Why we should change our approach towards bacteria

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A perspective on the need for scientific research in regard to biotech startup incubation.

As a company builder and startup hub, we don’t want to just innovate business, we strive to shift the focus on social matters and build startups that generate impact.

GLOBAL THINKING, think tank of Nuremberg’s startup hub and company builder The Next Unicorn Ventures, is looking for innovative solutions on pressing social matters.

At The Next Unicorn Ventures, we believe that ideation in regard to company building and startup incubation is more than meetups, networking or workshops. We are convinced, that scientific research and development, is key for building relevant startups to transform markets, NOT to build the next copycat.

Necessity is the mother of invention. With rising numbers of non-communicable diseases like heart diseases, immunological disorders like asthma and allergies, and bowel diseases, the conservation of healthy bacteria in the human body has never been more important. Which technologies do we need to detect potential risks and prevent them? What medical potential lies in the research of good germs?

The story of bacteria — only pathogenic?

Throughout the history of microbiology most human studies had focused on disease causing pathogens and bacteria are still considered a health threat by the majority of society. The accidental discovery of penicillin by Alexander Fleming in 1928 was without a doubt one of the most powerful and successful achievements of modern science and technology. In 2019, the widespread use of antibiotics is estimated to have extended average life expectancy by two decades, shifting the focus from communicable to non-communicable diseases [1]. Nevertheless, inappropriate use and overuse of antibiotics is thought to be a major contributor to the distribution of multiple resistant bacterial strains, which may lead us into a post-antibiotic era [1].

While the discovery and development of antibiotics already started 90 years ago, the term microbiome was first suggested by Lederberg in 2001 [2]. Since then a lot of research has been done to elucidate the impact of host-microbial interaction on human health. The human body is occupied by a vast community of 10–100 trillions of microbial cells [3]. The community of microorganisms in a defined environment e. g. the human body is defined as microbiota, whereas the term microbiome refers to the entire habitat, including the microorganisms, their genomes and the surrounding environmental conditions [4].

Bacteria overwhelmingly outnumber eukaryotes, viruses and archaea by 2–3 orders of magnitude, which is why bacteria are operationally referred to as microbial cells in the human body. Those bacteria are estimated to exist with human cells in a ratio of approx. 1:1 [5]. Regarding the massive amount of microbes living on and in us, the idea has emerged that us humans form superorganisms with our microbiota in which energy and metabolites can be exchanged [6]

The Human Microbiome Project

The National Institutes of Health Human Microbiome Project (HMP), launched in 2007, was one of the first large-scale initiatives to address questions like, can changes in the normal microbiome have an important impact on health and disease [7]. The HMP focused on producing viral, eukaryotic and prokaryotic reference genomes as well as generating a baseline of microbial community structure and function from a healthy adult cohort [8]. The analysis of the collected data indicated, that the composition of microbial species differed at different body sites between individuals and at various times. In the gut, which harbors the highest density and diversity of microorganisms, e. g., the Bacteroides genus exhibited primarily inter-individual variation, while Firmicutes varied more temporally within individuals. On the other hand, microbial communities of the oral cavity and skin were less personalized and exhibited more time varying dynamics [9].

My body harbors a lot of microbes — so what?

Contemporary studies expose a compelling range of novel findings and open questions. Associations between changes in the microbiome and conditions like autism and cancer had been identified [10]. Furthermore, relations between so called dysbiosis — referring to persistent imbalance of the gut’s microbial community — and inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), diabetes, obesity, cardiovascular and central nervous system disorders had been shown [11]. Those associations of imbalanced microbiome and diseases impressively demonstrate the huge impact of the homeostasis of the community of microbes within our bodies.

Moreover, commensal microbes hold a key role in the tissue and cell development of the host. Important insights, like how the microbiome affects the host’s immune system, were provided by observing germ-free (born and raised in the absence of all microbes) animals. Germ-free mice possess e. g. defective and not fully developed intestinal immune cells, like defective gut-associated lymphoid tissue or a compromised cellular and molecular profile of the intestinal immune system [12]. Widespread antibiotic use altered diets and other societal factors may induce shifts in the microbiota composition leading to dysbiosis. Since the microbiota affects the development of the adaptive immune system, it is hypothesized and indicated by mouse studies that dysbiosis may affect autoimmunity by altering the balance of tolerant and inflammatory members of the microbiota [12].

How we can make the “right” microbes want to call us their new home

Interestingly, research revealed that the transfer of gut microbiota from mice with dextran-sodium sulfate induced colitis, which showed alteration in its composition compared to healthy subjects, could induce acute colon inflammation in mice that benefit from a protective genotype on colitis [13]. Findings like this demonstrate in a fascinating manner how microbes influence our health. Therefore, it is vitally important to consider the microbiome in our everyday healthcare. The human gut microbiome is affected by various conditions like sex, body mass index and fiber intake [14].

Defining a healthy microbiome had been a major challenge in the microbiome research. In general, high microbiome diversity and temporal stability has been associated with health. A relative lack of diversity on the other hand is apparent in the gut microbiome in diseases like IBD, obesity and diabetes. It has been hypothesized, that consistently reduced gut microbial diversities may be responsible for higher chronic disease rates in developed countries. Humanized mice develop depletion on microbial diversity on a refined sugar and low-fiber diet, indicating the western diet to play a crucial role in the loss of diversity [15]. Besides the unhealthy refined sugar and low-fiber diet, other factors like antibiotic use and cesarean section can disturb microbial development affecting immunological disorders like asthma and allergies [16]. Contrary to that, probiotics (live microorganisms improving gut flora) were shown to possess health benefits like preventing coronary heart diseases by reducing serum cholesterol, controlling blood pressure or improving allergy symptoms to name a few [17]

Together, all those findings demonstrate the importance of microbiota in our bodies. Microbes especially bacteria should no longer be belittled to dangerous pathogens but recognized as important contributors to our health. The microbiome research is still in its beginning. Progress in this field may lead to new possibilities for therapies and healthcare.

Thus, we deal with innovation management, trend scouting, as well as scientific research at The Next Unicorn Ventures in collaboration with our think tank GLOBAL THINKING.

We are looking for founders and startups as well as professional and semi-professional investors in the field of healthtech, life science / biotech or food / nutrition.

Written by Andrea Bayer, Scientific Research Analyst
at
The Next Unicorn Ventures | GLOBAL THINKING

Sources:

1. Denny, K.J., et al., When not to start antibiotics: avoiding antibiotic overuse in the intensive care unit. Clinical Microbiology and Infection, 2019.

2. Lederberg, J. and A.T. McCray, Ome SweetOmics — A genealogical treasury of words. The Scientist, 2001. 15(7): p. 8–8.

3. Ursell, L.K., et al., Defining the human microbiome. Nutrition reviews, 2012. 70 Suppl 1(Suppl 1): p. S38-S44.

4. Marchesi, J.R. and J. Ravel, The vocabulary of microbiome research: a proposal. Microbiome, 2015. 3(1): p. 31.

5. Sender, R., S. Fuchs, and R. Milo, Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol, 2016. 14(8): p. e1002533.

6. Cerf-Bensussan, N. and V. Gaboriau-Routhiau, The immune system and the gut microbiota: friends or foes? Nature Reviews Immunology, 2010. 10(10): p. 735–744.

7. Peterson, J., et al., The NIH human microbiome project. Genome research, 2009. 19(12): p. 2317–2323.

8. Methé, B.A., et al., A framework for human microbiome research. Nature, 2012. 486(7402): p. 215–221.

9. Lloyd-Price, J., et al., Strains, functions and dynamics in the expanded Human Microbiome Project. Nature, 2017. 550: p. 61.

10. Proctor, L.M., et al., The Integrative Human Microbiome Project. Nature, 2019. 569(7758): p. 641–648.

11. Belizário, J.E. and J. Faintuch, Microbiome and Gut Dysbiosis, in Metabolic Interaction in Infection, R. Silvestre and E. Torrado, Editors. 2018, Springer International Publishing: Cham. p. 459–476.

12. Lee, Y.K. and S.K. Mazmanian, Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System? Science, 2010. 330(6012): p. 1768–1773.

13. Nunberg, M., et al., Interleukin 1α-Deficient Mice Have an Altered Gut Microbiota Leading to Protection from Dextran Sodium Sulfate-Induced Colitis. mSystems, 2018. 3(3): p. e00213–17.

14. Dominianni, C., et al., Sex, body mass index, and dietary fiber intake influence the human gut microbiome. PloS one, 2015. 10(4): p. e0124599-e0124599.

15. Lloyd-Price, J., G. Abu-Ali, and C. Huttenhower, The healthy human microbiome. Genome medicine, 2016. 8(1): p. 51–51.

16. Bokulich, N.A., et al., Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med, 2016. 8(343): p. 343ra82.

17. Kechagia, M., et al., Health Benefits of Probiotics: A Review. ISRN Nutrition, 2013. 2013: p. 7.

GLOBAL THINKING

The Next Unicorn Ventures

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The Next Unicorn Ventures is the new Startup Hub and Company Builder of valvisio group, based in the heart of Nuremberg with a second branch in Berlin.

GLOBAL THINKING

Think Tank & Innovation Lab

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