Crohn’s marker improves outcomes

Crohn’s marker improves outcomes CLINICAL | GASTROENTEROLOGY

A research group led by the Technical University of Munich (TUM) has discovered a marker at a microscopic level, which can be used to identify patients that show a high probability of suffering from an inflammation recurrence in the immediate future.

INTESTINAL STEM CELL

metabolism is facilitated by mitochondria – the in-cell power plants. Chronic inflammation processes inhibit the cells’ metabolism and lead to functional loss of these stem cells. In collaboration with the Helmholz Zentrum München and the Université de Paris, a TUM research team has discovered this connection by analysing intestinal epithelial cells of Crohn’s disease patients and comparing them to mouse model findings.

Breast Cancer

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WARNING SIGNS

A puckering of the skin of the breast. A lump in the breast or armpit. A change in the skin around the nipple or nipple discharge. Dimpling of the nipple or nipple retraction.

An unusual increase or shrinkage in the size of one breast or recent asymmetry of the breasts One breast unusually lower than the other. Nipples at different levels. An enlargement of the glands. An unusual swelling in the armpit.

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I am too young to get breast cancer

Being overweight/obese doesn’t matter

Alcohol is not linked to breast cancer

Only women with a family history of breast cancer are at risk

I have never had children, so I can’t get breast cancer Many women who are under 40 are diagnosed with breast cancer

Overweight women have a higher risk of being diagnosed with breast cancer, especially after menopause

Alcohol use increases the risk of breast cancer

All women are at risk, but family history increases the risk

Women who have never had children, or only had them after 30, have increased risk of breast cancer

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THE INTERRELATED ROLE OF STEM AND PANETH CELLS

Stem cells are indispensable for the maintenance and regeneration of tissues. Intestinal stem cells inside the intestines are intermingled with so-called Paneth cells, which are responsible for the local immune defence and for creating an environment in which the stem cells can prosper, thus termed guardians of the stem cell niche.

Patients suffering from Crohn’s disease have fewer Paneth cells and furthermore, these are limited in their functionality. The research group examined the causes for alterations in Paneth cells and attempted to determine the importance of stem cell metabolism in this context. In addition to mouse studies, the researchers analysed intestinal biopsies from Crohn’s disease patients, characterising the stem cell niche meticulously. After six months, the patients’ intestines were examined again endoscopically focusing on finding signs of inflammation.

PREDICTING CROHN’S DISEASE RECURRENCE

The study showed that microscopic alterations in stem cell niche were particularly prevalent in those patients who showed symptoms of a relapse of inflammation after six months.“These changes in the stem cell niche are a very early indicator for the start of inflammatory processes. This presents a reasonable starting point for therapeutic intervention,” explained Dirk Haller, Professor for Nutrition and Immunology at TUM.

RESTORING STEM CELL FUNCTION

In both human patients and mouse models, alterations in Paneth and stem cells coincided with decreased mitochondria functionality. Knowing that a lowered mitochondrial respiration leads to alterations in the stem cell niche, the researchers used dichloroacetate (DCA), a substance applied in cancer therapy leading to an increase in mitochondrial respiration.

The shift in cellular metabolism induced by DCA was able to restore the intestinal stem cell functionality of mice suffering from inflammation, as demonstrated in intestinal organoids, organ-like structures cultured ex vivo.

THERAPEUTIC APPROACH

“These findings point to a new therapeutic approach for prolonging the inflammationfree remission phases of Crohn’s disease,” said Eva Rath, scientist at the TUM School of Life Sciences Weihenstephan and coauthor of the study. Source: University of Munich

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