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Clostridioides difficile, or C. diff, is a gut bacterium that can cause severe diarrhoea and may return after antibiotic treatment. Restoring healthy gut microbes can cut that risk: the US Food and Drug Administration (FDA) approved Rebyota, a faecal microbiota product given rectally, in 2022, and Vowst, an oral capsule, in 2023, to prevent recurrence in adults.

FDA approvals of Rebyota (2022) and Vowst (2023)

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The story behind the card

C. difficile tends to take hold when antibiotics wipe out the normal mix of gut microbes, and in serious cases it causes life-threatening inflammation of the colon. For years doctors restored that mix with faecal microbiota transplants, giving stool from screened donors by colonoscopy, enema or capsule. Screening varied, and in 2019 the FDA issued a warning after two patients were infected with drug-resistant bacteria from donor stool and one died. Rebyota and Vowst are made and tested to a fixed standard. Both are approved only to prevent another episode after antibiotic treatment, not to treat an active infection.

Türkçe oku
Clostridioides difficile, bağırsakta ağır ishale yol açabilen bir bakteridir ve antibiyotik tedavisinden sonra yeniden ortaya çıkabilir. Bağırsaktaki sağlıklı mikropları geri kazandırmak bu riski azaltır: ABD Gıda ve İlaç Dairesi (FDA), yetişkinlerde enfeksiyonun tekrarlamasını önlemek için 2022'de makattan uygulanan dışkı mikrobiyotası ürünü Rebyota'yı, 2023'te de ağızdan alınan kapsül Vowst'u onayladı.

C. difficile genellikle antibiyotikler bağırsaktaki olağan mikrop dengesini bozunca çoğalır; ağır vakalarda kalın bağırsakta hayatı tehdit eden bir iltihaba yol açar. Hekimler yıllardır bu dengeyi dışkı nakliyle, yani taranmış bağışçıların dışkısını kolonoskopiyle, lavmanla ya da kapsülle vererek düzeltmeye çalışıyordu. Taramalar her yerde aynı titizlikte değildi: 2019'da bağışçı dışkısından ilaca dirençli bakteri bulaşan iki hastadan biri öldü ve FDA bir uyarı yayımladı. Rebyota ile Vowst ise sabit bir standarda göre üretilip test edilir. İkisi de yalnızca antibiyotik tedavisinden sonra yeni bir atağı önlemek için onaylıdır; süren bir enfeksiyonu tedavi etmek için değil.

Sources and further reading

Background reading: Fecal microbiota transplant
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Deliberately smiling can make people feel slightly happier. In 2022 a study of nearly 4,000 people in 19 countries found that posing a smile, or copying a smiling face, raised reported happiness a little; a subtler method, holding a pen between the teeth, gave less clear results.

The idea that the face can feed back into feelings, called the facial feedback hypothesis, goes back to Charles Darwin and William James. In a famous 1988 experiment, Fritz Strack and colleagues had people hold a pen in their teeth, which forces a smile, or between their lips, which prevents one, and those in the first group rated cartoons as funnier. In 2016, seventeen laboratories repeated that experiment exactly and found no effect. A 2019 review of 138 studies concluded that the effect is real but small and varies from study to study. The 2022 Many Smiles Collaboration, led by Nicholas Coles and designed jointly by supporters and sceptics of the idea, found that deliberate smiling could both strengthen and start feelings of happiness, while the pen method remained inconclusive.

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A 2016 estimate found that a typical adult man weighing 70 kg has about 30 trillion human cells and 38 trillion bacteria. That overturned the old claim that bacteria outnumber our own cells ten to one: the two numbers are roughly equal.

The estimate comes from Ron Sender, Shai Fuchs and Ron Milo of the Weizmann Institute of Science in Israel. Their reference man is 20 to 30 years old, 170 cm tall and weighs 70 kg. The ten-to-one figure, they found, went back to a single rough calculation from 1972 that had been repeated for decades. Almost all the bacteria live in the colon, the last part of the gut, and together they weigh only about 0.2 kg. Among human cells, red blood cells dominate the count, making up about 84 per cent, while fat and muscle cells, far fewer but much larger, make up most of the body's cell mass. The balance also shifts through the day: a single trip to the toilet empties a quarter to a third of the colon's contents.

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An adult body replaces about 330 billion cells every day, around 80 grams of cells, according to a 2021 estimate by scientists at the Weizmann Institute of Science. Close to nine in ten of those cells are blood cells.

Ron Sender and Ron Milo combined the number, mass and lifespan of every major cell type in the body. Short-lived cells dominate the count. Red blood cells live about four months, and neutrophils, the most common white blood cells, only days, so the bone marrow must make vast numbers of them every day. By mass, the largest shares come from blood cells and from the cells lining the gut, which are shed and replaced within days. At this pace, a number of cells equal to all the roughly 30 trillion human cells in the body is replaced in about three months. That does not mean the whole body is renewed: most nerve cells in the brain last a lifetime, and heart muscle cells are replaced only very slowly.

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Your gut and brain communicate through nerves, hormones, immune signals and microbes, which is why stress and digestion can affect each other.

Scientists call this link the gut–brain axis. The gut has its own network of about 500 million nerve cells, the enteric nervous system, sometimes called the “second brain”, which can run digestion largely by itself. It is connected to the brain mainly through the vagus nerve, a long nerve running from the brainstem down to the abdomen, and most of its fibres carry messages upwards, from the gut to the brain. More than 90 per cent of the body's serotonin, a chemical messenger, is found in the gut. Gut bacteria play a part too: in a 2004 Japanese study, mice raised entirely free of germs overreacted to stress. Stress can speed up or slow down the gut, one reason it often worsens irritable bowel syndrome, a common gut disorder. Most research on the microbes' role has been in animals, and human evidence is still limited.

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A placebo is a dummy treatment, such as a sugar pill. In pain studies, placebos can reduce the pain people report and also dampen activity in the brain areas that process pain, even though they contain no active drug.

The word placebo is Latin for “I shall please”. One of the first clues that the effect is physical came in 1978, when Jon Levine and colleagues studied patients recovering from wisdom tooth removal. They gave them a placebo and naloxone, a drug that blocks the effect of endorphins, the body's own painkilling chemicals. In patients who had responded to the placebo, naloxone increased the pain, which suggested that the placebo relief came from endorphins. In 2004 Tor Wager and colleagues used brain scans to show that a placebo painkiller reduced activity in pain-processing regions during a painful stimulus. Expectation works the other way too: in the nocebo effect, from the Latin for “I shall harm”, expecting harm makes symptoms worse. None of this means the pain was imaginary, or that placebos can replace effective treatment.

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