Recent studies have considerably expanded
the collective knowledge of the human microbiome. Research has
clarified the relations between the structure and functional
capacity of the bacterial microbiome and a variety of health
conditions. The further exploration of such interactions
promises to lead to new methods for diagnosing and treating
diseases. R&D tax credits are available to support
companies engaged in better understanding the role of the
microbiome in human health and disease.
The Research &
Development Tax Credit
Enacted in 1981, the federal Research and
Development (R&D) Tax Credit allows a credit of up to 13%
of eligible spending for new and improved products and
processes. Qualified research must meet the following four
criteria:
New or improved products,
processes, or software
Technological in nature
Elimination of Uncertainty
Process of Elimination
Eligible costs include employee wages, cost of supplies, cost
of testing, contract research expenses, and costs associated
with developing a patent. On December 18, 2014 President
Obama signed the bill extending the R&D Tax Credit for the
2014 tax year.
The Human Microbiome
A regular human being shares its life with
trillions of microbes. In fact, while the body is made of
around ten trillion cells, it harbors a hundred trillion
bacteria.
The immense community of microbes residing in and on the human
body is collectively known as the microbiome, or
microbiota. Besides bacteria, it includes archaea,
viruses, and eukaryotic organisms that together can weigh
between 1 and 3 pounds.
Distributed among different parts of the body, the human
microbiome is highly complex, varied, ever changing, and
context-dependent. Consequently, there is little consensus as
to the existence of a “healthy” or “normal” microbiome. In
other words, everyone’s microbiome is unique and constantly
changing.
In spite of this variability both in terms of compositions and
concentrations, the value of the human microbiota in relation
to its host physiology is unchangeable.
The microbes in our bodies perform crucial tasks, such as 1)
contributing to metabolic functions; 2) protecting against
pathogens; and 3) educating the immune system.
Gut bacteria are an interesting example of the symbiotic,
mutually beneficial relationship between host and microbiome.
They are integral to the digestion process due to their
capacity of generating nutrients from materials that would be
otherwise indigestible.
The microbial community in one’s body is also key for the
education of the immune system, which must learn to tolerate
it while appropriately responding to pathogens.
Recent Findings
Research has revealed that changes in our
microbiome accompany various health conditions. Recent studies
are transforming the perceived role of the microbiota in human
health and disease.
For instance, the idea that bacteria are primarily a cause of
disease has been largely challenged. It is now understood that
“good” and “bad” microbes coexist in healthy individuals, and
that imbalances between these two groups can trigger disease.
The following table summarizes some of the recent findings.
Irritable
Bowel Syndrome (IBS)
Recent
findings have reinforced the role of the microbiome in
IBS. Therapies targeted at the microbial stimulus,
including dietary changes, probiotics, and antibiotics,
have shown encouraging results.
Clostridium
Difficile Infection (CDI)
CDI
is a prime example of a human disease that develops as a
result of critical changes to the gut microbiome and CDI
is effectively treated by microbiome-based therapy. The
use of fecal microbiota transplant, a kind of
restoration therapy, in the prevention of recurrent CDI
has an efficacy of about 90 percent.
Inflammatory
Bowel Disease (IBD)
Even
though IBD is explained by genetic predisposition, not
everyone with the genes manifest the disease. Research
shows that bacteria in the microbiome could be
responsible for triggering this condition. People with
IBD tend to have dysbiosis, with less of the friendly
bacteria and more types of bacteria that cause gut
inflammation. However, it remains unclear whether
microbial changes contribute to disease pathogenesis or
develop as a result of local inflammation.
Cardiovascular
Disease
A
recent study pointed to the fact that gut bacteria are
responsible for turning lecithin - a nutrient found in
egg yolks, liver, beef, pork, and wheat germ - into an
artery-clogging compound called TMAO. Blood levels of
TMAO can successfully predict heart attack, stroke, and
death, independently of other risk factors. This
discovery can lead to a new preventive approach to
cardiovascular disease, which would involve altering gut
bacteria.
Autoimmune
Diseases
In
autoimmune diseases, such as multiple sclerosis, lupus,
and rheumatoid arthritis, the immune system attacks the
body's own tissues. The microbiome is crucial in
training the immune system during childhood. Studies
have suggested that certain types of microbes living in
the gut may protect us from autoimmune diseases, while
others seem to make us more vulnerable.
Diabetes
Studies
have shown that people with type 2 diabetes have
distinct microbiome compositions differing from healthy
individuals. Gut bacteria can modify the metabolism,
changing how and what nutrients the body absorbs.
Experimental microbiome-based therapies have somewhat
successfully improved insulin responsiveness.
Obesity
Studies
have linked obesity and the microbiome in different
ways. Gut bacteria can contribute to metabolic disorders
that favor weight gain. Concurrently, a diet high in
fat, sugar, and simple carbs negatively affects
"healthy" gut microbes that keep us thin while it
encourages the development of "unhealthy" microbes that
make us obese. Interestingly enough, when obese people
lose weight, their microbiota changes accordingly.
Asthma
According
to recent studies, bacteria in the lungs might play a
role in the susceptibility to asthma. Lungs of
asthmatic adults are reported to have far more bacteria
than the lungs of people without asthma. Additionally,
individuals with more severe cases of asthma had a
greater diversity of bacteria than patients with less
acute disease.
Cancer
Recent
studies have established direct connections between
certain microbes and cancer. Examples include H. pylori
bacteria, a common cause of stomach ulcers, which is
also associated with cancers of the stomach and
esophagus; Hepatitis B and C, which greatly increase the
risk of liver cancer; the sexually transmitted human
papilloma virus, which is associated with many cervical
cancers; and the Epstein-Barr virus, the cause of
mononucleosis, which is associated with lymphomas and
other cancers.
Autism
Studies
have shown that autistic children have different
microbes living in their intestines than children
without the disorder. Even though the relation between
gut bacteria and autism remains unclear, researchers
have suggested that they may actually contribute to the
disorder. One hypothesis is that a leaky gut, a common
condition in autistic patients caused by microbial
imbalances, may allow harmful substances to pass into
the bloodstream, eventually reaching the brain.
Experimental probiotic therapy by the California
Institute of Technology was reported to alleviate
autism-like behaviors in mice.
Challenges and Ongoing
Research
The study of the human microbiome is one of
the most promising areas of medical research, and one that
could lead to a revolution in human health. A better
understanding of the tremendous complexities surrounding the
microbiota could unlock major therapeutic breakthroughs.
Recent studies have pointed to connections between the
microbiome and a wide range of conditions. In most cases, the
outstanding challenge is to understand whether these
connections are mere correlations or if they indicate
causation. Once causality is demonstrated, microbes could be
used to predict or modify disease states.
With the objective of clarifying such connections, a group of
37 scientists from various universities and research
institutions have created the American Gut Project, the
world's largest open-source science project to understand the
microbial diversity of the human body.
This massive citizen experiment has already analyzed the
microbiomes of over nine thousand people. By gathering an
unprecedented amount of data on the microbes that inhabit the
human body, the project hopes to understand the complexities
of the microbiota and to elucidate its relation to factors
such as racial and ethnic background, medication, and
lifestyle choices, such as diet and exercise.
Also with the objective of unveiling microbiome patterns and
their relation to health and disease, the National Institutes
of Health has created the Human Microbiome Project. In 2013,
it awarded three grants for promising university initiatives
that shed light on the limitless potential of microbiome
research:
A joint project between Stanford
University and Washington University in St. Louis will
examine the microbes in the gut and nose and determine how
alterations in certain microorganisms (for example during
viral infections) may trigger the development of diseases
such as diabetes.
A second joint project between the
Broad Institute and Harvard School of Public Health, will
assess the populations and physiological activities of gut
microbes in people with Crohn’s disease and ulcerative
colitis.
A third project, conducted by a
research team at Virginia Commonwealth University in
Richmond, will study bacteria that live in the vagina and
assess the roles these bacteria play in health and disease
in pregnant women as well as in their babies, particularly
for preterm birth.
The three projects will use several ‘omics’ approaches,
including genomics, transcriptomics, and proteomics to follow
the dynamic changes in the microbiome and in the host. In
addition to such groundbreaking scientific methods, big data
analytics should also be an integral tool in microbiome
research.
The Birth of a Market
The potential of microbiome research is
limitless. Thanks to cheaper and more efficient
gene-sequencing machines along with the ability to manipulate
vast amounts of genetic data, so is the potential for
microbiome-based medical innovation.
Throughout the country, biotechnology companies are working to
transform our expanding knowledge of the microbiome into
marketable solutions, such as new drugs and therapies.
Perspectives are extremely positive. Demand for
over-the-counter probiotics products has grown steadily,
demonstrating an unprecedented awareness about the role of
bacteria in health. The probiotics industry, which includes
yogurts, foods, beverages, and supplements, generates nearly
$30 billion annually.
San Francisco-based Second Genome is determined to become a
new kind of drug company; one that uses microbiome knowledge
to create therapies that strengthen or emulate bacteria,
generating a clear and decisive beneficial impact on users.
Their primary objective is to create a drug for inflammatory
bowel disease (IBD). Their second, more ambitious order of
business is to develop a microbiome-based therapy for
metabolic diseases such as type 2 diabetes.
The four-years-old company focuses on bioactives, secretions
of proteins, and metabolites produced by gut bacteria that
affect our bodies just as drugs do. Their idea is to identify,
patent, and produce bioactives that mimic the secretions of
healthful gut bacteria and develop substances that block the
effects of harmful ones.
According to Second Genome researchers, an important
innovation in microbiome drugs is that they would stay in the
gut rather then entering the users’ circulatory system, what
would considerably limit side effects.
With ongoing partnerships with Pfizer and Janssen, the
pharmaceutical arm of Johnson & Johnson, and its research
collaboration with the Mayo Clinic, Second Genome expects to
get a drug for IBD into trials within 18 months.
Boston-based Vedanta is also partnering with Johnson &
Johnson to develop a “bioactive” drug and synthesized bacteria
that should have a positive effect on the lining of the gut.
The company recently announced a license agreement with
Janssen for its lead IBD microbiome pharmaceutical candidate,
which has demonstrated efficacy in published preclinical
studies using models of autoimmune disease.
Another approach to microbiome pharmaceuticals consists of
packaging live strains of bacteria to be used as therapy – the
idea of “bugs as drugs”. Based in New York, Assembly
Biosciences is working in the identification of bacterial
strains that could cure C. difficile sufferers. Their
objective is to synthesize such strains, package them in
capsules, and deliver them directly to the colon of patients.
Biotech companies also envision creating microbiome-based
metadrugs. Alterations in the microbiota could enhance the
efficacy or reduce the side effects of other drug treatments,
including chemotherapy. An interesting example comes from
Broomfield, Colorado, where Microbiome Therapeutics is
developing a prebiotic that, by altering gut flora, could help
type 2 diabetes patients better respond to the diabetes drug
Metformin.
Microbiome-Related
Opportunities
As the role of the microbiome in health and
disease becomes clearer, microbiomial testing should become a
major global business. Routine physical exams should soon
include a gut bacteria analysis. Aiming to explore this
market, California-based Ubiome, a crowdfunded, $6
million-plus startup, provides analysis for anywhere between
$89 and $399.
Microbiome research should also create exciting opportunities
in the food and beverages market. The Nestlé Institute
of Health Sciences, which aims to develop new products that
bridge the fields of nutrition and health care, recently
invested $65 million in Seres Health, a Cambridge,
Massachusetts-based biotech startup specializing in microbiome
therapies.
Animal microbiome research is also a promising market. The
livestock industry is increasingly interested in probiotic
supplements for cattle and chicken, which can be a more
natural alternative to antibiotics when trying to influence
animals’ health and weight.
Conclusion
The microbiome represents one of the great
frontiers of human health. Intensive research increasingly
suggests that many of the answers we so desperately seek might
be inside of us. The development of microbiome drugs and
therapies as well as the application of microbiome knowledge
into nutritional and animal products represent a major
opportunity for innovation.
