasma levels of LPS. So fat contained in food may be an important regulator of the concentration of LPS. The introduction of four weeks of high fat diets in mice resulted in 2-3 x increase in plasma levels of LPS. This has been confirmed in people with obesity and type 2 diabetes.
It is believed that the high saturated fat diet allows LPS to enter the circulation more readily, increased plasma LPS has a detrimental effect on glucose metabolism and altering the microbiota can alleviate endotoxemia and insulin resistance. Thus the evidence suggests that LPS plays a criticial role in the development of obesity and associated insulin resistance and low-grade inflammation.
A high fat diet is associated with decreased levels of Bifidobacteria. Fermentation of prebiotic fibre by Bifidobacteria produces short chain fatty acids (eg butyrate etc), which positively effect gut barrier function (ie reduce leakiness). Therefore by stimulating the growth of Bifidobacteria it is possible to lower endotoxemia and improve or avoid metabolic disturbance. A reduction of LPS by prebiotic treatment significantly enhanced glucose tolerance and inflammatory markers in the liver of mice fed a high fat diet.
Fasting induced adipose factor (FIAF)
Another potential factor linking gut microbiota to obesity is blocking the expression of fasting-induced adipose factor (FIAF) by the microbiota. FIAF inhibits the activity of lipoprotein lipase (LPL) an enzyme responsible for the storage of energy in fat. The decreased expression of FIAF determines increased LPL activity and enhances the process of storing energy in the form of fat.
Cultivating a better microbiome
Since it has been shown that gut microorganisms have a role in obesity through a number of mechanisms, modulation of the microbiota is a potential tool in the prevention and treatment of obesity and a number of diet books targeting the gut have been published recently. Dietary and supplement therapy to cultivate a better microbiome:
Eat fermented foods – live plain yoghurt, kefir (water or dairy), Kombucha (fermented tea) and fermented vegetables (eg kimchi and sauerkraut). These can all be made at home or purchased ready-made. If using the latter, watch for added ingredients and that the products have not been pasteurised. Kefir grains and Kombucha scobys can be purchased from health food shops or online. Kefir is similar to yoghurt but the grains are a mix of bacteria and yeast.
Enjoy red wine, tea, coffee and chocolate (in moderation). The polyphenols in these foods are being researched for their ability to positively influence gut microbial diversity. The polyphenols in black tea have been shown to increase Bifidobacteria. Green tea has also been shown to increase Bifidobacteria and at the same time reduce levels of potentially harmful Clostridia species. High intake of flavonoids from cocoa for 4 weeks increased Bifidobacteria, Lactobacilli and decreased Clostridia. These changes in gut bacteria were accompanied by a reduction in the inflammatory marker C-reactive protein. Interestingly, in the cocoa study Clostridium histolyticum in particular was reduced – this is among the species of Clostridia found to be increased in the stool of autistic children. Levels of endotoxin (LPS) are dramatically reduced in individuals who consumed red wine in moderation – one small glass per day. On the other hand, a higher alcohol consumption is associated with increased levels of LPS.
Prebiotic foods – FAO/WHO defines prebiotic as “non digestible food ingredients that beneficially affect the host by selectively stimulating the growth and / or activity of one or a limited number of bacterial species already established in the colon and thus improve the host’s health”. It has been estimated that the typical hunter gatherer in our distant past consumed as much as 135 g of inulin each day. Prebiotics occur in vegetables and are especially high in chicory, Jerusalem artichoke, garlic, onions and leeks. Prebiotics reduce levels of LPS and consuming large amounts of polysaccharides can change the composition of the microbiota and its metabolic functions within 4 weeks.
Drink filtered water – chlorine in tap water may have an adverse effect on gut bacteria so filter your water with a jug or under the sink unit. Under the sink filtration systems are now very affordable.
Take a daily Live Bacteria supplement – There are thousands of different species of bacteria that make up the human microbiome but some important ones have been identified and studied in both animals and humans. Different strains provide different benefits so it is important to choose a multistrain product rather than one with just one or two strains. An in vitro study by Borthakur (et al) 2013 illustrates this. Gut cells were pre-treated with one of four strains of Lactobacillus – ie one of the following: Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus or Lactobacillus casei. The gut cells were then exposed to an inflammatory agent called Platelet Activating Factor (PAF). Inflammation was not triggered in cells that had been treated with Lactobacillus acidophilus or Lactobacillus rhamnosus – in other words these species had a protective effect. However, Lactobacillus casei and Lactobacillus plantarum did not show a protective effect with this particular agent. There are many other studies showing the benefits of L plantarum and L casei – this study just demonstrates the benefits of choosing a multistrain rather than a one or two strain product.
David Perlmutter in his recent book Brain Maker also talks about applying probiotics via enema and gives a step by step protocol.
Consider L-glutamine – oral supplementation with l-glutamine altered the composition of the gut microbiota in overweight and obese individuals reducing the Firmicutes to Bacteroidetes ratio, which resembled weight loss programmes.
Although the relationship between the gut microbiome and obesity is not fully understood, one mechanism at least is clear – endotoxin from the gut can trigger inflammation and insulin resistance and this is related to weight gain as well as the development of other health conditions. Therefore, a focus on cultivating a healthy microbiome is an area to include as part of a weight management programme.
Barczynska R et al (2015) – Intestinal microbiota, obesity and prebiotics. Polish Journal of Microbiology, 64, 2, 93-100
Perlmutter D with Kristin Loberg (2015) – Brain Maker . Hodder & Stoughton Ltd, London.
Borthakur A et al (2013) – Lactobacillus acidophilus alleviates platelet-activating factor-induced inflammatory responses in human intestinal epithelial cells. PLOS ONE, 8, 10.
If you have any questions regarding the health topics that have been raised, or any other health matters please do contact me (Clare) by phone or email at any time.
[email protected], 01684 310099
Amanda Williams and the Cytoplan Editorial Team: Joseph Forsyth, Simon Holdcroft and Clare Daley