Poop has its uses too. Faecal transplants are the new treatment for cancer, liver disease – ThePrint

Bengaluru:About three and a half years ago, Joseph,suffering from severe alcohol-associated hepatitis (SAH) as well as lung tuberculosis, was lying in a semi-coma at Rajagiri Hospital in Aluva, Kerala. The 65-year-olds liver was deteriorating rapidly.

Over the course of his hospitalisation, he attended his daughters engagement ceremony chaperoned by medical attendants. However, he worried that he would not live to see her wedding.

He couldnt get the recommended treatment of steroids for his liver due to his TB. He was told that a liver transplant was the only procedure that could save him, but since he was also suffering from SAH, to prevent the risk of a relapse, he needed to go through a mandated sobriety period of six months before surgery.

But Joseph did not have the luxury of time. That is when he was offered an unusual option Faecal Microbiota Transplantation, or stool transplant.

It is what it sounds like. Faecal Microbiota Transplantation (FMT), also called bacteriotherapy, is a procedure where human stool with good bacteria from a healthy, screened donor is transplanted into the intestine of the recipient patient through the mouth, nose, or via an enema.

The procedure restores the gut bacteria the beneficial bacteria that line our intestines improving gut and colon health. It has been experimentally most commonly used to treat irritable bowel syndrome and other gastrointestinal disorders.

At Rajagiri,FMT has been adopted by hepatologists (liver specialists), owing to therelevance of the gut microbiome (beneficial bacteria in the intestines) in liver disease.

We thought it was strange, but they told us its a lifesaving treatment, Josephs daughter Shervia, 29, told ThePrint. Even if experimental, it was his last chance at life.

Josephs family gave their consent and the treatment began in early 2019. A faecal material suspension liquid mixed with undissolved solid matter was created from a donors stool and directly poured into a tube going into Josephs nose and to the small intestine. He was given an infusion of 100 ml for seven to eight days.

He started responding and improving almost immediately, said Shervia.

A month later, Joseph was dischargedto everyones surprise and relief, much aheadof Shervias wedding.

I had no problem. The experience was good. It is because of the treatment that I was able to attend my daughters wedding. Before the procedure, doctors had said they would not be able to allow me to attend. But today I am fine, and Im also able to drive normally, said Joseph, who has been disease-free for over three years.

Shervia said she would recommend FMT to anyone for whom liver transplant isnt an option, as it is inexpensive, easy, and efficient.

FMT procedures havebeen gaining clinical relevance since early studies in the 1950s, andthe method hasproven to be consistently and highly successful in treating gastrointestinalbacterial infections that dont respond to antibiotics.

It has been adopted in several hospitals around the world as an experimental treatment. Its usage is increasing with growing evidence that gut bacteria imbalance contributes to a host of conditions, including allergies andasthma,cancer, andliver disease.

While a handful of hospitals in India have used it, Rajagiri in Kerala is the only institute in the world to have consistently performed FMT on a case-by-case basis for severe SAH cases.

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The FMT programme at Rajagiri Hospital is headed by hepatologist Dr Cyriac Abby Philips, senior consultant and clinical scientist at The Liver Institute there.

Dr Philips, also an expert member of the Centre of Excellence in Microbiome Studies, an upcoming scientific programme beingdevelopedby the Government of Kerala,had performed hisfirst FMT in 2014 as part of his hepatology training and thesis work at the Institute of Liver and Biliary Sciences in New Delhi.

When identifying topics for his thesis, Dr Philips, speaking to ThePrint, said he came across many rigorous papers that showed intestinal microbes playing a role in the cause and progress of several liver diseases, especially alcohol-related ones.

Since FMT was already a recommended treatment for the drug-resistantClostridioides difficileinfection (CDI), Philips sought to conduct the first human pilot trial for treating SAH patients, who didnt have alternative therapies available to them, with FMT.

As part of my thesis, I started the worlds first stool transplant protocol for the sickest group of [SAH] patients in 2014, at the time equipped with our kitchen blender, donated by my wife Teena, for homogenising fresh stool in my makeshift, dingy storage room cum FMT Lab at the lowest ground level at my institute. And it paid off, he said.

We found that close to 85 per cent patients on FMT survived one year, compared to 33 per cent on non-FMT standard care in our study, he added.

Consequently, FMT has saved the lives of many liver patients at Rajagiri.

One such person is 37-year-old Deepesh. He had been suffering from liver cirrhosis in 2018, undergoing treatment in Coimbatore. He was extremely weak, had shaky legs and couldnt even eat. His urine was discoloured, indicating damage. His doctors, too, recommended Rajagiris FMT treatment.

We trusted the doctor [at Rajagiri]. Everybody knows he is an expert, he said to ThePrint.

Deepesh underwent the same transplant procedure through his nose for eight days. Since his recovery, he has felt different.

After the treatment I had no problems I had energy again and regained my appetite, he said. Deepesh continues to be in good health.

Liver disease isnt the only disorder to be cured by FMT. In fact, it is more widely adopted for gastrointestinal disorders, such as irritable bowel syndrome and more.

The very first FMT procedure conducted in India in a clinical setting on a patient was performed by Dr Avnish Seth, gastroenterologist and hepatologist currently with the Manipal Hospital in Dwarka, Delhi, in 2014.

At the time, he performed theprocedure at Fortis Memorial Research Institute in Gurugram on a patient with ulcerative colitis, caused by CDI in a patient who had undergone heart surgery as well.

The 44-year-old male patient was on ventilator support and had reduced kidney function, so the procedure was performed thrice via colonoscopy.

The patient improved rapidly without steroids and antibiotics, and Seth has continued to perform FMT procedures.

Dayanand Medical College in Ludhiana also performs FMT procedures under Dr Ajit Sood for ulcerative colitis and Crohns Disease, both forms of inflammatory bowel disease (IBD).

ThePrint reached Dr Sood and Dr Seth by email, but did not receive a response.

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The infusion of stool through a feeding tube sounds repulsive, but its far from it, assures Dr Philips.

A healthy donor is carefully selected and screened, especially for bacterial CDI, which is commonly driven by antibiotic use. Up to 100 grams of fresh stool is diluted with saline, milk, or water, and blended. This suspension is then administered through a feeding tube down the mouth or nose to the small intestine, or through a colonoscope as enema.

The stool suspension is given at the bedside and the whole process is over within 10 minutes. Since it is given deep into the small intestine, the chance of regurgitation and gaseousness from the procedure does not exist, said Dr Philips, who regularly performs the procedure for SAH and other liver diseases.

He further said that none of the patients complain of smell or distaste after the procedure because they are made to sit up for an hour post-procedure and also given medication to propel the suspension.

Dr Philips teams work has shown the benefit of FMT for a range of conditions, including alcohol addiction, antibiotic resistance, and drug-inducedliver injury.

They have also, according to Dr Philips, performed the first, largest and longest follow-up study on FMT in alcohol-associated hepatitis, and were able to show the change from bad bacterial profile to a good one starkly.

Dr Avnish Seths long-term follow-up study for ulcerative colitis had patients get periodic FMT treatments for maintenance and rescue, demonstrating successover five years.

Stool transplant was first documented in 4th century China by physician Ge Hong, and subsequently by physician Li Shizhen in the 16th century, who had their patients drinkyellow soupto treat stomach disorders. The firstpaperto be published in modern medicine for FMT in humans was in 1958.

The treatment has also been widely adopted by veterinariansand is also naturally exhibited in the wild by animals, many of whom often consume faeces of their own or other species.

The reason Joseph, Deepesh and many others have benefited from FMT is the enhanced clinical understanding of the gut microbiome, or the combined ecosystem of bacteria, fungi, and other microbes that inhabit our body, which help regulate our health and immune systems.

Also called the gut flora or microbiota, it plays a key role in digestion and healthy functioning of intestines. Disruption in the gut microbiome is believed to contribute to elevated blood sugar and cholesterol levels, fluctuations in weight, diabetes, inflammatory bowel disease, and other illnesses includingcancer.

It affects even the brain and nervous system, due to the two-way biochemical signaling mechanism called thegut-brain axis, which causes molecules produced in the intestine to affect the brain. Thus, the gut microbiome is thought to play a major role in cognition and mental health as well.

Trialsstudyingirritable bowel syndrome (IBS) have also shown that patients who had been clinically diagnosed with depression saw a remarkable improvement in their mental health after FMT.

Gut floras health is influenced by lifestyle habits and nutrition, and by diseases and antibiotics. Its disruption is exacerbated by antibiotic use and can manifest as an upset stomach of various kinds, bloating, flatulence, andevenincreased anxiety and depression.

In non-diseased people, it can be typically fixed by cutting down sugar and meat, increasing fermented and prebiotic foods, and exercising. But those with severe disease where the gut bacteria are also involved, like liver cirrhosis and SAH, undergo a more brute-force version through FMT.

When the stool transplant occurs, it regularly floods the small intestine with healthy gut flora. This likely causes the unhealthy bacteria to get displaced over the next few days and die out because the good bacteria compete for the same resources in the intestine.

It is alsolikelythat filtrates from the healthy stool, such as bacteriophages and enzymes, are the drivers of FMTs efficacy.

While FMT has been wildly successful, with the first randomised controlledtrialfor CDI treatment even stopping early due to its overwhelming positive results, it is still in the experimental stage and has extremely strict clinicalprotocols.

If performed without thorough screening, there is risk of transferring infections from donor torecipient. Adverse events in trials havedocumented mild and short-lived gastrointestinal distress that get resolved by themselves by the time the treatment is finished, but irritable bowel syndrome has been exacerbated in some.

One person in the USdiedin 2019 after receiving FMT containing a drug-resistant bacteria, whichalsoinfected one other person who received the same donors sample in pillsfrom a different batch.

The role of FMT as a therapeutic option for SAH is still in its fetal stages, warned Dr Philips. Currently, FMT must only be done within research protocols and possibly on a case-by-case basis for those interested in it after informed consent.

We need rigorous, high-quality randomised controlled trials and validation and repeatable outcomes from those trials for us to include FMT as a therapeutic option in routine clinical practice, he added.

(Edited by Zinnia Ray Chaudhuri)

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Poop has its uses too. Faecal transplants are the new treatment for cancer, liver disease - ThePrint