Posted on Diabetes

Gut bacteria may play a role in diabetes

One type of bacteria found in the gut may contribute to the development of Type 2 diabetes, while another may protect from the disease, according to early results from an ongoing, prospective study led by investigators at Cedars-Sinai. 

The study, published in the peer-reviewed journal Diabetes, found people with higher levels of a bacterium called Coprococcus tended to have higher insulin sensitivity, while those whose microbiomes had higher levels of the bacterium Flavonifractor tended to have lower insulin sensitivity. 

For years, investigators have sought to understand why people develop diabetes by studying the composition of the microbiome, which is a collection of microorganisms that include fungi, bacteria and viruses that live in the digestive tract. The microbiome is thought to be affected by medications and diet. Studies have also found that people who don’t process insulin properly have lower levels of a certain type of bacteria that produce a type of fatty acid called butyrate. 

Mark Goodarzi, MD, PhD, the director of the Endocrine Genetics Laboratory at Cedars-Sinai, is leading an ongoing study that is following and observing people at risk for diabetes to learn whether those with lower levels of these bacteria develop the disease. 

“The big question we’re hoping to address is: Did the microbiome differences cause the diabetes, or did the diabetes cause the microbiome differences?”said Goodarzi, who is the senior author of the study and principal investigator of the multicenter study called Microbiome and Insulin Longitudinal Evaluation Study (MILES). 

Investigators involved in MILES have been collecting information from participating Black and non-Hispanic white adults between 40 and 80 years of age since 2018. An earlier cohort study from the MILES trial found that birth by cesarean section is associated with a higher risk for developing prediabetes and diabetes.

For the most recent study to come out of this ongoing trial, investigators analyzed data from 352 people without known diabetes who were recruited from the Wake Forest Baptist Health System in Winston-Salem, North Carolina.

Study participants were asked to attend three clinic visits and collect stool samples prior to the visits. Investigators analyzed data collected at the first visit. They conducted genetic sequencing on the stool samples, for example, to study the participants’ microbiomes, and specifically look for bacteria that earlier studies have found to be associated with insulin resistance. Each participant also filled out a diet questionnaire and took an oral glucose tolerance test, which was used to determine ability to process glucose.

Investigators found 28 people had oral glucose tolerance results that met the criteria for diabetes. They also found that 135 people had prediabetes, a condition in which a person’s blood-sugar levels are higher than normal but not high enough to meet the definition of diabetes. 

The research team analyzed associations between 36 butyrate-producing bacteria found in the stool samples and a person’s ability to maintain normal levels of insulin. They controlled for factors that could also contribute to a person’s diabetes risk, such as age, sex, body mass index and race. Coprococcus and related bacteria formed a network of bacteria with beneficial effects on insulin sensitivity. Despite being a producer of butyrate, Flavonifractor was associated with insulin resistance; prior work by others have found higher levels of Flavonifractor in the stool of people with diabetes. 

Investigators are continuing to study samples from patients who participated in this study to learn how insulin production and the composition of the microbiome change over time. They also plan to study how diet may affect the bacterial balance of the microbiome. 

Goodarzi emphasized, however, that it is too early to know how people can change their microbiome to reduce their diabetes risk.

“As far as the idea of taking probiotics, that would really be somewhat experimental,” said Goodarzi, who is also the Eris M. Field Chair in Diabetes Research at Cedars-Sinai. “We need more research to identify the specific bacteria that we need to be modulating to prevent or treat diabetes, but it’s coming, probably in the next five to 10 years.”

Posted on Diabetes, Obesity, Weight Loss

Time-restricted eating reshapes gene expression throughout the body.

Science image


Time-restricted eating reshapes gene expression throughout the body. In this illustration, the Ferris wheel displays the interconnected organ systems working smoothly during time-restricted eating, represented by the clock in the middle CREDIT Salk Institute

Numerous studies have shown the health benefits of time-restricted eating, including an increase in life span in laboratory studies, and practices like intermittent fasting, a hot topic in the wellness industry. However, how it affects the body on the molecular level and how those changes interact across multiple organ systems has not been well understood. Now, Salk scientists show in mice how time-restricted eating influences gene expression across more than 22 regions of the body and brain. Gene expression is the process through which genes are activated and responds to their environment by creating proteins.

The findings, published in Cell Metabolism on January 3, 2023, have implications for many health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer.

“We found that there is a system-wide, molecular impact of time-restricted eating in mice,” says Professor Satchidananda Panda, senior author and holder of the Rita and Richard Atkinson Chair at Salk. “Our results open the door for looking more closely at how this nutritional intervention activates genes involved in specific diseases, such as cancer.”

For the study, two groups of mice were fed the same high-calorie diet. One group was given free access to food. The other group was restricted to eating within a feeding window of nine hours each day. After seven weeks, tissue samples were collected from 22 organ groups and the brain at different times of the day or night and analyzed for genetic changes. Samples included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, different parts of the kidney and intestine, and different areas of the brain.

The authors found that 70 per cent of mouse genes respond to time-restricted eating.

“By changing the timing of food, we were able to change the gene expression not just in the gut or in the liver, but also in thousands of genes in the brain,” says Panda. 

Nearly 40 per cent of genes in the adrenal gland, hypothalamus, and pancreas were affected by time-restricted eating. These organs are essential for hormonal regulation. Hormones coordinate functions in different body and brain parts, and hormonal imbalance is implicated in many diseases, from diabetes to stress disorders. The results offer guidance on how time-restricted eating may help manage these diseases.

Interestingly, not all sections of the digestive tract were affected equally. While genes involved in the upper two portions of the small intestine—the duodenum and jejunum—were activated by time-restricted eating, the ileum, at the lower end of the small intestine, was not. This finding could open a new line of research to study how jobs with shiftwork, which disrupt our 24-hour biological clock (called the circadian rhythm) impact digestive diseases and cancers. Previous research by Panda’s team showed that time-restricted eating improved the health of firefighters, who are typically shifting workers.

The researchers also found that time-restricted eating aligned the circadian rhythms of multiple body organs.

“Circadian rhythms are everywhere in every cell,” says Panda. “We found that time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting and another just after eating. We suspect this allows the body to coordinate different processes.”

Next, Panda’s team will take a closer look at the effects of time-restricted eating on specific conditions or systems implicated in the study, such as atherosclerosis, which is a hardening of the arteries that is often a precursor to heart disease and stroke, as well as chronic kidney disease.

Posted on Rheumatoid arthritis

A promising drug delivery method could replace injections with pills


For chronic conditions such as rheumatoid arthritis, treatment often involves lifelong injections. Fear of needles, injection-associated infection and pain are responsible for patients skipping doses, which encourages the development of new delivery strategies that combine efficacy with limited side effects to treat patients adequately.

Researchers at Baylor College of Medicine and collaborating institutions have explored a better way of delivering medications that does not require injections but could be as easy as swallowing a pill. The study appears in the Proceedings of the National Academy of Sciences.

“People don’t like to have injections for the rest of their lives,” said co-corresponding author Dr. Christine Beeton, professor of integrative physiology at Baylor. “In the current work, we explored the possibility of using the probiotic bacteria Lactobacillus reuteri as a novel oral drug delivery platform to treat rheumatoid arthritis in an animal model.”

Previous work from the Beeton lab had shown that a peptide, or short protein, derived from sea anemone toxin effectively and safely reduces disease severity in rat models of rheumatoid arthritis and patients with plaque psoriasis. “However, peptide treatment requires repeated injections, reducing patient compliance, and direct oral delivery of the peptide has low efficacy,” Beeton said.

Beeton joined forces with Dr. Robert A. Britton, professor of molecular virology and microbiology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. The Britton lab has developed the tools and expertise to genetically modify probiotic bacteria to produce and release compounds. In the current study, the team bioengineered the probiotic L. reuteri to secrete peptide ShK-235 derived from sea anemone toxin.

They chose L. reuteri because these bacteria are indigenous to human and other animal guts. It is one of the lactic acid bacteria groups that has long been used as a cell factory in the food industry and is recognized as safe by the U.S. Food and Drug Administration. L. reuteri has an excellent safety profile in infants, children, adults and even in an immunosuppressed population.

“The results are encouraging,” Beeton said. “Daily delivery of these peptide-secreting bacteria, called LrS235, dramatically reduced clinical signs of disease, including joint inflammation, cartilage destruction and bone damage in an animal model of rheumatoid arthritis.”

The researchers followed bacteria LrS235 and the peptide ShK-235 it secretes inside the animal model. They found that after feeding rats live LrS235 that release ShK-235, they could detect ShK-235 into the blood circulation.

“Another reason we chose L. reuteri is that these bacteria do not remain in the gut permanently. They are removed as the gut regularly renews its inner surface layer to which the bacteria attach,” Beeton said. “This opens the possibility for regulating treatment administration.”

More research is needed to bring this novel drug delivery system into the clinic, but the researchers anticipate that it could make treatment easier for patients in the future. “These bacteria could be stored in capsules that can be kept on the kitchen counter,” Beeton said. “A patient could take the capsules when on vacation without the need of refrigeration or carrying needles and continue treatment without the inconvenience of daily injections.”

The findings provide an alternative delivery strategy for peptide-based drugs and suggest that such techniques and principles can be applied to a broader range of drugs and the treatment of chronic inflammatory diseases.

Posted on Multiple Sclerosis

Protein ‘anchors’ play a key role in neurotransmitter GABA action. Discovery could lead to new therapies for neurological disorders such as Multiple Sclerosis.

Travelling with multiple sclerosis

New clues about the way brain chemical transmitter GABA functions suggest that a protein ‘anchor’ plays a key role in helping position its receptors in nervous cells.

New research published in Nature Communications has found that a protein called Filamin A is responsible for guiding receptors to their correct places in brain cells. These receptors control brain activity in response to GABA, the main inhibitory neurotransmitter in the brain.

GABA plays a critical role in the brain including controlling bodily movements and the transmission of pain. By activating specific receptors in the brain, GABA maintains proper brain activity by slowing down electric impulses as they travel between brain cells.

The discovery that protein Filamin A is involved in positioning these receptors to the right place

could enable researchers to develop new therapies to manage a range of neurological disorders including Multiple Sclerosis.

Davide Calebiro, Professor of Molecular Endocrinology at the University of Birmingham and lead author of the paper said:

“Filamin A answers a question that scientists have been asking about how GABA is able to control a range of functions in the brain. By acting like an anchor that precisely positions GABA-B receptors where they are needed, it allows GABA to modulate a whole host of brain functions that are implicated in multiple neurological diseases.

“While the GABA-A receptor get most of the attention as it mediates rapid GABA responses, twin brother B that mediates slower responses is a hugely potential drug target, and our findings could have significant impacts in treating everything from multiple sclerosis to epilepsy.

“Moreover, we hypothesise that defects in Filamin A could impair the normal localisation of GABA-B receptors in neurons, disrupting the correct processing of signals in the brain and ultimately leading to the brain not being able to communicate effectively with the rest of the body.”

Pioneering lab work

Filamin A’s role in GABA activity was found thanks to new pioneering research methods developed at the Centre of Membrane Proteins and Receptors (COMPARE), a research institute of the University of Birmingham in partnership with the University of Nottingham.

In particular, the use of single molecule and super resolution microscopy approaches developed by the Calebiro lab have enabled the research team to directly follow individual receptors and Filamin molecules as they interact on the surface of living cells with unprecedented detail.

Posted on Patient Talk

You Can Improve Your Health From Head to Toe With These Strategies

You Can Improve Your Health From Head to Toe With These Strategies

We are approaching the new year, and that means that people will be making their new year’s resolutions, and many of them will involve living a healthier life. The good news is that there are many easy strategies that you can begin today that can help you to live your best life, and you can achieve them all with effort and persistence. Here at Patient Talk, we love to help people of all ages and characteristics live their best lives, so we have some tips that you can implement today to have a healthier life.

Start By Eliminating Stress From Work and Consider Online College

Many times we dread a new year because we know that we will be returning to the same job that has been causing us stress every day. If this is the case, then make 2023 a chance to find a career that can make you feel fulfilled day after day. One way that you can ensure a successful transition is by going to school online. This is a great way to take your classes on your own time so you can get a great degree and still keep working at your existing job.

There are many amazing degrees that can help you find a fulfilling career. One idea is to enroll in a bachelor of education program, which offers you many great opportunities to start a career as a teacher or to learn about early childhood education, and many other great options. Before going to a school, ensure that it is accredited and that you can find affordable rates that will fit in your budget.

Find Ways to Walk More Often

An easy way to ensure your physical and mental health is to walk whenever and wherever you can. When you walk, you get the blood flowing, and when you walk outside, you get a chance to clear your head so you can get rid of your anxiety. Look for opportunities to walk, including when you go to the store, to work, and in the mornings when you need a workout.

Walking is especially important if you work from home in a sedentary job where you are sitting most of the day. In this case, you need to find reasons to walk. Make sure that you take your breaks and your lunch every day, and consider walking at those times. You could also walk to other offices to have lunch with your friends or organize a group of coworkers who go out walking together during breaks.

Get Enough Sleep Every Night

Another way to ensure your health from head to toe is to make it a point to get eight to nine hours of sleep every night. When you rest, you give your mind a chance to relax and refresh, so you wake up without anxiety. Also, sleeping helps your body to repair your immune system, which makes it less likely that you will get sick.

If you have trouble getting enough sleep, then you may need to reset your circadian rhythm. You can do that by going to bed and waking up at the same time every day, including on weekends. Also, avoid looking at your phone while you lay in bed, as the blue light can also disrupt your sleep. If you have trouble falling asleep, then read a book or put on relaxing music.

As you can see, there are several strategies that you can try to live the healthiest life possible in 2023 and beyond. Remember to prioritize walking more often, find ways to get enough sleep, and consider returning to school and earning an online degree so you can find that dream job and you’ll be truly happy. If you would like to know more about the help we can provide at Patient Talk, then please contact us at info@patienttalk.org.