THE IMPORTANCE OF
A HEALTHY MICROBIOME*
The human microbiome, ‘the flora and fauna of our bodies’, has been at the centre of scientific investigations for hundreds of years, but clinical research has significantly increased in the last decade and accelerated further in recent years. Today, we have major (virtual) conferences with full focus on this sector, and the number of ongoing clinical trials in this area is now close to 2000. Despite the pandemic, 2020 saw an unprecedented number of new microbiome-related patents granted, exceeding 600.
With this recent uptake in scientific research, the amount of evidence showing that the human microbiome plays a crucial role in our health, has grown exponentially. Historically, gut and gastrointestinal disorders have been focal points, but emphasis has lately been widened to other indications, such as obesity, immunology, skin health, as well as infectious diseases - currently there are about 40 trials exploring the link between COVID-19 and the microbiome.
As we now understand, frequently cited co-morbidities for COVID-19, such as obesity or diabetes, exacerbate the course of the disease. These underlying conditions have also been linked to gut microbiome dysbiosis. This latter has a specific negative impact since the gut microbiome plays a key role in priming mucosal defence and wider immunity.
Since the beginning of the pandemic, tracking gut imbalances has proven to be a relatively accurate predictor for COVID-19 severity and mortality. It has been reported (1) that prediction algorithms have an accuracy of 92% and 85% for stool and oral microbiome, respectively. Furthermore, stool microbiome, combined with clinically relevant variables such as clinical symptoms and co-morbidities, could further improve accuracy of prediction to 96%.
Findings have shown that the specific presence of Entrococcus faecalis, an intestinal bacterium recognised as a pathobiont, was the top microbe associated with disease severity, while the oral microbe Porphyromonas endodontalis was discriminatory for severe disease manifestation.
These findings are important in two aspects - for treatment and for protection.
Sequencing of the microbiota of patients with COVID-19 infection (2) showed a significant decrease in Bifidobacteriaceae and Lactobacillaceae, the main families of symbiotic bacteria, as well as an increase in opportunistic bacteria such as Corynebacteria or Ruthenibacteria. Gut microbiome changes resulting from COVID-19 infection have been suggested by other reports as well, with correlated serum levels of IL-18 with the presence of Streptococcus species and lower relative levels of Bacteroidetes, Roseburia, Faecalibacterium, Coprococcus, and Parabacteroides (3). An increase in other opportunistic pathogens, such as Coprobacillus, has also been seen. These can upregulate ACE-2 receptor expression (4), while the specific regulation of ACE-2 receptor expression by bacteria has been noted to be highly likely to impact viral load and severity of infection (5).
On the other hand, and consistent with Tao et. al. (6), the presence of specific immune modulating bacteria such as Facecalibacterium prausnitzii, Eubacterium rectale and Bifidobacteria has been correlated with reduction in inflammatory immune markers such as CRP and inflammatory cytokines, implying these bacteria can restore immune homeostasis (7).
Trial data indicates that microbiome profiling could be important in pinpointing those patients that could be potentially significantly impacted by the infection, both in the short and long term.
This also means that for treatment, in addition to managing viral infection during COVID-19, targeting microbiome imbalances as supplementary approach could positively impact disease course, and eventually support the restoration of full health.
A further consideration is how to utilise the microbiome to address the expected long-lasting effects of COVID-19 on the gut, which could mean potential further negative consequences on immune, metabolic and neurological functions.
This three-pronged impact of the microbiome in the profiling and infection management in the short and long term could be a significant part of the ongoing COVID-19 research.
THE MICROBIOME’S ROLE IN TREATMENT OF COVID-19
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As studies suggest, the microbiome is also critical for our health and wellness, and plays a role in improving immunity prior to an infection. A thorough understanding of the connection between immune health, the microbiome and how it is affected by diet, could provide relevant information for potential prophylactic measures.
The impact of dietary factors on the gut microbiome is well recognised and during the pandemic (8) certain dietary practices have been promoted in order to boost immune function. For instance, inclusion of fibres, prebiotics and probiotics may contribute to enhancing immune health, via direct effects on the composition and function of the gut microbiome. Today, there are numerous microbiome-based therapeutics being evaluated for their potential to protect against future outbreaks.
In addition, it is important to emphasise that a healthy microbiome is one with plenty of microbiomes living in harmony with our bodies.
During the pandemic, guidelines implemented to control the transmission of the virus included travel barriers, closure of shops and restaurants, quarantine, social distancing and increased sanitation. All these measures have contributed to reducing viral burden overall but due to significant less exposure to microbes, they are likely to alter the human microbiome. The heightened use of sanitisers and antibiotics will likely bring further effects. Today, we cannot yet see the real consequences of these restrictions on microbiome composition and function (9, 10) but we do know that on the long term we can expect significant changes. This will be especially true for neonates and infants, as the microbiome plays a key role in priming healthy development in the first three years of life.
The emergence of such a germ-fearing culture is a real concern and it can be anticipated that increased sanitisation of our immediate surroundings will intensify in order to protect against further pathogenic threats. This will bring significant long-term effects on human health, and has the potential to drive the growing prevalence and incidence of chronic inflammatory and metabolic diseases. Therefore, we need to be mindful that microbes are key to our survival. They directly compete and actively suppress the emergence of more virulent and harmful species, and their interaction with the human physiology is beyond question.
In conclusion, re-education and reinforcement of the human health benefits of the microbiome will be a major undertaking in a post-pandemic world. However, in parallel, we have to continue advancing our scientific knowledge in order to prevent and treat infectious and chronic diseases.
A HEALTHY MICROBIOME TO IMPROVE IMMUNE HEALTH
The microbiome has entered everyday knowledge as the level of research undertaken and currently being done has risen exponentially. Its impact in the fight against COVID-19 is particularly interesting, given the revelation that it can not only be used to predict the severity of the disease, but also could be influential in how people fight off the infection in the short and longer term. This is a fascinating area of research, and we believe that we need to highlight this area of science and its long term value to the wider industry.
*Article previously published in Agro Food Industry Hi Tech 32(2) 2021.
ISABELLE DE CREMOUX
Seventure Partners | France
Isabelle de Cremoux is CEO and Managing Partner at Seventure Partners, where she established the Life Sciences division, and launched the Health for Life Capital™ funds, the first venture capital funds focused on investments ‘beyond the pill’, including the microbiome and nutrition space.