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Karolinska Institutet

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Övning i tålamod, eller hur är det att jobba som forskare?

Idag tänkte jag berätta om vårt arbete som forskare och hur det har gått för vår SweMaMi-studie hittills. Som jag skrev i höstas så studerar vår forskargrupp sambandet mellan gravida kvinnors bakterieflora (med prover från munnen, tarmen och vaginan) och olika graviditetskomplikationer. Analyserna av bakteriefloran kopplar vi ihop med enkätsvaren om kvinnans graviditet, livsstil, hälsa, matvanor, stress, tarmfunktion och annat. Dessutom ber vi föräldrarna att samla ett prov från blöjan från det nyfödda barnet och vi följer sen barnets hälsa under många år framåt. 

Idag har vi rekryterat ca 2300 gravida till studien, men färre än 2000 har skickat in prover. Vi hade hoppats på att avsluta rekryteringen nu till sommaren, men på grund av det stora bortfallet behöver vi förlänga rekryteringstiden tills vi når vårt mål av 2500 kvinnor som både har fyllt i enkäterna och skickat in proverna till oss. Sen behöver vi vänta tills alla SweMaMi-bebisar är födda för att få in de sista proverna innan vi börjar analysera. Ni förstår, det krävs väldigt mycket tålamod.

Under tiden har vi börjat analysera enkätsvaren från de första 2000 gravida som är med i studien. Det gläder oss att se att vi har nått ut till hela Sverige, ca 60% av studiedeltagarna kommer från områden utanför Stockholm. Dessutom verkar åldersfördelningen vara representativ för gravida i vårt land. När det gäller utbildning och arbete så verkar vi framför allt nå kvinnor med högskoleutbildning och heltidsjobb, vilket tyvärr inte representerar alla gravida i Sverige. Detta kommer att begränsa våra möjligheter att generalisera våra fynd till hela befolkningen. 

Hittills har ca 650 bebisar fötts av mammor som är med i studien, och för de första 444 deltagarna har vi utvärderat enkätsvaren angående matvanor och rapporteringen av depression efter förlossningen. Det verkar finnas ett samband mellan ohälsosamma matvanor och uppkomsten av depressioner, speciellt när det gäller en hög konsumtion av sötade drycker och lågt intag av grönsaker. Kanske inte helt oväntat, men ett viktigt fynd som vi ska analysera vidare med tanke på att sambandet mellan tarmfloran och vår psykiska hälsa är ett hett forskningsområde. Studier på möss visar att tarmbakterier kan påverka hjärnans utveckling och djurens beteende. Men när det gäller människor så saknas det studier som visar på samband mellan bakteriefloran och vårt mående. Framför allt är det osäkert vad som är orsak och vad som är verkan. Sambandet kan bero på flera saker, så som att det är vanligare att äta sött som tröst, men det kan även vara så att kosten påverkar måendet via bakterier. Vi vet ännu idag inte hur bakterierna i munnen, tarmen och vaginan hänger ihop i våra kroppar, därför är vår studie så viktig.

Vår forskargrupp försöker att samla in all kunskap som finns om graviditet och bakteriefloran, men kan vid dagens läge inte lämna några rekommendationer om specifika pre- eller probiotika som skulle kunna förebygga missfall, för tidiga förlossningar eller depression hos blivande mammor. Ibland kan det kännas lite frustrerande, men ju mer förståelse vi får för komplexiteten i samverkan mellan våra kroppar och de trillioner av mikrober som lever i och på oss, desto svårare blir det att göra tvärsäkra uttal om vilka som vi bör tillföra. Tyvärr sprids det många ovetenskapliga råd av självutnämnda experter i media. Vetenskapen kan idag bara rekommendera medelhavskost och en livsstil med mycket fysisk aktivitet för att undvika att bakteriefloran påverkar graviditeten och fosterutvecklingen på ett negativt sätt. 

Så mer tålamod krävs, men om alla gravida innan vecka 19 som läser detta kan tänka sig att delta i SweMaMi studien så kommer vi tillsammans en bit framåt. Hjälp oss att sprida informationen om studien och att basera de rekommendationer som ges till gravida på vetenskapliga fakta.

Anmäl dig till att vara med i vår studie på www.swemami.se. Du är också välkommen att följa oss på Facebook och Instagram: SweMaMi.

Ina Schuppe Koistinen är Docent på Karolinska Institutet och jobbar på Centrum för Translationell Mikrobiomforskning med att studera bakterieflorans roll i inflammatoriska tarmsjukdomar och kvinnors hälsa. Förutom forskningen brinner hon för yoga och att guida människor till en hälsosammare livsstil. Hon är dessutom verksam som konstnär med akvarell som medium. Åsikterna i krönikan är skribentens egna.

Akvarell: Ina Schuppe Koistinen

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Karolinska Institutet

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Twins – An Important Epigenetic Tool

An important part of my work is to carefully plan my studies so that we actually measure what we intend on measuring and nothing else. Maybe this sounds straightforward but it’s not quite that easy.

As an epigeneticist, I study the impact of the environment on the genome (read more here). What makes it all difficult is that our epigenome is not static, but constantly exposed to changes from our environment. For example, if we discover an epigenetic difference between sick and healthy people, we cannot say whether the difference seen  is the cause of the disease or a consequence of it. In most cases we are studying people who are already sick. And, to make things all the more complicated, most diseases are the result of a combination of heritage and the environment.

So how do we get around around this? There are a few different ways to design a study to filter out the noise of unwanted signals, and clarify what is cause and effect. One way to sort out the noise from our genes and just study the environmental impact is to use twins. Identical twins have the same genome and to some extent a common environment, however, the older they get the more separated their living environment and habits tend to become. And this is what we benefit from when studying twins where only one twin has suffered from a particular disease.

In one of our studies, we studied epigenetic changes and rheumatic disease with the help of identical twins from the Swedish Twin Registry. And to find out more about the onset of the disease, and not just the effect, we also studied “healthy” twins who have not yet been affected by rheumatism, but who are likely to develop the disease as they have a certain type of antibody in their blood that is associated with rheumatism (antibodies against ACPA).

With this approach, we were able to identify methylation differences that were not dependent on the interference of the genes. But why do you want to do this? Well, in the vast majority of studies that investigate rheumatism, a certain group of genes pop up, the so-called HLA genes. These genes encode proteins that help our immune system talk about what is body-like or body-foreign.

The HLA genes are involved in one way or another in rheumatism, and also in many other autoimmune diseases. But, with the help of identical twins, we could identify other genes involved in addition to the HLA genes. The PCDHB14 gene was found to be differently methylated in both the “healthy” twins with ACPA antibodies in their blood and the diseased twins, suggesting that this gene is involved in the actual development of the disease.

PCDHB14 belongs to a large complex gene family that is mainly expressed in the brain and which has been reported to be involved, just like the HLA genes, in sensing what is own and body foreign. Super interesting! In the mentioned study, we could not point out which environmental risk factor or factors could possibly be behind the development of the disease, but we gained knowledge about which biological systems could be involved in rheumatism. One puzzle piece at a time!

In another study, we focused instead on one of the most common risk factors for many autoimmune diseases, namely smoking. We wanted to investigate how smoking affected MS patients and then looked at smokers, former smokers and MS patients who had never smoked. But I’ll tell you more about this in my next post here at Food Pharmacy.

Louise Sjöholm has a education in molecular biology and a doctorate in depression genetics from Karolinska Institutet. She has been working as an epigeneticist for seven years and is researching the role of the gastrointestinal tract in autoimmune diseases, i.e., diseases in which the body’s immune system attacks its own tissue. She is also interested in understanding the epigenetics of bacteria and its connection to health and disease. The views in the chronicle are the writer’s own.

Photo by Sharon McCutcheon on Unsplash

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Karolinska Institutet

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Saving the Antibiotic for Future Generations

World Health Organization (WHO) has classified the global issue of antibiotic resistance as a major threat to public health. In just Europe alone, approximately 30,000 deaths per year occur from infections with resistant bacteria and this figure is expected to have doubled in the next ten years.

In some countries, when there is risk of infection of such bacteria, the risk alone is causation enough to cancel a scheduled operation. Should we just give up then or is there light at the end of the tunnel? Well, first of all, we must change our behavior and not use antibiotics unnecessarily. Antibiotics should, in principle, be used to save lives and not for banal viral infections or colds. But if we want to save the antibiotic for future generations, new alternative treatments for infections with resistant bacteria must also be tested. These such trials are what is currently ongoing at the Center for Translational Microbiome Research, CTMR.

An alternative that seems promising is to compete the resistant bacteria in the intestinal flora with a “good microbiome” i.e., good intestinal flora. Currently ongoing in the laboratory is an experiment where resistant bacteria are supplied with a disturbed intestinal flora in test tubes and we then add “healthy intestinal flora” from a healthy donor. It is the same principle used in so-called fecal transplantation (FMT) where patients with diarrhea caused by certain antibiotics are cured with a healthy donor intestinal flora. We hope to be able to identify healthy donors whose intestinal flora can, in the future, help to compete with resistant bacteria in the intestinal flora of people who unknowingly carry. In this way, we can also reduce the risk of spreading resistant bacteria outside the body.

Another way to kill disease-causing resistant bacteria is phage therapy. Here, target-seeking viruses are used to eliminate the desired bacteria, usually with great precision. Phage therapy has long existed as a treatment option in Georgia and other post-Soviet states, but when the antibiotic entered the scene about 60 years ago the technique has not developed or advanced, as many thought antibiotics were the solution to all infectious problems. Now the researchers are beginning to realize that phage can be a good alternative when antibiotics cannot be used. Phage therapy also has the advantage that it does not interfere with the intestinal flora, which has proven to be a problem in antibiotic treatment, where even “good” bacteria are eliminated as well.

At our center, several trials are now underway. One of which we use test tubes containing good intestinal flora, then we add resistant bacteria and lastly the phages that kill them. Our results show that the phages do not disturb the intestinal flora at all and that the number of resistant bacteria decreases markedly in the test tube. The next step is to transfer this principle to humans. Today, there are occasional reports of successful treatment in patients where antibiotics did not work and where the patient’s life was rescued thanks to phages who did the job instead. A combination of phages therapy as well as supplying a dose of good intestinal flora could also be tested in some patients.

If we can prevent the spread of resistant bacteria by changing our behavior while developing new alternative treatments for infections with resistant bacteria then hope is not out. Then future generations can also use antibiotics when needed, i.e., to save lives.

Lars Engstrand is a doctor and professor at Karolinska Institute and leads the work at the Center for Translational Microbiome Research. He has been studying microorganisms in the gastrointestinal tract for over 30 years and is one of the pioneers in studying the role of the gut flora in health and disease.

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Karolinska Institutet

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A Mummy’s Diet

Two weeks ago I was on a visit to Bolzano in northern Italy. I was visiting as an expert on a scientific council to evaluate the research at the EURAC Institute for Mummy Research. In Bolzano is a museum which is home to the 5300-year-old iceman, Ötzi. Eight years ago he was thawed for just a few hours and I alongside other researchers were able to examine Ötzi.

Researchers from many different fields of research took a variety of samples from the stomach and intestines, among several other things. We have since collaborated with research colleagues in Italy, the United States, Germany and Austria to study the stomach contents of Ötzi and with new technologies, mapped residuals of proteins, fat and genetic material. We came to the conclusion that Ötzi was an omnivore who was well equipped for his hiking in the Alps for that time. He needed a lot of energy, and his diet contained a lot of fat that could be likened to today’s LCHF diet i.e., high fat and low carbohydrates. His last meal before he died consisted of red meat (mountain goat and deer), grains and some spices. He also cooked the food in a way that is similar to the smoking of meat.

In a few weeks, a state-of-the-art laboratory will be opened at EURAC to study mummies from different parts of the world. An important part is to ensure that the sample you are analyzing truly comes from the mummy itself and not from the environment. For example, in the study of intestinal flora, one must be very careful in the preparation of the sample so that no bacteria in the environment pollute the sample.

The new laboratory in Bolzano has specially designed premises to ensure this. In collaboration with us at the Center for Translational Microbiology, researchers at EURAC are working to map the intestinal flora of Ötzi with new impressive DNA technologies. The intention is to compare his intestinal flora with the intestinal flora of people today. We will also collaborate to study the stomach content and hence the diet of other well-preserved mummies from different parts of the world. There are mummies in Mexico, Peru, Switzerland, Egypt and China that are so well-preserved that the intestinal flora and perhaps dietary remnants can be mapped in the same way as Ötzi.

We hope to find out more about how people lived thousands of years ago. In addition, we can deepen our understanding of how intestinal flora looked with the diets of previous times . Who knows – we may have a Bronze Age diet on the Christmas table next year.

Lars Engstrand is a doctor and professor at the Karolinska Institute and heads the department at the Center for Translational Microbiology Research. He has studied microorganisms in the gastrointestinal tract for over 30 years and was one of the pioneers to study intestinal flora with new DNA techniques.

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