Tag Archives: type 1 diabetes

Microbiology

Study finds sugary beverages increase dementia risk, while natural juices may help prevent it

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Dr. Liji Thomas, MDBy Dr. Liji Thomas, MDApr 17 2023Reviewed by Danielle Ellis, B.Sc.

In an article published in the journal Current Opinion in Microbiology, scientists have provided a detailed overview of the factors affecting maternal gut microbiota during pregnancy and its impact on maternal and infant health.

Study: Sugary beverages and genetic risk in relation to brain structure and incident dementia: a prospective cohort study. Image Credit: Africa Studio / ShutterstockStudy: Sugary beverages and genetic risk in relation to brain structure and incident dementia: a prospective cohort study. Image Credit: Africa Studio / Shutterstock

Background

Pregnancy is associated with a wide range of hormonal, immunological, and metabolic changes needed for fetal development. The most notable changes include increased cardiac output, higher levels of T regulatory cells, and alteration in gut microbiome composition.

Alteration in gut microbiota composition and diversity is associated with changes in women’s metabolic, immunological, and neurological processes, irrespective of pregnancy status. In addition, changes in gut microbiota composition are known to affect insulin sensitivity. In children with type 1 diabetes, functional and metabolic changes in gut microbiota have been documented.

Alteration in gut microbiota during pregnancy

Only limited evidence is available to thoroughly understand the changes in gut microbiota during pregnancy and its impact on maternal and fetal health. However, according to the available literature, low-grade inflammation at the intestinal mucosa as well as hormonal changes, might be responsible for gut microbiota alteration during pregnancy.

Regarding hormonal changes, pregnancy-related induction in progesterone levels is known to directly associate with increased Bifidobacterium levels in women. Bifidobacterium is a beneficial bacterium that naturally resides in the intestine. Therefore, the gut-to-gut transmission of this bacterium from the mother to the infant is crucial during the neonatal period. In infants, this bacterium helps degrade human milk oligosaccharides coming from maternal milk, in addition to developing infant gut microbiota and immune system.

Factors influencing maternal gut microbiota during pregnancy

Adult human gut microbiota can be influenced by many factors, including body mass index (BMI), medications, diseases, environment, and lifestyle (diet, physical activity, smoking, and drinking habits). Pre-pregnancy exposure to these factors can lead to structural and functional alteration in maternal gut microbiota during pregnancy.

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Animal studies have shown that maternal diet influences maternal and infant gut microbiota composition before and during pregnancy. Both pre-pregnancy body weight and pregnancy-related weight gain have been found to alter the composition and diversity of maternal gut microbiota.

Infant gut microbiota are influenced by the way they are delivered. For example, infants delivered vaginally have been shown to gain beneficial changes in gut microbiota compared to those delivered by c-section.

Functional studies in animals have shown that smoking-related nicotine exposure during pregnancy affects maternal gut microbiota, which in turn alters fetal exposure levels to circulating short-chain fatty acids and leptin during in-utero development.

Certain diseases before pregnancy, such as inflammatory bowel disease, have been found to influence maternal microbiota during pregnancy. The microbiota of the pregnant mother’s gut has also been shown to be affected pre-pregnancy and during pregnancy by certain medications, including antibiotics, proton-pump inhibitors, metformin, laxatives, and probiotics.

Maternal health impact of altered gut microbiota

Studies have found maternal gut microbiota alteration during pregnancy is associated with pregnancy complications, including gestational diabetes and preeclampsia.  

Gestational diabetes

A spontaneous induction in blood glucose levels during pregnancy is medically termed gestational diabetes. Studies have shown that a reduced abundance of beneficial bacteria and an increased abundance of pathogenic bacteria are responsible for the onset of gestational diabetes.

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In the microbiome of gestational diabetes patients, an increased abundance of membrane transport, energy metabolism, lipopolysaccharides, and phosphotransferase system pathways has been observed. Recent evidence indicates that gut microbiota-derived dopamine deficiency in the blood, impaired production of short-chain fatty acids, and excessive metabolic inflammation are collectively responsible for the development of gestational diabetes.

Preeclampsia

Preeclampsia is characterized by new-onset hypertension, proteinuria, and organ dysfunction during pregnancy. Studies involving pregnant women with preeclampsia have found gut microbiota dysbiosis (imbalance in gut microbiota composition) and increased plasma levels of lipopolysaccharide and trimethylamine N-oxide.

Recent evidence indicates that preeclampsia onset is associated with reduced bacterial diversity in gut microbiota. Specifically, the changes in gut microbiota include a depletion in beneficial bacteria and an enrichment in opportunistic bacteria.

Some mechanistic studies have pointed out that gut microbiota dysbiosis induces immune imbalance and intestinal barrier disruption in pregnant women, leading to the translocation of bacteria to the intrauterine cavity, placental inflammation, and poor placentation. All these factors collectively contribute to the development of preeclampsia.

Infant health impact of altered gut microbiota

Alteration in maternal gut microbiota has been found to affect the fetus’s neurodevelopment via signaling microbially modulated metabolites to neurons in the developing brain. These changes can have long-term effects on an infant’s behaviors.

Maternal microbiota-derived metabolites such as short-chain fatty acids are known to shape the metabolic system of infants. Some evidence has also indicated that maternal gut microbiota influences an infant’s susceptibility to allergic diseases.

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Journal reference:
Microbiology

Factors shaping maternal gut microbiome during pregnancy and the impact on infant health

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Dr. Sanchari Sinha Dutta, Ph.D.By Dr. Sanchari Sinha Dutta, Ph.D.Apr 17 2023Reviewed by Emily Henderson, B.Sc.

In an article published in the journal Current Opinion in Microbiology, scientists have provided a detailed overview of the factors affecting maternal gut microbiota during pregnancy and its impact on maternal and infant health.

Study: The maternal gut microbiome during pregnancy and its role in maternal and infant health. Image Credit: Design_Cells / ShutterstockStudy: The maternal gut microbiome during pregnancy and its role in maternal and infant health. Image Credit: Design_Cells / Shutterstock

Background

Pregnancy is associated with a wide range of hormonal, immunological, and metabolic changes needed for fetal development. The most notable changes include increased cardiac output, higher levels of T regulatory cells, and alteration in gut microbiome composition.

Alteration in gut microbiota composition and diversity is associated with changes in women’s metabolic, immunological, and neurological processes, irrespective of pregnancy status. In addition, changes in gut microbiota composition are known to affect insulin sensitivity. In children with type 1 diabetes, functional and metabolic changes in gut microbiota have been documented.

Alteration in gut microbiota during pregnancy

Only limited evidence is available to thoroughly understand the changes in gut microbiota during pregnancy and its impact on maternal and fetal health. However, according to the available literature, low-grade inflammation at the intestinal mucosa as well as hormonal changes, might be responsible for gut microbiota alteration during pregnancy.

Regarding hormonal changes, pregnancy-related induction in progesterone levels is known to directly associate with increased Bifidobacterium levels in women. Bifidobacterium is a beneficial bacterium that naturally resides in the intestine. Therefore, the gut-to-gut transmission of this bacterium from the mother to the infant is crucial during the neonatal period. In infants, this bacterium helps degrade human milk oligosaccharides coming from maternal milk, in addition to developing infant gut microbiota and immune system.

Factors influencing maternal gut microbiota during pregnancy

Adult human gut microbiota can be influenced by many factors, including body mass index (BMI), medications, diseases, environment, and lifestyle (diet, physical activity, smoking, and drinking habits). Pre-pregnancy exposure to these factors can lead to structural and functional alteration in maternal gut microbiota during pregnancy.

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Animal studies have shown that maternal diet influences maternal and infant gut microbiota composition before and during pregnancy. Both pre-pregnancy body weight and pregnancy-related weight gain have been found to alter the composition and diversity of maternal gut microbiota.

Mode of delivery has been found to influence infant gut microbiota. For example, infants delivered vaginally have been shown to gain beneficial changes in gut microbiota compared to those delivered by c-section.

Functional studies in animals have shown that smoking-related nicotine exposure during pregnancy affects maternal gut microbiota, which in turn alters fetal exposure levels to circulating short-chain fatty acids and leptin during in-utero development.

Certain diseases before pregnancy, such as inflammatory bowel disease, have been found to influence maternal microbiota during pregnancy. Similarly, pre-pregnancy and during-pregnancy consumption of certain medications, including antibiotics, proton-pump inhibitors, metformin, laxatives, and probiotics, has been found to influence maternal gut microbiota during pregnancy.

Maternal health impact of altered gut microbiota

Studies have found maternal gut microbiota alteration during pregnancy is associated with pregnancy complications, including gestational diabetes and preeclampsia.  

Gestational diabetes

A spontaneous induction in blood glucose levels during pregnancy is medically termed gestational diabetes. Studies have shown that a reduced abundance of beneficial bacteria and an increased abundance of pathogenic bacteria are responsible for the onset of gestational diabetes.

if (g_displayableSlots.mobileBottomMrec) {
pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-bottom-mrec’); });
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In the microbiome of gestational diabetes patients, an increased abundance of membrane transport, energy metabolism, lipopolysaccharides, and phosphotransferase system pathways has been observed. Recent evidence indicates that gut microbiota-derived dopamine deficiency in the blood, impaired production of short-chain fatty acids, and excessive metabolic inflammation are collectively responsible for the development of gestational diabetes.

Preeclampsia

Preeclampsia is characterized by new-onset hypertension, proteinuria, and organ dysfunction during pregnancy. Studies involving pregnant women with preeclampsia have found gut microbiota dysbiosis (imbalance in gut microbiota composition) and increased plasma levels of lipopolysaccharide and trimethylamine N-oxide.

Recent evidence indicates that preeclampsia onset is associated with reduced bacterial diversity in gut microbiota. Specifically, the changes in gut microbiota include a depletion in beneficial bacteria and an enrichment in opportunistic bacteria.

Some mechanistic studies have pointed out that gut microbiota dysbiosis induces immune imbalance and intestinal barrier disruption in pregnant women, leading to the translocation of bacteria to the intrauterine cavity, placental inflammation, and poor placentation. All these factors collectively contribute to the development of preeclampsia.

Infant health impact of altered gut microbiota

Alteration in maternal gut microbiota has been found to affect the fetus’s neurodevelopment via signaling microbially modulated metabolites to neurons in the developing brain. These changes can have long-term effects on an infant’s behaviors.

Maternal microbiota-derived metabolites such as short-chain fatty acids are known to shape the metabolic system of infants. Some evidence has also indicated that maternal gut microbiota influences an infant’s susceptibility to allergic diseases.

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Journal reference:
Microbiology

First clinical trial of GABA/GAD focused exclusively on children with recent onset Type 1 diabetes

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Reviewed by Emily Henderson, B.Sc.Feb 22 2023

For the first time, humans with newly diagnosed Type 1 diabetes, or T1D, have received two treatments called GABA and GAD that have shown promise in animal studies and in isolated human pancreas islets. This investigator-initiated clinical trial, published in Nature Communications, focused exclusively on children with recent onset T1D.

Diabetes is a disease affecting two pancreatic hormones -; insulin and glucagon. In healthy people, insulin helps cells take up glucose from the blood when glucose levels are high. In contrast, glucagon helps the liver release glucose into the bloodstream when glucose levels are low. Thus, levels of blood glucose remain steady.

In T1D, autoantibodies destroy the pancreatic beta cells, insulin release is diminished, and glucagon release is excessive relative to the insulin deficiency. This can cause a vicious cycle of escalating blood glucose levels. Strategies to ameliorate or cure T1D, therefore, target the preservation of insulin-secreting beta cells and/or attenuation of the relative excess of alpha cell glucagon. Most importantly, concerning the inhibition of alpha cell glucagon in this trial by GABA/GAD, recent studies in animals made diabetic have shown that inhibition of glucagon leads to expansion of insulin-secreting beta cells and improvements in hyperglycemia.

Researchers in the study, led by University of Alabama at Birmingham physicians, were able to enroll children within the first five weeks of diagnosis, before the near total eradication of beta cells. Forty percent of the study participants were younger than 10 years old. The study -; which was constrained to lower-dose GABA therapy by the United States Food and Drug Administration because it was the first human trial with GABA -; did not achieve its primary outcome, the preservation of insulin production by beta cells. However, it did meet the clinically relevant secondary outcome of reduced serum glucagon. Significantly, the trial confirmed the safety and tolerability of oral GABA. Additionally, in collaboration with the immunology team of Hubert Tse, Ph.D., at the UAB Comprehensive Diabetes Center, a separate manuscript under review will describe a salutary effect of GABA alone and in combination with GAD on cytokine responses in peripheral blood mononuclear cells from trial participants.

GABA is gamma aminobutyric acid, a major inhibitory neurotransmitter. In the endocrine pancreas, GABA participates in paracrine regulation -; meaning a hormone that acts on nearby cells -; on the beta cells that produce insulin and the alpha cells that produce glucagon. In various mouse model studies, GABA was able to delay diabetes onset, and restore normal blood glucose levels after diabetes had already commenced. GABA treatment also led to significant decreases in the inflammatory cytokine expression that participates in the pathogenesis of T1D.

GAD is glutamic acid decarboxylase, the enzyme that acts on glutamate to form GABA. Animal and pancreatic islet cell studies show that immunization with GAD alone may help preserve beta cells. Both GABA and GAD are highly concentrated in the pancreatic islet, which is the autoimmune target of T1D.

The study, which was conducted between March 2015 and June 2019, screened 350 patients and enrolled 97, whose ages averaged 11 years. Forty-one took oral GABA twice a day; 25 took the oral GABA in combination with two injections of GAD, one at the baseline visit and one at the one-month visit. The remaining 31 children received a placebo treatment. Analysis after one year of treatment included 39 in the GABA group, 22 in the GABA/GAD group and 30 in the placebo group.

Given that GABA reduces immune inflammation at higher doses in several diabetic rodent models, it is plausible that increased GABA doses, or longer-acting preparations, could offer sufficiently prolonged, above-threshold GABA concentrations to preserve islet cells, particularly during stage 1 diabetes.”

Gail Mick, M.D., UAB Professor in the Department of Pediatrics’ Division of Pediatric Endocrinology and Diabetes

Mick and Kenneth McCormick, M.D., who recently retired from UAB Pediatrics, co-led the trial.

Alexandra Martin and Mick, UAB Department of Pediatrics, are co-first authors of the study, “A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes.”

Other authors are Heather M. Choat, Alison A. Lunsford and Kenneth L. McCormick, UAB Department of Pediatrics; Hubert M. Tse, UAB Department of Microbiology; and Gerald G. McGwin Jr., Department of Epidemiology, UAB School of Public Health.

Source:

University of Alabama at Birmingham

Journal reference:

Martin, A., et al. (2022) A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes. Nature Communications. doi.org/10.1038/s41467-022-35544-3.

Microbiology

Research project obtains nearly seven million to study factors that affect human immune system in early life

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Dec 2 2022Reviewed by Aimee Molineux

The first few months and years of life are crucial to the development of the human immune system. This is an important phase as the immune system can define which diseases individuals might develop later in life. INITIALISE, a joint research project of ten universities, will study which environmental factors and mechanisms modify the human immune system in early life and whether targeted interventions could have a positive impact. The project obtained nearly seven million in funding from Horizon Europe.

Research project obtains nearly seven million to study factors that affect human immune system in early life
Professor Matej Orešič. Image Credit: Photographer/Author- Jasper Mattson, Örebro University

The research project is led from the University of Turku and it is coordinated by Professor Matej Orešič, who is also a group leader in the InFLAMES research flagship at the University of Turku, Finland.

The development of the human immune system starts already in the womb and continues after birth once the child is exposed to numerous bacteria, viruses, and other environmental factors. Exposure is important to the development of the immune system, but this stage of development is not without its risks.

“The first few months and years are a very delicate and vulnerable time. We already know that the development of the human immune system in early life is connected to the risks of several diseases later on, particularly allergies, asthma, and autoimmune diseases, such as type 1 diabetes. Yet, the mechanisms of immune imprinting in early life are still poorly understood,” says Professor Matej Orešič.

In a collaboration between ten universities, the INITIALISE project (Inflammation in human early life: targeting impacts on life-course health) will investigate which factors have an impact on the development of the human immune system and what is its significance for people’s health throughout the course of their lives.

A key question is if the immune system be modified so that the risks for different diseases would decrease.    

“Our shared view is that effective early-life interventions targeting the immune system will have a positive impact on life-course health,” says Orešič.

Focus on the impact of chemical exposure

As the immune system starts developing already before birth, the INITIALISE researchers are also interested in the mother’s diet, chemical exposures, and stress during pregnancy. After birth, the intricate interplay of environmental factors and genetics begins and their impact on the development of the immune cells is not yet well understood. In addition, the gut bacteria developed at the beginning of life have an impact on people’s health throughout their entire lifespan.

Furthermore, children have to face the chemical load in their environment with a still developing immune system.

“We are going to study how chemicals impact the immune system. Even a small exposure to chemicals can have significant consequences, and this also applies to other factors that shape our immune system. This is due to the fact that in our first few years, we develop and change quickly and constantly,” Orešič explains. 

INITIALISE mobilises clinicians and scientists with diverse and complimentary expertise in immunology, paediatrics, microbiology, and metabolism. In addition, experts in metabolomics and lipidomics, proteomics, genetics, exposome, psychiatry, systems medicine, and bioinformatics participate in the study. 

Project lasts six years

INITIALISE includes eight prospective and longitudinal birth cohort studies, where the researchers follow groups of children for a long period of time to observe the development of immune-mediated diseases.

Towards the end of the research project, the researchers will conduct a clinical pilot study which aims to discover whether the immune system can be “altered” to prevent the development of diseases.

The clinical trial will target the gut microbiome in at-risk children. Our aim is to improve immune status and reduce disease risk.”

Professor Matej Orešič

The INITIALISE project starts at the beginning of 2023 and lasts six years. In addition to the University of Turku, the member organizations include Örebro University (SE), University of Naples Federico II (IT), Karolinska Institute (SE), University Medical Center Groningen (NL), Linköping University (SE), University of Helsinki (FI), University of Florida (US), Spanish National Research Council (ES), and University of Aberdeen (associated partner, UK).

Source:

University of Turku