Dr Tuomas Salusjärvi talks here about potential outcomes stemming from the sequenced genome of Lactobacillus GG and their impact on future Gefilus® applications.

Dr Salusjärvi has earned a PhD in biochemistry and spent his entire career working in the food industry. He joined Valio in 2007, attracted by its inventive approach to innovation evidenced for instance by the many pioneering and published studies on e.g. Lactobacillus GG.

The genome map of Lactobacillus GG has given us a better understanding of how the Lactobacillus interacts with the human host, Tuomas explains. We’ve already compared the Lactobacillus rhamnosus GG (ATCC 53103) genome with that of the non-probiotic Lactobacillus rhamnosus LC705 strain. And by overlapping the bacterial genomes we can see the areas that are identical and produce no effect, and those that are different of which some do. There are around 3,000 overlapping genes and fewer than 100 are of real interest.

Going forward, we’ll employ bioinformatics to convert the genes to proteins in the form of computer models and compare those to other known proteins and molecules. The body doesn’t perceive Lactobacillus GG as harmful; it stimulates the immune system which is then ready to attack pathogens. Lactobacillus GG contains compounds that are almost pharmaceutical in nature and encoded by the genes. So a functional food could be used as a substitute for a pharmaceutical product.

Tackling pharmaceutical side effects

We already understand the clinical outcome of Lactobacillus GG e.g. on infant diarrhoea, where immunity towards the relevant pathogens increases, but that’s just a fraction of what Lactobacillus GG can do as 20% of Lactobacillus GG genes are unknown per their action.

Professor Jeremy K. Nicholson, Chair in Biological Chemistry at Imperial College London has described how the super-organism concept may change the medicine of the future. 10% of a human being’s cells are human and 90% are bacteria located in the gut. Many of the side effects of medicines stem from bacterial metabolites. So, looking to the future of probiotics, first a doctor would take a bacterial fingerprint of your gut microbes, showing those that would convert components of a prescribed medicine into something toxic that produces side effects, then direct you to a probiotic treatment to eliminate them. Lactobacillus GG is already proven to decrease diarrhoea resulting from a course of antibiotics.

We still have a lot to learn about the microbiota. There are over 1,000 different species of known gut microbes. We all have a different balance of bacteria in our gut and it’s hard to say what constitutes a normal balance but we can help the individual strike a better balance which is significant since the gut is the body’s most important immunity organ.

In the mood to feel well

The gut is not just a tube in your body with a specific purpose but is well connected to the endocrine and central nervous systems and so acts through the gut-brain axis. Irritable bowel syndrome (IBS), for instance, is considered to be a half gut half psychological problem.

Given that LGG® MAX is a sound treatment for IBS and its effect is proven in published studies, it might be the case that Lactobacillus GG acts on the axis. We could therefore produce mood foods i.e. a probiotic could be designed e.g. to calm you or work as a pick-me-up, or something with a more significant medical application. There is already evidence of a probiotic strain that is able to bind to the opioid and cannabinoid receptors located in the gut, mimicking the effects of morphine and so acting as a local anaesthetic. Probiotics could even be used to improve e.g. cognitive abilities and Valio is following these developments in its work with the scientific communities.

Specialising in Lactobacillus GG

Lactobacillus GG in itself has massive unexploited potential e.g. there is already sufficient evidence to suggest that mothers and their babies could take Lactobacillus GG to prevent the formation of allergies. And Lactobacillus GG could well act in other areas such as relieving headaches.

We have been working with Lactobacillus GG for 25 years as our area of probiotic excellence, know more about it than anyone else and continue to collaborate with all the top researchers. The science of Lactobacillus GG has virtually unlimited long term potential and Valio is at this point simply exploring the short and medium terms to make the base as solid as possible. While we are currently concentrating mostly on Lactobacillus GG, we might take an interest in other probiotics that perform a particular purpose that Lactobacillus GG doesn’t.

Probiotics in other media

Lactic acid bacteria remain active in fresh dairy products that have a relatively short shelf-life and are kept in a refrigerated environment, but it’s much harder to get live bacteria to act properly even in long-life milk because at room temperature the probiotic bacteria either die progressively in what amount to harsh conditions, or make the milk taste off due to their overactivity in it. Genetic engineering would enable scientists to block the genes responsible for the unpleasant flavours or instability, so that probiotics could then be added to other food matrices first before being incorporated into e.g. beverages, frozen foods and cereals, and survive. Functional beverages are just one example of a huge area for development.

We have the technology to do this now but public perception is tilted against the idea of GM probiotic bacteria even though most of the new medicines are produced that way. GM probiotic strains are nevertheless being explored that produce medical compounds when colonising the gut, a kind of cell factory in your gut producing medicines.

Probiotics and prebiotics

Prebiotics act as food for microbes and come in the form of fibres, vegetable components, such as polymeric carbohydrates. They may target a specific group of bacteria that can utilise them, in effect feeding e.g. friendly bacteria such as bifidobacteria. In nature, we can see this where babies’ bifidobacteria is targeted by prebiotics in mother’s milk to increase the bacteria’s volume. In the same way we can add prebiotics to foods which is arguably more effective than supplementing a food with e.g. bifidobacteria.

Prebiotics can also be added to a probiotic to create a symbiotic in which the prebiotic would act as food for e.g. Lactobacillus GG and thus enhance its effect.

Public health savings

Western diseases, such as diabetes type 1 & 2 which like metabolic syndrome is set to explode in the next 20–30 years, other auto immune diseases such as multiple sclerosis, and all the allergies, are connected with disturbed microbiota and gut functions. Microbes affect the permeability of the gut which is essentially too leaky fed on a western diet so antigens from food can pass through to a greater extent than they should. It is considered that this gut leakage is linked to the increase of e.g. allergies and auto-immune diseases. Lactobacillus GG survives the hostile environment of the gut and adheres to it, and so gives us a route to affect some of the unfavourable conditions caused by the western diet and tackle severe conditions that are otherwise incurable.

We can speculate that Lactobacillus GG or other probiotics could actually impact these conditions. Some evidence already exists to the effect that Lactobacillus GG works on allergy formation and if the mechanism were clearer then perhaps we could prevent the formation of e.g. adult onset diabetes. The science is not there yet but it may only be a matter of time. Reductions in the order of just a few percent would save a fortune in public health costs.

Another potential is that since the gut is in effect a pathway that secretes a great many hormones, we could make foods that through the endocrine system would enable you to eat as much as you want but not get fat! This would make rich world countries the main target for licensees.

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