Part 3: Manipulating the Microbiome

by Hidaya Aliouche

You can catch up on the first blog here and you can read the second blog here

The rapid increase in obesity prevalence has expanded the therapeutic horizon. Part 3 explores the range of weird and wonderful solutions the market has to offer. Can we force the microbial hand simply through our dietary choices? Do the plethora of probiotic and prebiotics that saturate the market live up to their claims – or does the answer lie at the other end of the digestive system, found in our faeces? 

The most profitable areas for the pharma industry are the prebiotic and probiotic segment which now fuels a global market projected to grow by £48bn by 2023. The support of probiotics in the prevention of obesity has been explored in this piece by two studies, but there are countless others that have consistently shown their preventative role against obesity, and associated metabolic disorders, and inflammation. First, let’s assess the benefit of probiotics in weight loss, a highly popular supplement that feature heavily in supermarkets across the world.

Figure 1. ‘Do probiotics –whether dairy based or neatly packaged in pills – really possess the power to restore the gut microbiome? Yoghurt’ by Jules is licenced under CC BY 2.0.

Probiotics are typically available either as pills or as milk and yoghurt-based drinks. Their effectiveness has faced much scepticism, stemming largely from their added extras – particularly the worryingly high amounts of sugar, and very small numbers of probiotic strains. Any benefit provided by the probiotic is questionable as typical serving sizes contain probiotic numbers that are several orders of magnitude smaller than the number of bacteria already present in our gut; probiotics are essentially a drop in a bucket.  Moreover, effective colonisation of the gut is small as probiotics are unlikely to survive the highly acidic environment of the stomach on their journey to the gut. Providing some species did survive, colonisation is dependent on survival of the fittest strain – probiotics are poor matches for the highly adapted species of bacteria that have held long-established posts in our gut.  Paired with high sugar contents, the net effect is more likely to increase your predisposition to diabetes. Other criticisms relate to the choice of probiotic strains in such products; many studies have reported that only very specific Lactobacillus or Bifidobacterium strains are effective at combating obesity. Not all strains are equally able to induce fat loss or improve metabolism. This issue is compounded further by the lack of transparent reporting of bacterial strains used in the products; many are patented strains which makes their true nature difficult to discern. Taking these issues into consideration, the bottom line is that milk- and yoghurt-based probiotics are ineffective manipulators of your gut microbiome. There could be a case for taking higher quality probiotic pills as they skirt the issue of sugar and are more transparent in communicating the identities of specific strains. Yet the numbers of bacteria are small and issues relating to effective colonisation still stand. They are also considerably expensive, costing anywhere between £9-£32.

Prebiotics, then, may offer a more effective means of manipulating our microbiome as they can reach our gut efficiently. Prebiotics are available in two forms; foods and supplements. The optimal prebiotic foods include kimchi, sauerkraut, whole-grains, lentils, fruits and vegetables. We have discussed how Firmicutes is lower in individuals with obesity than in lean people, and studies have supported the notion that other species such as Bifidobacteria are also lower. The dietary fibres can expand their populations, which in turn improve metabolism and reduce fat mass. Interestingly, the prebiotic approach has been shown to prevent the expression of genes that are related to weight-gain and inflammation and stimulate the release of gut hormones that decrease our appetites and boost our satiation. In principle, pill- delivered prebiotics can do the same, but they fail to pack the same micronutrient punch as foods, lack in taste and are considerably more expensive. The choice is evident – switching your diet to one that is dominated by naturally-sourced prebiotics is an effective means of transforming your gut microbiome, improving gut health, decreasing your fat mass and improving metabolism.

Figure 2. We can support healthy bacteria also called probiotics, such as Lactobacillus and Bifidobacteria in our gut by eating fermented food like kimchi and soluble-fibre rich foods such as whole grains, fruit and vegetables.

Celebrities have also been in the pursuit of capitalising on the intriguing discoveries of the microbiome. Sites such as Gwyneth Paltrow’s “GOOP”, amongst a host of others, suggest that colonic irrigation is a holy grail for gut problems. Colonic irrigation involves pumping 60 litres of water through a tube inserted into the rectum where it reaches the bowel and waste products are then flushed out. A variant of the irrigation is the coffee enema, which hit the headlines early this year, with the endorsement of one of many systems, the ‘Implant-O-Rama’ by a Doctor Junger. Junger is one of many professionals who have alternative lifestyle practices on the internet. Many like him suggest they can help you lose weight; however, several comprehensive reviews of the procedure have shown there is little evidence to support this claim. More likely effects of the treatment include bowel perforation, renal failure, electrolyte imbalance and abdominal pain to name a few. In addition, your microbiota is going to suffer – according to a 2014 study from the University of Helsinki, a 31-fold decrease in the bacteria living in the colon can result. One can conclude that colonic irrigation should be avoided at all costs.

Faecal microbiota transplantation is the latest therapeutic approach to alter the microbiome. Historically, FMT has been traced back to ancient China, where administration of a broth prepared from dried or fermented stool from a healthy person was used to treat diarrhoea. The concept of FMT has persisted, but fortunately the administration method in clinical settings of the 21^st century is quite literally an easy pill to swallow. FMT is an effective treatment for gut infections, particularly Clostridium difficile, and evidence has pointed to success in individuals suffering from intestinal chronic inflammatory diseases. The mechanism underlying the success of FMT is yet to be elucidated; nonetheless the process is thought to be a re-population of gut microbiota in the patient with the healthy microbiota of a donor that restores a functional gut microbiota compartment.

Concerning the treatment of obesity with FMT, the first transplant of human faeces into germ-free mice was performed by Ridaura et al. in 2013. Microbiota from discordant twins for obesity (one was lean whilst the other was obese) were transplanted into adult germ-free mice.  The outcome mirrored that of the Gordon et al., study; the recipients adopted the traits of their donors. Furthermore, the two sets of colonised mice were co-housed. This enabled coprophagia – the ingestion of faecal matter- causing the obese mice microbiota to become colonised with the lean mouse microbiota. The effects were impressive, with the obese mice adopting the lean physiques and metabolic features of their cage-mates. Studies in Humans have corroborated these findings – a case published in the new journal Open Forum Infectious Diseases reported a case of weight gain in a patient who was successfully treated with FMT for a C. difficile infection after receiving stool from an overweight donor. These studies, amongst many others are certainly provocative starting points for the therapeutic application for FMT. Be warned, with these studies still in their infancy, a plethora of do-it-yourself YouTube videos have emerged…involving your kitchen blender. If you are tempted to whip yourself up a shake, consider the high risk of blood- and stool- borne diseases that you could give yourself, ranging from salmonella to HIV.

Presently, a clinical trial is underway in Boston, Massachusetts hoping to determine the impacts of FMT in patients with obesity. This is crucial as there are multiple unknowns associated with FMT p

rocedures, including selection of eligible donors and recipients and protocols for performing FMT. The latter point is particularly important as stool can be difficult to characterize and invariably changes every time it’s produced.  Nonetheless, the science behind FMT is burgeoning. Of course, until the results of large randomized, controlled studies are published, and clinical guidelines are firmly in place, the elusive fat-busting “poop-pill” remains a dream.

 

Presently, a clinical trial is underway in Boston, Massachusetts hoping to determine the impacts of FMT in patients with obesity. This is crucial as there are multiple unknowns associated with FMT procedures, including selection of eligible donors and recipients and protocols for performing FMT. The latter point is particularly important as stool can be difficult to characterize and invariably changes every time it’s produced.  Nonetheless, the science behind FMT is burgeoning. Of course, until the results of large randomized, controlled studies are published, and clinical guidelines are firmly in place, the elusive fat-busting “poop-pill” remains a dream.

 

Research indicates that diet is the simplest and most successful manner of manipulating our microbiota to our advantage. However, the quest for a better understanding of the microbiota and their function before we can attempt to manipulate it, is far from complete. In the meantime, perhaps participate in the next Veganuary?

 

 

 

•   Turnbaugh, P.J., Bäckhed, F., Fulton, L. & Gordon, J.I. (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host and Microbe 3, 213-223.
• Turnbaugh, P.J., Ley, R.E., Mahowald, M.A., Magrini, V., Mardis, E.R. & Gordon, J.I. (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–103.
• Ridaura, V., Faith, J., Rey, F., Cheng, J., Duncan, A., Kau, A., Griffin, N., Lombard, V., Henrissat, B., Bain, J., Muehlbauer, M., Ilkayeva, O., Semenkovich, C., Funai, K., Hayashi, D., Lyle, B., Martini, M., Ursell, L., Clemente, J., Van Treuren, W., Walters, W., Knight, R., Newgard, C., Heath, A. & Gordon, J. (2013) Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice. Science 341, 1241214-1241214.
• Schroeder, B., Birchenough, G., Ståhlman, M., Arike, L., Johansson, M., Hansson, G. & Bäckhed, F. (2018) Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration. Cell Host & Microbe 23, 27-40.
• Valiquette, L., Sirard, S. & Laupland, K. (2014) A Microbiological Explanation for the Obesity Pandemic? Can. J. Infect. Dis. Med. Microbiol. 25, 294-295.
• Youngster, I., Russell, G., Pindar, C., Sauk, J. & Hohmann, E. (2014) Oral, Frozen Fecal Microbiota Capsules for Relapsing Clostridium difficile Infection. JAMA 312, 1772-1778.
• Zou, J., Chassaing, B., Singh, V., Pellizzon, M., Ricci, M., Fythe, M., Kumar, M. & Gewirtz, A. (2018) Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health. Cell Host Microbe 23, 41-53.e4.

About Me

I am a postgraduate student at the University of Manchester.  Having completed a degree in Biochemistry I am now pursuing a career in the field of science and medical communications. In my spare time you can find me sweating it out outdoors, crocheting in a corner and baking up a storm (not necessarily in that order…or at the same time)