Benjamin Seeks to Improve Gut Health with Bacterial Lysate

Benjamin leads his own research group, the Jensen Group, at the department. The group, which is part of the Endocrinology and Metabolism research theme, studies how the bacteria in our guts interact with other parts of our body and how this "conversation" is influenced by what we eat.

They focus particularly on how the gut barrier, whose (dys)function is related to a host of diseases, is affected by this interaction. They are especially interested in how diet plays a role in both initiating, preventing, and treating chronic inflammatory diseases in the body.

Creating a better understanding of the gut barrier

The gut barrier is essentially a membrane of mucus and cells lining the inside of our intestinal walls. It plays a crucial role in preventing harmful substances, such as bacteria and toxins, from entering our body through food and making us sick. At the same time, it is essential for allowing the passage of important nutrients from digested food that our body needs to function. 

A vital function of the gut barrier is its cooperation with the local immune system in the gut. Nearly 70% of the body's immune system is found in the gut, and the proper collaboration between the gut barrier and the immune system helps identify and combat potential threats that may slip through, while remaining tolerant of the bacteria and other components that are meant to be there. When the gut barrier does not function properly, it can lead to increased permeability, also known as leakage or leaky gut. Leaks allow unwanted substances to pass through, contributing to the development of inflammatory diseases both locally in the gut and elsewhere in the body, leading to significant health problems. 

Many people are familiar with diseases such as Crohn's and Colitis, which can be extremely debilitating, but obesity is also characterized by increased gut permeability. Treating the gut barrier therefore has great potential; both in treating inflammatory bowel diseases and in treating the associated diseases that come with obesity, where chronic low-grade inflammation increases the risk of health complications such as diabetes, cardiovascular diseases, and fatty liver disease.

In Benjamin's group, they specifically focus on how diet affects this gut barrier. They aim to understand how certain components in the diet can strengthen or weaken the barrier. This work can help clarify how our dietary choices can play a role in affecting our body's ability to manage inflammation and disease, and how dietary choices can interact with supplements such as probiotics. Benjamin elaborates:

The past two decades of research have shown that the bacterial composition in our guts significantly affects our susceptibility or resistance to disease development. Despite significant progress, moving from basic descriptions of what is there and subsequent observations of specific associations (which bacteria are found in high levels in certain types of diseases) to now gradually finding causal relationships (which bacteria can affect what), we still know very little about how to manipulate these interactions in a controlled and predictable way.

However, as bacteria are living organisms, it is evident that diet and the local microenvironment in our individual guts significantly affect how each bacterium behaves. In other words, instead of just changing the composition of bacteria, there may be great potential in changing the behavior of individual bacteria. For example, we can consider our gut bacteria as a classroom. Under the wrong circumstances, even the sweetest child can become a bad version of themselves, while the right circumstances can make even the most challenged student flourish. So instead of swapping out and discarding bacteria, we might want to change how we "talk" to them.

Feeding our gut microbiome

Benjamin and his group are particularly interested in a bacterium called M. capsulatus Bath. It is not naturally found in the gut but in soil, where it lives on methane. It may not sound like something you would want to ingest voluntarily, and it does require some processing before consumption. The group conducted an experiment where they cultivated a large number of these bacteria, which were then processed in a manner quite similar to making French press coffee. The final product, called bacterial lysate, consists of inactive and dead bacteria with a high protein content, an essential part of the diet for humans and most animals. 

The proteins were given to a group of mice that had been fattened up and were on a diet high in fat and sugar, resembling a Western fast food diet. The mice, on the brink of developing diabetes, were then given bacterial protein instead of either plant protein (soy protein) or animal protein from milk and meat. They experienced a significant health change. The mice's metabolism greatly improved within a few weeks, and they showed modest improvement in insulin sensitivity and greater glucose tolerance. They were no longer at risk of developing diabetes. Their weight also stabilized, and the mucus layer in their intestines (and thus their health condition) significantly improved. Remarkably, only the protein source was changed, while the mice still consumed a considerable amount of sugar and carbohydrates. There was something in the bacterial protein that had a remarkable effect.

It seems that this soil bacterium has unique, biologically active components with enormous health-promoting potential. By replacing the protein source with this bacterial lysate, we see a change in the gut microbiome (bacteria and their products) towards what can be characterized as healthy, and we see an exceptional induction of some regulatory T cells, known to play a significant role in maintaining a healthy gut environment by reducing both acute inflammation (such as colitis) and chronic low-grade inflammation (such as in obese individuals).

In addition to the aforementioned effects, the bacterial lysate also increases gut tightness, partly by stimulating a better and healthier mucus layer in the colon. We observe this in diet-induced obese mice, experimentally induced colitis mice, and even mice with chemotherapy-induced damage in the small intestine, which is a known side effect of current cancer treatments. This bacterial lysate, therefore, appears to have considerable potential to normalize a dysbiotic gut barrier in a wide range of different but very clinically relevant indications.

However, more research is needed to identify the bioactive molecules at play in the bacterial lysate. Once identified, they can be tested as dietary supplements for human consumption. This could prove to be significant for people with various bowel diseases, which today can only be treated symptomatically, if a treatment could help mitigate or even cure the disease itself. It could also possibly contribute to lasting weight loss and increased health in people who have lost weight either medically or through lifestyle changes, where maintaining the achieved weight loss can be very difficult.

We see great potential in this bacterial lysate, but continued research is needed to identify the biologically active fractions, so a sustainable dietary supplement can be developed to support lasting weight loss and reduce gut-related discomfort.

The significant treatment perspectives lie in identifying the active component(s) that can increase the occurrence of regulatory T cells in both the small and large intestine and improve gut barrier functionality. The sum of this could contribute to developing a drug with the potential to treat the underlying cause of many gut-related disorders, representing a milestone in the medical treatment of these complications.

Growing bacteria could help mitigate climate change

There are significant health perspectives in Benjamin and his group's research. But there is more to gain in other areas as well, namely using the findings to mitigate climate change. As mentioned earlier, the bacteria live on methane, a potent greenhouse gas and a byproduct of various industrial processes. Instead of releasing methane into the atmosphere, it can be used as food for the bacteria, which can then be converted into food for animals and humans.

In other words, it is an extremely climate-friendly way to produce protein, not only because the bacteria are fed a greenhouse gas that would otherwise contribute to global warming, but also because it requires far less space than other production methods. Compared to plant-based protein production, which is already space-efficient compared to production of animal protein, bacterial protein production occupies 0.03% of the area as it is grown in large, vertical tanks. This means many fields now used to grow plants could be given back to nature for the benefit of both climate, environment, and humans.

Bacteria can promote health while producing bacterial protein is much more sustainable than protein from animals and even plants. If we are to achieve the green transition, the need for alternative protein sources will be enormous, and we believe bacteria can become a very popular alternative, Benjamin Anderschou Holbech Jensen concludes.

You can read more about Benjamin and his group on their website, X or LinkedIn.

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