A capsule packed with electronics and genetically engineered living cells displayed by researchers at MIT. A smaller version of the capsule could eventually be used in humans to find signs of ulcers and inflammatory bowel disease. Image for representational purpose only.
| Photo Credit: AP

The rising incidence of Inflammatory Bowel Disease (IBD) across the globe has become a concern for doctors. While early diagnosis is lacking, diagnosis in itself is challenging considering that other conditions could mimic IBD.

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“IBD is a significant problem. It comprises Ulcerative Colitis and Crohn’s Disease and is characterised by inflammation. It is different from Irritable Bowel Syndrome which is predominantly non-inflammatory,” said Jonathan Leighton, president at the American College of Gastroenterology, U.S.

“Both Ulcerative Colitis and Crohn’s Disease are complex immune-mediated diseases; there is a dysregulated immune response. We do believe there are genetic markers that contribute to the disease but not in isolation. There is a synergy between the external environment and gut bacteria,” he added.

There is an increasing incidence of IBD across the globe. including in North America and western Europe. “The prevalence is also rising… From 0.5% right now, the prevalence will increase to 0.6% in America,” he said.

Early onset

There is also a rise in early onset cases among those under 18. For the Indian perspective, Vineet Ahuja, Professor of Gastroenterology, All India Institute of Medical Sciences, New Delhi, has pinpointed a challenge in diagnosing Crohn’s disease. “We have peculiar issues such as intestinal tuberculosis, which is common in India and resembles Crohn’s disease. The phenotype is very similar, and so is the clinical presentation. As a result, the challenge is greater,” he said.

On incidence in India, Dr. Ahuja observed that lifestyle changes have contributed. “What was an uncommon condition three decades ago has become much more common. Changes in lifestyle, a Westernised diet with high fat and high sugar, processed and packaged food cause an insult to the gut epithelium, precipitating inflammation.”

T. S. Chandrasekar, founder and chief gastroenterologist, MedIndia Hospitals and Academy, and the Governor of American College of Gastroenterology, India region, said the incidence of IBD has almost doubled in India from 1990 to 2019, with a rise in the death rate as well.

A study in Tamil Nadu showed that there were more cases of Crohn’s Disease than Ulcerative Colitis. Nearly 50% of IBD were Crohn’s Disease and 40% were Ulcerative Colitis. It is important to catch patients early so treatment is better, he said.

Dr. Leighton noted that in terms of diagnosis there is still a delay in diagnosis, particularly among the young. “The symptoms of IBD overlap with Irritable Bowel Syndrome. This does delay diagnosis. Individuals with alarming symptoms such as bleeding and severe abdominal pain need a complete evaluation,” he said.

Also Read | Urbanisation spurs rise of Inflammatory Bowel Disease in rural Telangana

Delay in diagnosis

There are other diseases that mimic IBD, and there is a need to rule out infections as well. “There is no single diagnostic test for Ulcerative Colitis or Crohn’s Disease. It is a combination of a physical, laboratory, and endoscopy tests. We have come a long way in the treatment of IBD. Over the last 25 years, biological therapy has emerged that uses monoclonal antibodies specifically directed at inflammatory pathways. Several biologics have been developed to target different parts of the inflammatory pathways to control the disease thereby decreasing hospital stays and surgeries. In addition, we have developed small molecules that can be given orally that have had a significant impact.”

Both stressed that the cost was a challenge. “There is no cure. It is a lifelong disease. So, in India, we are looking at low cost therapy such as faecal microbiota transplantation along with regular medication,” Dr. Ahuja added.

Environmental factors play a big role in IBD, Dr. Leighton said, adding: “This includes smoking and antibiotics. There are no human studies that have proved the role of diet, but we do think some foods such as super processed foods have the potential to be pro-inflammatory. A healthy diet avoiding highly processed food, and consuming wholesome food — for instance a Mediterranean diet — is recommended.”

Dr. Ahuja said patients are advised to avoid being restrictive about their diet as they could become malnourished. “Packaged and processed foods should be avoided. We have an anti-inflammatory diet containing curd and buttermilk, and less milk, more rice and millets, fresh fruits, and vegetables. Avoid red meat and consume fish. This seems to be helpful,” he said.

“You are more microbes than human.”

It is possible you have had this factoid thrown at you, with the thrower claiming that the microbes in our bodies outnumber our own cells 10 to one.

But according to an assessment published in Nature Microbiology, this is a myth. In a 2016 study the assessment’s authors cited, researchers from Israel and Canada estimated a 70 kg “reference man” to have 38 trillion bacterial cells and 30 trillion human cells. Most current estimates of the size of the gut microbiome are also based on adults living in the urban areas of high-income countries, they added.

The authors, Alan Walker, senior research fellow at the Rowett Institute, University of Aberdeen, and Lesly Hoyles, professor of microbiome and systems biology, Nottingham Trent University, poked holes into this and 11 other popular claims that assail the human microbiome – the community of microbes living in the human body.

In the last two decades, microbiome research has gone from a “niche subject area” to “one of the hottest topics in all of science,” Dr. Hoyles said. The flip side of this is “hype and a temptation to over-simplify the really complex microbial interactions and activities occurring in our guts”.

Varun Aggarwala, assistant professor of biomedical and life sciences at Jio Institute, Navi Mumbai, who studies microbiome therapeutics, described the assessment as a “timely intervention that can bring nuance to the field of microbiomes.”

Here are the 11 other claims the article checked:

1. The age of the field

One of the more benign misconceptions the assessment takes aim at is that microbiome research is a new field. But according to the authors, scientists had described bacteria inhabiting the gut, such as Escerichia coli and Bifidobacteria, and speculated on their benefits in the late 19th and early 20th centuries itself.

2. Who named the field?

Many have credited Joshua Lederberg, a medicine Nobel laureate, with naming the field in 2001. But researchers had used the term in its modern form more than a decade earlier. According to a June 2017 paper that the authors cite, Whipps J.M., Lewis K., and Cooke R.C. used the term in 1988 to describe a community of microbes in a book.

3. The real number of microbes

Some of the more prevalent and more harmful myths concern the size of the microbiome. The absolute microbial cell numbers in one gram of human faeces have been exaggerated 10- to 100-fold. The actual number is around 10¹⁰-10¹², according to the authors.

4. The mass of the microbiome

Many research articles have stated that the human microbiota weigh 1-2 kg, but it only weighs about half a kg or less, the authors wrote. The 2016 study by Israeli and Canadian researchers estimated that it weighed about 200 grams.

5. From mother to child

Contrary to some opinions, mothers don’t pass their microbiomes to their children at birth. Some microorganisms are directly transferred during birth but they constitute a small fraction of the human microbiota. A smaller fraction of these microbes also survives and persists through the child’s life. “Every adult ends up with a unique microbiota configuration, even identical twins that are raised in the same household,” the authors noted.

6. Good or bad?

Some researchers have suggested (see here, here, and here, e.g.) that diseases are caused by undesirable interactions between microbial communities and our cells. But the authors wrote that whether a microbe and its metabolite are ‘good’ or ‘bad’ depends on the context. For example, most humans carry a species of bacteria called Clostridium difficile without any diseases for life. It causes problems only in the elderly or in people with compromised immune systems.

They acknowledged that diseases have been correlated with changes in the composition of the microbiome and that such changes could exacerbate some diseases (like inflammatory bowel disease). But they added that it is “extremely difficult” to implicate a specific profile of microbes, or changes to them, in a disease.

7. The firmicutes-bacteroidetes ratio

One myth correlates obesity with the ratio of two phyla of bacteria, firmicutes and bacteroidetes. The problem: the level of phyla is too broad to comment on effects with confidence. A phylum is a group within a kingdom. In the descending order of classifying organisms, a kingdom comprises different phyla; a phylum comprises classes; then there are orders, families, genuses, and, finally, species. Even within a bacterial species, several strains behave differently, causing the host to manifest different clinical symptoms. 

8. Not redundant

Some researchers have swung the other way, claiming that different microbes are actually functionally redundant. But the authors wrote that while different bacteria in the human microbiome perform some common important functions, many functions are the preserve of a few species.

9. Sequencing is not necessarily unbiased

The authors noted that the notion that “sequencing is unbiased” is a misconception – that biases can be introduced at various stages of studies based on the microbes’ genetic material, from collecting samples to storing them, even in the choice of software to analyse sequence data.

10. The standards question

According to the authors, there is a common opinion in microbiome research that researchers need standardised methods so that they can compare the findings of different studies. But the assessment stressed that no methodology is perfect and that adopting one universal methodology would come at the cost of turning a blind eye to the limitations of the chosen method.

11. The culturable microbiome

Is it difficult to grow microbes from the human microbiome in the lab? Yes, many say, but the authors pointed to work in the 1970s when scientists cultured diverse microbiome species from the gut. “So current gaps in culture collections are at least in part attributable to a lack of previous effort rather than an inherent ‘unculturability’,” they noted.

Joel P. Joseph is a freelance science journalist and researcher.