“Many people don’t realize that these conditions are very common in ambulatory care,” said Michigan Medicine gastroenterologist Shirley Ann Cohen-Mekelburg, M.D., who specializes in conditions like inflammatory bowel disease, Crohn’s disease and ulcerative colitis.

“Ultimately, this creates an excess in health care spending in the United States. Not only are these conditions debilitating for the millions of people living with them, but they’re also very expensive to treat.”

Cohen-Mekelburg says that in recent years, there has been a greater emphasis among providers in detecting why so many Americans are developing digestive diseases.

However, she notes that current approaches often fail to consider how things like psychosocial factors contribute to these conditions.

“As physicians, it’s important for us to pay attention to psychosocial factors involved in the lives of our patients, but they often go overlooked,” she said.

“These factors have the potential to significantly impact gastrointestinal health, and they also play a crucial role in the overall wellbeing of our patients.”

This notion inspired Cohen-Mekelburg and a team of fellow gastroenterologists and hepatologists to examine the rates of loneliness, depression and social isolation in older adults both with and without digestive diseases.

Their findings were recently published in Clinical Gastroenterology and Hepatology.

Cohen-Mekelburg notes that the team also “wanted to quantify these numbers with self-reported rates of poor health.”

“Our research involved analyzing data from 2008 to 2016 from the University of Michigan Health and Retirement Study.

This is a longitudinal panel study that involves a representative sample of approximately 20,000 individuals in the U.S. who are 50 years and older, as well as their spouses,” she said.

“It’s important to note that loneliness refers to the subjective distressed feeling of being alone or lacking companionship. The correlation between loneliness and depression is well established.”

However, Cohen-Mekelburg adds that social isolation refers to the “objective physical separation from other people, which is independent of psychological well-being.”

“Therefore, there are people who live in isolation but are well-adapted, not lonely and report high psychological wellbeing. But on the other hand, there are also people who are socially connected, yet suffer from low psychological wellbeing and loneliness. This, despite having a strong social network.”

Out of a pool of 7,110 participants, the team identified 56% of individuals with a digestive disease and 44% without one.

“Overall, 60.4% and 55.6% of respondents with and without digestive diseases reported loneliness, while 12.7% and 7.5% reported severe depression, and 8.9% and 8.7% reported social isolation, respectively,” said Cohen-Mekelburg.

“We found that individuals with a digestive disease were more likely to report ‘poor-or-fair’ health when compared to those without one. And among patients with a digestive disease, loneliness, as well as moderate to severe depression, were associated with greater odds of self-reporting ‘poor-or-fair’ health.”

Cohen-Mekelburg says that she hopes these findings eventually empower gastroenterologists to “screen patients for depression and loneliness,” in addition to their physical symptoms. “By doing this, providers can better establish care pathways for mental health treatment for their patients, which is hugely important,” she said.

“Our research shows that gastroenterologists are in a unique position to help their patients achieve good overall health. If you’re a clinician who also happens to treat older adults, even better. Being aware of the link between loneliness, depressive symptoms and digestive diseases can really benefit your patients from a holistic perspective.”

In this study, scientists from the Biology of Intracellular Bacteria Unit, led by Carmen Buchrieser at the Institut Pasteur, in collaboration with Sophie Jarraud, Head of the National Reference Center for Legionella in Lyon, analyzed the diversity and composition of the respiratory tract microbiome (bacteria, archaea, fungi and protozoa) in patients with pneumonia caused by the intracellular bacterial pathogen Legionella pneumophila for their entire hospitalization period. L. pneumophila is responsible for a severe pneumonia known as Legionnaires’ disease, which can be contracted by inhaling contaminated aerosols from artificial water sources such as showers, hot tubs or air conditioning systems. The fatality rate for Legionnaires’ disease varies from 5 to 40% depending on the clinical context and the region. Risk factors are old age, pre-existing lung conditions, smoking and immunosuppression, and around two-thirds of reported cases occur in men. Confirmed cases of Legionnaires’ disease in the European Union went from 4,693 cases in 2005 to 10,004 cases in 2021, an increase of 113%. One of the reasons for this sharp rise may be climate change, with higher water temperatures and more frequent and intense floods that allow Legionella to replicate more rapidly and to access human environments.

The team of scientists combined high-throughput bacterial, archaeal and fungal marker gene sequencing with a quantification approach to characterize how the respiratory tract microbiome developed in patients over the course of infection and as a result of hospital-related interventions (such as mechanical ventilation and administration of antibiotics). A unique cohort of 38 hospitalized patients with pneumonia caused by Legionella pneumophila was analyzed. “We discovered complex microbiome dynamics, where commensal and pathogenic microorganisms coexist, and the equilibrium among their abundance drives the microbiome to recovery or dysbiosis,” explains Carmen Buchrieser, lead author of the study and Head of the Institut Pasteur’s Biology of Intracellular Bacteria Unit. The scientists observed that early in hospitalization, microbiome diversity decreased and the pathogen L. pneumophila was killed by the antibiotic treatment. But the empty niche was soon occupied by other opportunistic species, often resistant to antimicrobials — a factor that should be considered in prevention strategies for secondary infections. The respiratory tract microbiomes with the highest bacterial and fungal loads also showed lower diversity and pathogen enrichment, indicating that high biomass could be a biomarker for secondary and/or co-infections. Finally, the scientists showed that Legionella biomass correlates with disease severity and comorbidities, suggesting that pathogen quantification should be included in patient monitoring. Clinical interventions such as mechanical ventilation or administration of certain types of antibiotics influence the microbiome composition and therefore also disease outcome.

“In this study we also discovered that fungi, archaea and protozoa may be resident and not merely transitory in the respiratory tract of hospitalized patients and that they might contribute to pneumonia progression. This requires further investigation. Our research therefore shows that the interaction between respiratory tract microbiome equilibrium, pathogen load dynamics and clinical interventions plays a crucial role in the recovery of patients with pneumonia,” concludes Carmen Buchrieser.

The findings, published online by Nature Scientific Reports, may help explain some of the molecular processes driving higher rates of the disease — especially more aggressive forms of it — in African American women. ER-positive breast cancer accounts for about 70%-80% of all breast cancer cases, and African American women are 40% more likely to die from it than white women, said Zeynep Madak-Erdogan, a professor of nutritional sciences and of food science and human nutrition at the University of Illinois Urbana-Champaign and co-author of the paper.

Ashlie Santaliz-Casiano, a then-graduate student at the university, was the first author of the study. Madak-Erdogan, the corresponding author, oversaw the project along with Jonna Frasor, a professor of physiology and biophysics at the U. of I. Chicago; and Dr. Kent F. Hoskins, a professor of medicine in the UIC College of Medicine and director of the UIC Familial Breast Cancer Program. Researchers at Northwestern University, Northwestern Memorial Hospital and Northeastern University were partners on the project.

“Overall, we are pretty good at managing the disease, early diagnosing cases with mammography and treating them with drugs that were developed several decades ago,” Madak-Erdogan said.

“Although the tumors are often caught at earlier stages, patients from lower-income neighborhoods such as Chicago’s South Side are more likely to have poor outcomes. That suggests there are some biological factors driving these differing effects,” she said.

The study population included African American women and non-Hispanic white women ages 20-79 who were recruited at three hospitals in the Chicago area in 2018-19.

The team collected blood samples from 102 patients who were newly diagnosed with ER-positive breast cancer in stages 1-3, and 148 healthy women served as the control group. The samples were collected from control group participants at the time they enrolled in the study and from the patients with ER-positive breast cancer prior to breast surgery or other cancer treatment.

“The participants were matched on characteristics such as similar tumor types, similar body mass indices or other factors so we could examine the effects of their neighborhoods and economic backgrounds,” Madak-Erdogan said.

The team analyzed 83 metabolites in the women’s blood and found that African American women with ER-positive breast cancer had decreased circulating levels of amino acids — including the antioxidant methionine — compared with women in the healthy control group. Conversely, non-Hispanic white patients with the disease had significantly higher levels of fatty acids compared with African American women and those in the healthy control group.

The team hypothesized that methionine might be needed in greater volume to support increased DNA methylation — a mechanism that controls which genes get expressed — in African American patients with the disease, Madak-Erdogan said.

Hypermethylation is a possible biological mechanism that might explain poorer disease outcomes in African American women, she said. Aberrant hypermethylation in DNA can occur in the promoter and enhancer regions of cancer-related genes, including tumor suppressors, silencing their expression.

“Using the Pan-Cancer Atlas, a database of 33,000 tumors classified by genetic similarity maintained by the Cancer Genome Atlas Program, we mapped the metabolites to epigenetic regulatory systems,” said Santaliz-Casiano, currently a postdoctoral researcher at the National Cancer Institute in the National Institutes of Health. “We identified 291 genes associated with methylation activities that were expressed at higher rates — 15 of them at statistically significant levels — in African American women with ER-positive breast cancer.”

Poorer survival rates among African American women with the disease — but not non-Hispanic white women — were associated with higher expression of the gene NELFE, a protein complex that regulates enzymes involved in transcriptional activities for downstream target genes, she said.

Tumor cells utilize amino acids as alternative fuels and as precursors for processes such as DNA synthesis, constructing new blood vessels and promoting tumor cells’ rapid growth and proliferation.

In a previousstudy, published in the journal Cancer Research in 2019, a group led by Madak-Erdogan found that higher blood levels of free fatty acids “rewired” cancer cells’ metabolism, activating pathways that promoted tumor growth and proliferation in postmenopausal obesity-related cancer. The current study extends that work by identifying key differences by race: While higher fatty acid levels are good predictors of ER-positive breast cancer in non-Hispanic white women, higher amino acid levels are better predictors of the disease in African American women.

“These metabolic differences might suggest that there would be different screening strategies that could identify worse types of breast cancers,” Madak-Erdogan said. “These assays might enable earlier diagnosis based on patients’ blood. I imagine that it would not be difficult to design a cost-effective blood test for this purpose.

“The current standard screening is mammography, but it requires costly, dedicated equipment, as well as technicians and other trained professionals. If we could come up with a test to diagnose breast cancers earlier, especially those with potentially worse outcomes, that might be useful in clinics with limited resources.”

The paper was co-written by Dhruv Mehta, a then-graduate student at the U. of I. Co-authors at the U. of I. Chicago were: Oana C. Danciu, associate director of clinical research and professor, U. of I. Cancer Center; epidemiology professor Garth H. Rauscher; graduate students Hariyali Patel and Landan Banks; resident Ayesha Zaidi; and then-business administration associate Jermya Buckley.

Co-authors at Northwestern University were: clinical lead operations manager Lauren Schulte, and students Deanna Taiym and Lauren Ro Weller, all at the Robert H. Lurie Comprehensive Cancer Center; and, at the Feinberg School of Medicine, associate Natalie Pulliam, radiology professor Sarah M. Friedewald, breast surgery professor Seema Khan, obstetrics and gynecology professor J. Julie Kim and hematology/oncology professor William Gradishar.

Scott Hegerty, professor of economics and chair of anthropology, geography and environmental studies at Northeastern Illinois University, also co-wrote the study.

Now, researchers at the University of Missouri are one step closer to making the T cell army stronger. In a recent study, conducted in the Roy Blunt NextGen Precision Health building, the researchers found that by manipulating one molecular signaling pathway in the T cells that participate in clearing influenza virus in the lungs, the strength and longevity of immunological memory produced can be improved.

This finding can potentially support the future development of more effective vaccines and therapeutics to combat influenza and other respiratory infections with the ultimate goal of increasing the body’s immunological memory, which can both prevent and lessen the severity of infections and reinfections.

Emma Teixeiro and Mark A. Daniels, associate professors in the MU School of Medicine, led the NIH-funded study, which involved unique mouse models of influenza infection.

“Immunologists like myself have always wondered why T cells in the lungs after influenza infection disappear so quickly,” Teixeiro said. “This research can help us solve that problem by increasing the amount of T cells that can fight against infection. In this study, we have identified novel ways to improve the generation and long-term maintenance of protective immunity against influenza, and that is by manipulating a molecular target known as the IKK2/NFkB signaling pathway.”

Teixeiro added that T cells can recognize parts of viruses that do not mutate, so if researchers can better understand how to strengthen the T cells and extend the timeframe when they can do their job appropriately, the body’s immune system will ultimately be better suited to fight against infection and lessen the severity.

While the influenza virus was the focus of this particular study, gaining knowledge of the underlying molecular mechanisms and signaling pathways that regulate memory in tissues can be helpful to improve therapeutics for patients with cancer, autoimmunity or other respiratory infections.

“By unveiling the biochemical and molecular secrets of these T cells, we can provide valuable information to other scientists who work on optimizing vaccine strategies,” Teixeiro said. “The good news is there are already clinical treatments that do target this particular pathway we identified, so this study is a big step in the right direction, but we still have a long way to go.”

“IKK2/NFkB signaling controls lung resident CD8⁺ T cell memory during influenza infection” was recently published in Nature Communications. Coauthors on the study include Curtis J. Pritzl, Dezzarae Luera, Karin M. Knudson, Michael J. Quaney, Michael J. Calcutt and Mark A. Daniels.