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Poop has been an easy target for microbiome research, but voyages into the small intestine shed new light on ways to improve gut health

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theconversation.com – Christopher Damman, Associate Professor of Gastroenterology, School of Medicine, of Washington – 2024-06-14 07:38:49

Much of the small intestine microbiome remains an undiscovered frontier.

Stefano Madrigali/Moment via Getty Images

Christopher Damman, University of Washington

Microbiome research to date has been much like the parable of the blind men and the elephant. How much can be said about an elephant by examining just its tail? Researchers have studied what is most readily available โ€“ stool rescued from a flush down the toilet โ€“ but have been missing the microbial masterminds upstream in the small intestine. Until recently.

Likened by some scientists to another human organ, your microbiome is collectively the tens of trillions of microorganisms that live in interconnected populations on and in your body. They serve as miniature sentinels that protect your body’s surfaces from pathogenic invaders. In the upper intestine, distinct microbial populations also aid in digestion, metabolism and even immunity.

I am a gastroenterologist who has spent the past 20 years studying the microbiome’s role in health and disease. Advances in technology are helping scientists investigate the small intestine microbiome and the promise it for better understanding and treating many diseases.

Big transformations come from small places

Certain members of the small intestine microbiome are linked to obesity and overweight, while other microbial members are linked to a healthy metabolic . Indeed, small intestine microbes aid in digestion by turning certain simple carbohydrates into the molecular building blocks of a healthy gut and body.

While analogous in function to the colon, small intestine metabolites can be quite distinct from the fiber-derived metabolites of the large intestine microbiome. Some small intestine metabolites help regulate the upper gut’s production of GIP, a sister molecule to the lower gut hormone GLP-1, which makes up the weight loss and type 2 diabetes Wegovy and Ozempic. Together, with another lower gut hormone called PYY, this triumvirate is critical for coordinating your body’s response to food by regulating your appetite and blood sugar.

Monjaro is an incrementally more powerful combination of GIP and GLP-1 compared with Wegovy and Ozempic. The full complement of these hormones is naturally stimulated by the breakdown of products from both the large and small intestine microbiome.

The upshot on gut breakdown

Research has linked a disrupted small intestine microbiome to diseases of the gut. These include irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), Crohn’s disease and Celiac disease.

These diseases are thought to arise partly from disturbances in the way the microbiome breaks down food. Celiac disease, for example, is associated with the small intestine microbiome’s decreased ability to digest gluten. IBS and SIBO are linked to the opposite: the small intestine microbiome’s ability to too readily ferment fibers and sugars.

Small intestinal bacterial overgrowth, or SIBO, shares similar symptoms with irritable bowel syndrome.

Foods like wheat, garlic, onion, beans and certain processed products that are high in FODMAPs โ€“ a set of fermentable short-chain carbohydrates โ€“ have been shown to contribute to symptoms in individuals with SIBO and IBS. Lactose-rich dairy is a high FODMAP food group implicated in lactose intolerance and linked to an overzealous small intestine microbiome.

The body’s not-so-diplomatic immunity

Diseases associated with the small intestine microbiome aren’t limited to metabolism and the gut. In the gut’s lining resides a virtual embassy of immune cells that remain in an ever-vigilant state surveying the motley stream of microbial and nutritional antigens passing through your gut.

Compromise in the security systems that separate the fecal stream from the rest of the body and the processes that keep immune responses in check are hypothesized to play a role in triggering various autoimmune conditions in which the body becomes confused as to who’s friend and who’s foe.

Studies have linked inflammatory changes in the small intestine microbiome to type 1 diabetes, where the body’s circulating immune cells attack insulin-producing cells in the pancreas, and to the extra-intestinal symptoms of Celiac disease, where immune cells can lead to destructive processes in the body’s eyes, skin and joints.

Lights shed in and on the tunnel

Up until very recently, small intestinal research has moved slowly. Scientists relied on upper endoscopy procedures, which involve sedation and inserting a small camera at the end of pinky-thick tubes through the mouth into the very first part of the small intestine.

One of the few alternatives to endoscopies has been studying patients who have had intestinal surgeries that direct portals into their small intestine via a hole in their abdominal wall.

Newly developed technologies are removing the need for sedating medications and unique anatomical situations by allowing scientists to more easily sample the furthest reaches of the gut. Such technologies include camera capsules tethered to angel-hair-thin filaments and other even more streamlined devices that create minimally invasive direct lines of access to the small intestine. Researchers have also developed capsules with sample compartments that open when they reach certain acidity levels in the body.

Poop has been an easy target for microbiome research, but voyages into the small intestine shed new light on ways to improve gut health

Improvements in endoscopy techniques are making it easier to study the small intestine.

Simon Belcher/imageBROKER via Getty Images

These new sampling techniques have unlocked unprecedented access to the upper gut, paving the way for new insights and therapies. In a real-life parallel to a childhood favorite, โ€œThe Magic School Bus, Inside the Human Body,โ€ researchers can now ride along through the gut like Ms. Frizzle and her class, shining light on the microbial secrets held within.

Accrued alliance in a still-crude science

Therapies based on early understandings of the gut microbiome have included approaches ranging from probiotics to fecal transplants and prebiotics to fermented foods.

But new treatments for gut health are still in their early days. Studying the small intestine could provide insights to improve therapeutic . A of promising future possibilities include partnering small intestine bacteria with their preferred prebiotics and personalized combinations of low FODMAP prebiotics designed to avoid small intestine fermentation.

Treatments that partner food and the microbiome are likely early harbingers of what’s to in the rapidly developing field of microbiome medicine. Researching the small intestine โ€“ and not only the gut’s tail end โ€“ might just be microbiome medicine’s most pioneering upstream start.The Conversation

Christopher Damman, Associate Professor of Gastroenterology, School of Medicine, University of Washington

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Women are at a higher risk of dying from heart disease โˆ’ in part because doctors donโ€™t take major sex and gender differences into account

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theconversation.com – Amy Huebschmann, Professor of Medicine, University of Colorado Anschutz Medical Campus – 2024-10-22 07:45:00

Rates of heart disease and cardiac events in women are often underestimated.

eternalcreative/iStock via Getty Images

Amy Huebschmann, University of Colorado Anschutz Medical Campus and Judith Regensteiner, University of Colorado Anschutz Medical Campus

A simple difference in the genetic code โ€“ two X chromosomes versus one X chromosome and one Y chromosome โ€“ can lead to major differences in heart disease. It turns out that these genetic differences influence more than just sex organs and sex assigned at birth โ€“ they fundamentally alter the way cardiovascular disease develops and presents.

While sex influences the mechanisms behind how cardiovascular disease develops, gender plays a role in how care providers recognize and manage it. Sex refers to biological characteristics such as genetics, hormones, anatomy and physiology, while gender refers to social, psychological and cultural constructs. Women are more likely to die after a first heart attack or stroke than men. Women are also more likely to have additional or different heart attack symptoms that go beyond chest pain, such as nausea, jaw pain, dizziness and . It is often difficult to fully disentangle the influences of sex on cardiovascular disease outcomes versus the influences of gender.

While women who haven’t entered menopause have a lower risk of cardiovascular disease than men, their cardiovascular risk accelerates dramatically after menopause. In addition, if a woman has Type 2 diabetes, her risk of heart attack accelerates to be equivalent to that of men, even if the woman with diabetes has not yet gone through menopause. Further data is needed to better understand differences in cardiovascular disease risk among nonbinary and transgender patients.

Despite these differences, one key thing is the same: Heart attack, stroke and other forms of cardiovascular disease are the leading cause of death for all people, regardless of sex or gender.

We are researchers who study women’s health and the way cardiovascular disease develops and presents differently in women and men. Our work has identified a crucial need to medical guidelines with more sex-specific approaches to diagnosis and treatment in order to improve health outcomes for all.

Gender differences in heart disease

The reasons behind sex and gender differences in cardiovascular disease are not completely known. Nor are the distinct biological effects of sex, such as hormonal and genetic factors, versus gender, such as social, cultural and psychological factors, clearly differentiated.

What researchers do know is that the accumulated evidence of what good heart care should look like for women compared with men has as many holes in it as Swiss cheese. Medical evidence for treating cardiovascular disease often from trials that excluded women, since women for the most part weren’t included in scientific research until the NIH Revitalization Act of 1993. For example, current guidelines to treat cardiovascular risk factors such as high blood pressure are based primarily on data from men. This is despite evidence that differences in the way that cardiovascular disease develops women to experience cardiovascular disease differently.

Clinician holding stethoscope against a patient's chest

Gender biases in health care influence the kind of tests and attention that women .

FG Trade Latin/E+ via Getty Images

In addition to sex differences, implicit gender biases among providers and gendered social norms among patients lead clinicians to underestimate the risk of cardiac events in women with men. These biases play a role in why women are more likely than men to die from cardiac events. For example, for patients with symptoms that are borderline for cardiovascular disease, clinicians tend to be more aggressive in ordering artery imaging for men than for women. One study linked this tendency to order less aggressive tests for women partly to a gender bias that men are more open than women to taking risks.

In a study of about 3,000 patients with a recent heart attack, women were less likely than men to think that their heart attack symptoms were due to a heart . Additionally, most women do not know that cardiovascular disease is the No. 1 cause of death among women. Overall, women’s misperceptions of their own risk may hold them back from getting a doctor to check out possible symptoms of a heart attack or stroke.

These issues are further exacerbated for women of color. Lack of access to health care and additional challenges drive health disparities among underrepresented racial and ethnic minority populations.

Sex difference in heart disease

Cardiovascular disease physically looks different for women and men, specifically in the plaque buildup on artery walls that contributes to illness.

Women have fewer cholesterol crystals and fewer calcium deposits in their artery plaque than men do. Physiological differences in the smallest blood vessels feeding the heart also play a role in cardiovascular outcomes.

Women are more likely than men to have cardiovascular disease that presents as multiple narrowed arteries that are not fully โ€œclogged,โ€ resulting in chest pain because blood flow can’t ratchet up enough to meet higher oxygen demands with exercise, much like a low-flow showerhead. When chest pain presents in this way, doctors call this condition ischemia and no obstructive coronary arteries. In comparison, men are more likely to have a โ€œcloggedโ€ artery in a concentrated area that can be opened up with a stent or with cardiac bypass surgery. Options for multiple narrowed arteries have lagged behind treatment options for typical โ€œcloggedโ€ arteries, which puts women at a disadvantage.

In addition, in the early stages of a heart attack, the levels of blood markers that indicate damage to the heart are lower in women than in men. This can lead to more missed diagnoses of coronary artery disease in women compared with men.

The reasons for these differences are not fully clear. Some potential factors include differences in artery plaque composition that make men’s plaque more likely to rupture or burst and women’s plaque more likely to erode. Women also have lower heart mass and smaller arteries than men even after taking body size into consideration.

Reducing sex disparities

Too often, women with symptoms of cardiovascular disease are sent away from doctor’s offices because of gender biases that โ€œwomen don’t get heart disease.โ€

Considering how symptoms of cardiovascular disease vary by sex and gender could doctors better care for all patients.

One way that the rubber is meeting the road is with regard to better approaches to diagnosing heart attacks for women and men. Specifically, when diagnosing heart attacks, using sex-specific cutoffs for blood tests that measure heart damage โ€“ called high-sensitivity troponin tests โ€“ can improve their accuracy, decreasing missed diagnoses, or false negatives, in women while also decreasing overdiagnoses, or false positives, in men.

Our research laboratory’s leaders,collaborators and other internationally recognized research colleagues โ€“ some of whom partner with our Ludeman Family Center for Women’s Health Research on the University of Colorado Anschutz Medical Campus โ€“ will continue this important work to close this gap between the sexes in health care. Research in this field is critical to shine a light on ways clinicians can better address sex-specific symptoms and to bring forward more tailored treatments.

The Biden administration’s recent executive order to advance women’s health research is paving the way for research to go beyond just understanding what causes sex differences in cardiovascular disease. Developing and testing right-sized approaches to care for each patient can help achieve better health for all.The Conversation

Amy Huebschmann, Professor of Medicine, University of Colorado Anschutz Medical Campus and Judith Regensteiner, Professor of Medicine, University of Colorado Anschutz Medical Campus

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Tracking vampire worms with machine learning โˆ’ using AI to diagnose schistosomiasis before the parasites causing it hatch in your blood

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theconversation.com – Trirupa Chakraborty, Ph.D. Candidate in Integrative Systems Biology, of Pittsburgh – 2024-10-21 07:44:00

Trirupa Chakraborty, University of Pittsburgh; Aniruddh Sarkar, Georgia Institute of Technology, and Jishnu Das, University of Pittsburgh

Blood samples of infected with a parasitic worm that causes schistosomiasis contain hidden information that marks different stages of the disease. In our recently published research, our team used machine learning to uncover that hidden information and improve early detection and diagnosis of infection.

The parasite that causes schistosomiasis completes its cycle in two โ€“ first in snails and then in mammals such as people, dogs and mice. Freshwater worm eggs enter human hosts through the skin and circulate throughout the body, damaging multiple organs, including the liver, intestine, bladder and urethra. When these larvae reach blood vessels connecting the intestines to the liver, they mature into adult worms. They then release eggs that are excreted when the infected person defecates, continuing the transmission cycle.

Since diagnosis currently relies on detecting eggs in feces, usually miss the early stages of infection. By the time eggs are detected, patients have already reached an advanced stage of the disease. Because diagnosis rates are poor, public typically mass-administer the drug praziquantel to populations in affected regions. However, praziquantel cannot clear juvenile worms in early stages of infection, nor can it prevent reinfection.

Diagram of schistosomiasis infection cycle

Schistosomiasis isn’t usually diagnosed until the late stages of the disease.

DPDx/CDC

Our study provides a clear path forward to improving early detection and diagnosis by identifying the hidden information in blood that active, early stage infection.

Your body responds to a schistosomiasis infection by mounting an immune response involving several types of immune cells, as well as antibodies specifically targeting molecules secreted by or present on the worm and eggs. Our study introduces two ways to screen for certain characteristics of antibodies that signal early infection.

The first is an assay that captures a quantitative and qualitative profile of immune response, including various classes of antibodies and characteristics that dictate how they communicate with other immune cells. This allowed us to identify specific facets of the immune response that distinguish uninfected patients from patients with early and late-stage disease.

Second, we developed a new machine learning approach that analyzes antibodies to identify latent characteristics of the immune response linked to disease stage and severity. We trained the model on immune profile data from infected and uninfected patients and tested the model on data that wasn’t used for and data from a different geographical location. We identified not only biomarkers for the disease but also the potential mechanism that underlies infection.

Why it matters

Schistosomiasis is a neglected tropical disease that affects over 200 million people worldwide, causing 280,000 deaths annually. Early diagnosis can improve treatment effectiveness and prevent severe disease.

In addition, unlike many machine learning methods that are black boxes, our approach is also interpretable. This means it can insights into why and how the disease develops beyond simply identifying markers of disease, guiding future strategies for early diagnosis and treatment.

Microscopy image of large white oval-shaped structures enclosing magenta oval-shaped structures, surrounded by smaller cells

Clusters of Schistosoma haematobium eggs surrounded by immune cells in bladder tissue.

CDC/Dr. Edwin P. Ewing Jr.

What still isn’t known

The schistosomiasis infection signatures we identified remain stable across two geographical regions across two continents. Future research could explore how well these biomarkers apply to additional populations.

Further, our work identifies a potential mechanism behind disease progression. We found that a particular immune response against a specific protein on the surface of the worm signals an intermediate stage of infection. Understanding how the immune system responds to this understudied antigen could improve diagnosis and treatment.

What’s next

Besides improving our understanding of how the immune system responds to different stages of infection, our findings identify key antigens that could pave the way for designing cost-effective and efficient approaches to diagnosis and treatments. Our next steps will include actually deploying these strategies in the field for early detection and management of disease.

The Research Brief is a short take about interesting academic work.The Conversation

Trirupa Chakraborty, Ph.D. Candidate in Integrative Systems Biology, University of Pittsburgh; Aniruddh Sarkar, Assistant Professor of Biomedical Engineering, Georgia Institute of Technology, and Jishnu DasUniversity of Pittsburgh

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More kids than ever need special education, but burnout has caused a teacher shortage

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theconversation.com – Kimber Wilkerson, Professor of Special Education, of Wisconsin-Madison – 2024-10-21 07:44:00

Many special education teachers quit after less than five years on the job.

10’000 Hours/Digital Vision via Getty Images

Kimber Wilkerson, University of Wisconsin-Madison

A growing number of students in โ€“ right now, about 15% of them โ€“ are eligible for special education services. These services include specially designed instruction for students with autism, learning or physical disabilities, or traumatic brain injuries. But going into the current school year, more than half of U.S. public schools anticipate being short-staffed in special education. Dr. Kimber Wilkerson, a professor of special education and department chair at the University of Wisconsin-Madison, explains why there’s a shortage and what needs to be done to close the gap.

Dr. Kimber Wilkerson discusses the special education teacher shortage.

has collaborated with SciLine to bring you highlights from the discussion, which have been edited for brevity and clarity.

Which students special education services?

Kimber Wilkerson: Students with a disability label receive special education services. They need these additional services and sometimes instruction in school so they can access the curriculum and thrive like their peers.

What is happening with staffing for special education?

Wilkerson: Since special education became a thing in the ’70s, there have always been challenges in filling all the special education positions.

In the past 10 years preceding the COVID-19 pandemic, those challenges started to increase. There were more open positions in special education at the beginning of each school year than in previous decades. In the 2023-24 school year, 42 states plus the District of Columbia reported teacher shortages in special education.

What is causing these shortages?

Wilkerson: One, there are fewer young people choosing teaching as a major in college and as a profession. And special education is affected by these lower rates more than other forms of education.

Also, there’s more attrition โ€“ people leaving their teaching job sooner than you might expect โ€“ not because they’re retiring, but because they are tired of the job.

They want to do something different. They want to go back to school. Sometimes it’s circumstances, but the number of people leaving the job before retirement age has increased. And in our state, Wisconsin, about 35% of all educators leave the field before they hit their fifth year.

That number is even higher for special educators. About half of special educators are out of the profession within five years.

Why do special education teachers the profession?

Wilkerson: There’s not a national study that speaks to that reason. There are some localized studies, and people report things like too much paperwork or too many administrative tasks associated with the job. Sometimes they report the students’ behavioral challenges. Sometimes it’s a feeling of isolation, or a lack of support from the school.

How are students with disabilities affected when their school does not have enough special educators?

Wilkerson: In a school that’s one special educator short, the other special educators have to take over that caseload. Instead of having 12 students on their caseload, maybe now they have 20. So, the amount of individual attention given to each student with a disability decreases.

Also, when teachers with experience leave the profession, they leave behind a less experienced group of teachers. This means the students are losing out on the benefit of those years of wisdom and experience.

What are some strategies to recruit and retain more special education teachers?

Wilkerson: There’s a range of strategies that different universities, states and school districts have taken, like residency programs.

In these programs, the person who is learning to be a teacher, and who is referred to as a teaching resident, works alongside a mentor teacher for an entire year in a school, and they get paid to do so. They’re not the teacher of record, but they’re learning and getting paid, and they’re in that school community.

Can you tell us about your recent study on supporting new special education teachers?

Wilkerson: One thing that made a big difference is when the teachers in our study, which is now under review, had access to a mentor and a group of their peers. We called this facilitated peer-to-peer group of teachers a โ€œcommunity of practice.โ€ Every other week, on Zoom, we’d get these new special education teachers from different school districts together, along with experienced teachers. And they would do some sort of work on problems, bringing in the things that were challenging, and work on possible solutions as a group.

We also used Zoom to do one-on-one mentoring. And what people liked about it was that they could to someone who wasn’t right in their building and right in their district who they could be open and vulnerable with.

Sometimes, special educators can be isolated because they’re not necessarily a part of a grade-level team. They work with kids across a lot of classrooms. This gave them an to have their own kind of community, and that made a difference.

We also surveyed their level of burnout and how good they felt about the job they did. And then we surveyed special education teachers who weren’t participating in our community of practice.

At the end of the year, those people who had that mentoring and the community of practice felt less burnt out, and they also felt more effective in the area of classroom management. And that’s critical, because burnout is one of the primary reasons people leave the profession.

So if we can make people feel like they’re better equipped to handle this challenging position, then that’s one strategy to increase the number of people wanting to stay in their job year after year.

Watch the full interview to hear more.

SciLine is a free service based at the American Association for the Advancement of Science, a nonprofit that helps journalists include scientific evidence and experts in their stories.The Conversation

Kimber Wilkerson, Professor of Special Education, University of Wisconsin-Madison

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