Health is wealth as the saying goes and new research now shows that it is possible to have a healthy, less stressed society through familiar and inexpensive foods. One such food might be the Japanese natto which is made from softened soybeans that have been boiled or steamed and fermented with a bacteria called Bacillus subtilis var. natto. Bacillus subtilis var. natto is found in soil, plants, animals, and the human stomach and intestines. Most of the natto consumed in Japan is made from the Miyagino strain.
A research group led by Professor Eriko Kage-Nakadai at the Graduate School of Human Life and Ecology, Osaka Metropolitan University, examined the effects of Bacillus subtilis var. natto consumption on the lifespan of the host using Caenorhabditis elegans worms. The researchers found that Caenorhabditis elegans fed Bacillus subtilis var. natto had a significantly longer lifespan than those fed the standard diet, and further elucidated that the p38 MAPK pathway and insulin/IGF-1-like signaling pathway, which are known to be involved in innate immunity and lifespan, were involved in the lifespan-enhancing effects of Bacillus subtilis var. natto. They also examined stress tolerance, which has been shown to have a correlation with longevity, and found that resistance to UV light and oxidative stress is enhanced.
For the first time, we were able to demonstrate the possibility of lifespan-extending effects of Caenorhabditis elegans through the ingestion of Bacillus subtilis var. natto. We hope that future experiments on mammals and epidemiological studies will help to realize a healthy and longer-living society if we can apply this research to humans.”
Professor Eriko Kage-Nakadai, Graduate School of Human Life and Ecology, Osaka Metropolitan University
The research results were published online in the Journal of Applied Microbiology on April 20, 2023.
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Teramoto, N., et al. (2023) Impacts of Bacillus subtilis var. natto on the lifespan and stress resistance of Caenorhabditis elegans.Journal of Applied Microbiology. doi.org/10.1093/jambio/lxad082.
A team led by LMU chemist Lena Daumann has demonstrated for the first time that bacteria can use certain radioactive elements to sustain their metabolism.
As well as being a useful material in all kinds of key technologies, lanthanides are important for bacteria, which use the rare earth metals in their metabolism. It turns out, however, that they are not as irreplaceable as previously thought, as an international and interdisciplinary team led by Professor Lena Daumann from the Department of Chemistry at LMU has demonstrated: Certain bacteria can use the radioactive elements americium and curium instead of the lanthanides — and even prefer them sometimes.
Bacteria that use lanthanides are widespread in the environment. They belong to the so-called methylotrophs, which can use methanol or methane as carbon and energy sources. To do this, they take up lanthanides and incorporate them into an important metabolic enzyme, a lanthanide-dependent methanol dehydrogenase. The elements americium and curium, members of the radioactive actinides, are very similar to the lanthanides when it comes to key chemical properties such as size and charge. “And so we asked ourselves whether the bacteria can use actinides instead of their essential lanthanides,” says Daumann.
Now the researchers have demonstrated that this is actually the case. They carried out an in-vivo study of two methylotrophic bacterial strains in collaboration with the Helmholtz Center in Dresden-Rossendorf (HZDR). “We fed the microbes various elements and showed that they incorporate americium and curium and grow just as well with these elements,” explains Daumann. It is important that the actinides have the same oxidation state and are of a similar size to the lanthanides normally used, so that they fit in the active center of methanol dehydrogenase. Additional in-vitro studies with isolated methanol dehydrogenase also demonstrate that the enzyme works with the actinides and exhibits similar activities.
“We could thus show for the first time that organisms can use these radioactive elements for life processes,” emphasizes Daumann. When the bacteria were offered a mixture of various lanthanides and actinides, they even preferred americium and curium ahead of some lanthanides. The ability of the bacteria to incorporate radioactive actinides is also interesting with respect to potential applications: “Methylotrophic bacteria could potentially be used in bioremediation or in the separation and recycling of lanthanides and actinides. Such difficult-to-separate mixtures are often found in spent nuclear fuel,” says Daumann.
Helena Singer, Robin Steudtner, Andreas S. Klein, Carolin Rulofs, Cathleen Zeymer, Björn Drobot, Arjan Pol, N. Cecilia Martinez‐Gomez, Huub J. M. Op den Camp, Lena J. Daumann. Minor Actinides Can Replace Essential Lanthanides in Bacterial Life**. Angewandte Chemie International Edition, 2023; DOI: 10.1002/anie.202303669
In a recent study published in the journal Nature Microbiology, researchers investigated whether intestinal microbial alterations contribute to anorexia nervosa (AN) pathogenesis.
AN, a disorder associated with altered eating, has caused considerable mortality, especially among women. However, therapies based on scientific evidence are scarce. AN pathogenesis likely involves several environmental and genetic factors. Studies have reported intestinal microbial dysbiosis among AN-affected individuals. However, data were obtained from small sample sizes, and genus-level microbial alterations were analyzed by amplicon sequencing.
In the present study, researchers assessed the association between the intestinal microbiome and AN.
The team performed metabolomics and shotgun metagenomic analyses on serum and fecal samples, respectively, that were obtained from women with AN (n=77) and age- and sex-matched healthy controls (n=70). Further, the fecal microbiome was transplanted from anorexia nervosa cases to murine animals fed calories-limited diets over three weeks to simulate AN eating behavior for in vivo analysis. In addition, the team explored causal associations in silico by bidirectional mediation analysis. The intestinal microbiome was analyzed at functional, taxonomic, and genetic levels.
The team used the eating disorder inventory-3 (EDI-3) questionnaire to assess eating behaviors and insulin resistance was assessed using the homoeostatic model assessment for insulin resistance (HOMA-IR) tool. The team examined covariations between bacterial abundance at species and genus levels and clinical variables for AN cases and controls. Linear regression modeling was performed, adjusting for confounders such as age, smoking status, medications, and body mass index (BMI).
Further, the team evaluated the growth dynamics of gut bacteria by calculating peak-to-trough ratios (PTR) using the metagenomic dataset. The functional modules of gut bacteria were identified using gut-brain modules (GBMs) and gut metabolic modules (GMMs). Differences in bacterial genomics were explored based on the Canberra distance of bacterial structural variant profiles.
Graphical abstract of the study workflow and findings.
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Results
Several bacterial organisms (including Clostridium) were altered among individuals with anorexia nervosa and were associated with mental well-being and eating behavior estimates. Bacterial functional-type modules related to neurotransmitter degradation were enriched among those with anorexia nervosa. Further, several structural variants (SVs) in bacterial organisms were associated with the metabolic characteristics of anorexia nervosa.
The findings indicated a probable role of the intestinal microbiome in AN-associated changes concerning satiety and the metabolism of secondary bile acids. The metabolomic analysis indicated an elevation in metabolites linked to lowered food consumption (including taurine-hyodeoxycholic acid, taurine-α-muricholic acid, and indole-3-propionic acid molecules). Causal inference analysis indicated that serological bacterial metabolites probably mediate the effect of gut microbial alterations on anorexia nervosa. At the phylum level, AN microbiome samples showed lowered Actinobacteriota and Bacteroidota counts. Among families of bacteria, Christensenellaceae species, particularly CAG-138, showed the most significant enrichment in AN.
At the genus level, elevated Lactobacillus counts were observed in the AN microbiota. The Ruminococcacea-enterotype was more prevalent in cases of AN. Species-level analysis indicated greater β-diversity among AN-affected women. In AN, Roseburia inulinivorans and Roseburia intestinalis were depleted, whereas those of Erysipelatoclostridium ramosum, Blautia species CAG, and Enterocloster bolteae innocuum (Clostridium) were increased. Clostridium counts correlated positively with eating disorder scores. The abundance of Bifidobacterium and Parasutterella, in absolute terms, showed positive correlations with perfectionism and body dissatisfaction, respectively.
Absolute Brachyspira count showed a positive association with ‘drive for thinness’ markers in anorexia nervosa. Median values for PTR markedly differed between individuals with AN and controls. Women with AN were leaner, had lower fasting serological insulin, glucose, and C-reactive protein (CRP) levels, and were more sensitive to insulin than controls. Bacterial organisms with significant growth retardation, among AN case individuals included Alistipes finegoldii,Akkermansia muciniphila, Eubacterium siraeum, Coprococcus catus, SS3/4, and Odoribacter splanchnicus.
In addition, the intestinal virome was altered among AN-affected individuals, including lowered bacterial-viral interactions, due to attenuated interactions of viruses with short-chain fatty acid (SCFA)-producing bacteria, including Roseburia inulinivorans, Roseburia hominis, and Faecalibacterium prausnitzii. The team observed greater viral richness and Shannon diversity in the fecal samples of AN cases compared to controls. Notably, 25/30 viruses increased in AN were Lactococcus bacteriophages. The abundance of GBMs for serotonin synthesis and degradation of tryptophan, glutamate, and dopamine, were enriched in AN.
The team detected 2,423 and 5,056 variable SVs and deletion SVs, respectively, across 56 species of bacteria, including Bacteroides uniformis, Faecalibacterium prausnitzii, Parabacteroides distasonis, Methanobrevibacter smithii. Individuals with AN lacking the genomic region of B. uniformis had greater scores for self-denial and bulimia. The genetic deletion in B. uniformis could result in the deficiency of thiamine, a vitamin associated with intestinal and mental health. The serotonin synthesis module causally affected BMI through glycoursodeoxycholic acid, which is upregulated by serotonin.
Serum leucine mediated the influence of B. vulgatus counts on glucose homeostasis. Mice receiving AN individuals’ fecal transplants initially lost more weight with a slower gain of weight with time than those receiving fecal transplants of control individuals. The finding was related to greater levels of hypothalamic appetite-suppressing genes and thermogenesis-associated genes in the adipose tissues of mice receiving fecal transplants from individuals with AN.
Based on the study findings, gut microbial disruptions may contribute to the pathogenesis of AN.
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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.
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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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.
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.
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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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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.
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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.
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.
Humans carry around trillions of microbes in their gastrointestinal tracts, and research has shown that the gut microbiome is closely linked to health. Studies have found that gut microbiomes are more healthy when they are made up of more diverse microbes, for example, and imbalances in the microbiome, or dysbiosis, is associated with disease. Scientists are now starting to look more closely at the specific types of microbes in the gut, and exactly how certain strains are influencing the development of specific disorders. A new report in Diabetes has identified two strains of gut microbes that seem to affect insulin sensitivity.
A multitude of studies have associated the microbiome with metabolic disease. For example, research has indicated that people who have lower levels of bacteria that generate butyrate, a fatty acid, also don’t process insulin correctly.
In this new study, a bacterium called Coprococcus was found at higher levels in people who tended to have more sensitivity to insulin, while higher levels of a bacterium called Flavonifractor were found in those who tended to be less insulin sensitive. Coprococcus may be protecting people from type 2 diabetes while Flavonifractor could be promoting the development of type 2 diabetes.
But it’s also important to decipher whether microbes can cause disease, or if differences in the microbiome arise after the disease is present. Senior study author Mark Goodarzi, MD, Ph.D., the director of the Endocrine Genetics Laboratory at Cedars-Sinai, is also the principal investigator of a multicenter study called Microbiome and Insulin Longitudinal Evaluation Study (MILES), which is aiming to determine whether factors in the microbiome cause diabetes, or if diabetes changes the microbiome.
Since 2018, MILES researchers have been assessing data from Black and non-Hispanic white adults who are 40 to 80 years old. In this study, the focus was on 352 study volunteers who had not been diagnosed with diabetes. These volunteers gave stool samples, did glucose tolerance tests, and supplied other information such as data about dietary habits. In this group, 135 were found to have prediabetes and 28 people had glucose tolerance tests that met the threshold for a diabetes diagnosis.
The researchers examined 36 gut bacteria that generate butyrate in the study participants (from the stool samples), and found that Coprococcus and related bacteria are good for insulin sensitivity.
Although Flavonifractor also generates butyrate, it was associated with insulin resistance. This confirms previous research that has found higher Flavonifractor levels in diabetic people. These findings were significant after the researchers controlled for other factors that affect the development of diabetes, including sex, race, body mass index, and age.
The study authors cautioned, however that people should not yet try to change their microbiome to lower their risk of diabetes.
“As far as the idea of taking probiotics, that would really be somewhat experimental,” said Goodarzi. More research is needed to determine exactly which bacteria should be altered “… but it’s coming, probably in the next five to ten years.”
Now the researchers want to learn more about how diet changes the microbiome, and they are planning to follow up with study volunteers to learn more about changes in insulin resistance and the microbiome over time.
Individuals with type 1 diabetes are eight times more likely than others to have an enterovirus infection; the findings support ongoing research on vaccines to help prevent the development of type 1 diabetes.
A new study recently presented at the annual conference of the European Association for the Study of Diabetes in Stockholm, Sweden, reveals a high association between a common group of viruses and type 1 diabetes (T1D).
According to the Australian study, those with T1D had an eight-fold higher risk of contracting an enterovirus infection than people without the condition.
T1D is the most prevalent form of diabetes in children, and its prevalence has been rising globally in recent decades. The immune system attacks and destroys the insulin-producing beta cells in the pancreas of patients with the disease, preventing the body from making enough of the hormone to properly regulate blood sugar levels.
High blood sugar levels may reduce life expectancy and damage the kidneys, feet, eyes, heart, and eyes over time. Additionally, diabetic ketoacidosis, a disease that often occurs at the time of T1D diagnosis and involves the accumulation of dangerous substances known as ketones in the blood, may be fatal if not treated promptly.
Although the specific cause of the immune system’s response is still up for debate, it is generally accepted that a genetic predisposition and one or more environmental triggers, such as a viral infection, are involved.
Some of the strongest evidence for virus involvement points toward the enteroviruses. This very common group of viruses includes those that cause polio and hand, foot, and mouth disease (HFMD), as well as other types that cause milder, cold-like symptoms.
Vaccines that seek to reduce the incidence of T1D by preventing enterovirus infection are already in clinical trials1 and confirmation of the role of enteroviruses would support this and other work toward the primary prevention of T1D.
To explore the association more deeply, Sonia Isaacs, of the Department of Paediatrics and Child Health, School of Clinical Medicine, University of New South Wales, Australia, and colleagues carried out a systematic review and meta-analysis of existing research on the topic.
The meta-analysis – the largest in this field – included data on 12,077 participants (age 0-87 years) from 60 controlled observational studies found on the PubMed and Embase databases.
5,981 of the participants had T1D or islet autoimmunity (which typically progresses to T1D). The remaining 6,096 participants had neither condition.
Enterovirus RNA or protein, a sign of a current or recent infection, was detected in blood, stool, or tissue samples using a range of advanced, and highly sensitive, molecular techniques.
Those with islet autoimmunity had twice the odds of testing positive for enteroviruses as those without islet autoimmunity.
The odds of enterovirus infection were eight times greater in those with T1D than in those without T1D.
Most importantly, individuals with T1D were over 16 times more likely to have an enterovirus infection detected in the month after their T1D diagnosis than those without T1D.
The researchers conclude that there is a clear association between enterovirus infection and both islet autoimmunity and T1D.
Ms. Isaacs adds: “These findings provide further support for ongoing work to develop vaccines to prevent the development of islet autoimmunity and therefore reduce the incidence of T1D.”
There are several theories about how enteroviruses increase the risk of developing T1D. It is thought, for example, that their interaction with particular genes may be important.
Ms. Isaacs explains: “Our study found that people with T1D who had both genetic risk and a first-degree relative with T1D were 29 times more likely to have an enterovirus infection.”
She continues, “The number, timing and duration, and even the site of enterovirus infections may also be important. The ‘leaky gut’ hypothesis suggests that viruses originating in the gut could travel along with activated immune cells to the pancreas, where a low-level, persistent infection and resulting inflammation can lead to an autoimmune response. Virus infections are also proposed to work in combination with other factors such as diet, imbalances in the gut microbiome, and even chemical exposures which may occur in utero (during pregnancy) or early childhood. There is still a lot to learn.”
Reference: This press release is based on abstract 236 at the annual meeting of the European Association for the Study of Diabetes (EASD). The material has been peer reviewed by the congress selection committee. The research will soon be submitted to a medical journal but the full paper is not yet available.
Bacteria known to cause oral infections may also be a contributory factor in patients developing potentially life-threatening abscesses on the brain, new research has shown.
The study, published in the Journal of Dentistry, investigated brain abscesses and their association with bacteria that occur in the oral cavity. While this type of abscess is relatively uncommon, it can result in significant mortality and morbidity.
Researchers examined the records of 87 patients admitted to hospital with brain abscesses, and used microbiological data obtained from abscess sampling and peripheral cultures.
This allowed them to investigate the presence of oral bacteria in patients’ brain abscesses where a cause of the abscess had either been found, as was the case in just 35 patients, or not found.
Their results showed that the 52 patients where no cause had been found were about three times as likely to have oral bacteria present in their samples.
Those patients also carried significantly higher counts of Streptococcus anginosus, a bacteria that can lead to pharyngitis, bacteremia, and infections in internal organs such as the brain, lung, and liver. This bacteria is often found in dental abscesses.
Writing in the study, researchers say the findings suggest that the oral cavity could be considered a source of infection in cases of brain abscess where no clear cause has been identified.
The research was led by the University of Plymouth and University Hospitals Plymouth NHS Trust.
Dr Holly Roy, an NIHR Clinical Lecturer in Neurosurgery based at the University of Plymouth and University Hospitals Plymouth NHS Trust, is the study’s lead author.
She said: “While many potential causes of brain abscesses are recognised, the origin of infection often remains clinically unidentified. However, it was still surprising to frequently find orally occurring bacteria in brain abscesses of unexplained origin. It highlights the importance of using more sensitive techniques to assess the oral cavity as a potential bacterial source in brain abscess patients. It also highlights the importance of improving dental care and oral hygiene more generally.”
The study forms part of ongoing research taking place within the University’s Oral Microbiome Research Group, led by Dr Raul Bescos and Dr Zoe Brookes, to explore the links between the oral microbiome and a range of cardiovascular and neurological conditions.
Other clinical trials are underway investigating the links between gum health and Alzheimer’s disease and identifying patients under high cardiovascular risk in primary care dental clinics, as an altered balance of oral bacteria (microbiome) during gum disease can lead to high blood pressure and strokes.
These clinical studies are being carried out in primary care dental facilities run by Peninsula Dental Social Enterprise, where the focus of the research is very much on improving clinical outcomes for patients.
Holly Roy, Raul Bescos, Ewen McColl, Umar Rehman, Elizabeth Cray, Louise A. Belfield, King-David Nweze, Kevin Tsang, William Singleton, Peter Whitfield, Zoe Brookes. Oral microbes and the formation of cerebral abscesses: A single-centre retrospective study. Journal of Dentistry, 2023; 128: 104366 DOI: 10.1016/j.jdent.2022.104366
A collaborative team led by researchers from Great Ormond Street Institute of Child Health (GOSH), London and including researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University and BOA Biomedical in Cambridge has re-engineered the process of microbial pathogen identification in blood samples from pediatric sepsis patients using the Wyss Institute’s FcMBL broad-spectrum pathogen capture technology. The advance enables accurate pathogen detection with a combination of unprecedented sensitivity and speed, and could significantly improve clinical outcomes for pediatric and older patients with bloodstream infections (BSIs) and sepsis. The findings were published in PLoS ONE.
BSIs with various microbial pathogens can rapidly escalate to life-threatening sepsis when the body is overwhelmed by the multiplying invaders and shuts down its organs’ functions. In 2017, there were 48.9 million cases and 11 million sepsis-related deaths worldwide. Importantly, almost half of all global sepsis cases occurred among children, with an estimated 20 million cases and 2.9 million global deaths in those under five years of age.
To prevent BSIs from progressing to full-blown sepsis, the infection-causing bacterial or fungal species must be identified as fast as possible. Only then can optimal pathogen-tailored antibacterial or antifungal treatments be applied in time. The conventional method used in clinical laboratories to identify the causative pathogenic species is long and laborious, requiring two time-consuming culture steps that take at least 1 to 3 days to complete.
“For all patients with sepsis, their chances of surviving dramatically shrink the longer it takes to identify the infection-causing pathogen(s) and thus, receive the most promising antimicrobial treatment,” said Nigel Klein, M.D., Ph.D., pls, a Professor of Infectious Disease and Immunology at GOSH, and a senior author on the study. “At Great Ormond Street Hospital we have been working to demonstrate both the importance rapid diagnosis and the fact that with innovative approaches we can identify the causative organism in between 40 minutes and six hours. Compared to adult patients, sepsis in infants and small children progresses much faster, and therefore there is a real need for diagnostic methods that support early detection. Accurate diagnosis is even more significant due to the availability of only small blood volumes from paediatric patients which can make re-sampling challenging.”
In 2020, senior authors Klein and Elaine Cloutman-Green, Ph.D., a Consultant Clinical Scientist and Infection Control Doctor at GOSH, began collaborating with Lead Staff Scientist Michael Super, Ph.D. and Founding Director Donald Ingber, M.D., Ph.D. at Harvard’s Wyss Institute to solve this problem. “Based on our earlier success with FcMBL in isolating pathogens from joints as well as bovine and human blood with extraordinary efficiencies, we hypothesized that building an FcMBL-mediated pathogen capture into a modified clinical blood culture protocol could shorten the time and reduce the size of the required patient samples to yield the same results that time-consuming blood culture protocols provide,” said Super.
In the pathogen identification process currently performed in clinical settings, first, blood samples are added to bottles containing liquid media in which infectious microbes, if present, are amplified to a certain density. Then, the amplified microbes are grown on solid media as isolated colonies whose constituent cells eventually can be identified with a highly sensitive, yet fast and relatively inexpensive analytical method know as MALDI-TOF mass spectrometry (MS). “Indeed, isolating the infectious microbes directly from grown liquid blood cultures using FcMBL makes them available for MALDI-TOF MS analysis much earlier,” added Super.
FcMBL is the key component of a broad-spectrum pathogen capture technology. It consists of a genetically engineered human immune protein called mannose-binding lectin (MBL) that is fused to the Fc fragment of an antibody molecule to produce the resulting FcMBL protein. In this configuration, the MBL portion of FcMBL can capture more than 100 [CHECK WITH MIKE] different microbial species with high efficiency, including virtually all of the bacterial and fungal pathogens causing sepsis. FcMBL’s Fc portion can be used to couple it to magnetic beads, allowing the captured pathogens to be quickly pulled out of patient samples and liquid blood cultures.
In the earlier stages of the project, the Wyss team provided purified bead-coupled FcMBL to the GOSH team, which had access to blood samples from pediatric patients at the hospital. At later stages, the sepsis and infectious disease company BOA Biomedical, co-founded by Super and Ingber to commercialize the Wyss Institute’s FcMBL technology, provided the FcMBL reagent and critical expertise to the project. BOA Biomedical meanwhile developed the manufacturing capabilities for FcMBL that the Food and Drug Administration (FDA) in the US and other federal health agencies require for producing therapeutic and diagnostic products.
“Sepsis is the leading killer in hospitals, and rapidly initiating the right antibiotic saves lives. Using work originally developed at the Wyss Institute, BOA Biomedical’s revolutionary FcMBL technology helps to quickly and accurately identify the pathogen causing sepsis, ushering in a new era of targeted antimicrobial therapy to help individual patients and curb society’s deadly antimicrobial resistance problem,” stated Mike McCurdy, M.D., Chief Medical Officer of BOA Biomedical.
In addition to using the gold standard two-step blood culture in combination with MALDI-TOF MS pathogen identification, the team also included the Bruker Corporation’s MBT Sepsityper® kit as a comparison. Brought to market in 2021, the MBT Sepsityper® essentially eliminates the time-consuming second microbial culture step by lysing microbial cells from the liquid culture and spinning the fragments down in a centrifuge before analyzing them by MALDI-TOF mass spectrometry analysis. Although it accelerates the overall diagnostic process, the MBT Sepsityper® methodproduces lower microbial detection rates than those obtained with the conventional culture method, which means that it may still fail to identify the infection-causing pathogen in a significant fraction of blood samples.
“Our FcMBL approach has opened up the opportunity to identify pathogenic organisms to guide treatment 24 to 48 hours earlier than would be possible using standard culture techniques. It has also enabled us to use this identification to make any ongoing culture for antibiotic sensitivities more tailored to the needs of the patient. This method isn’t tied into a specific platform or manufacturer, and thus we see clear potential for it to become a new standard processing step for clinical pathogen detection,” said Cloutman-Green.
“The FcMBL method identified 94.1% of microbial species found in clinical blood culture analysis with samples from 68 pediatric patients,” said first author Kerry Kite, who performed her graduate work with Klein and Cloutman-Green. “We were able to identify more infectious species in positive liquid blood cultures using the FcMBL method than with the MBT Sepsityper® method (25 of 25 vs 17 of 25), and this trend was even further pronounced in the case of the common fungal pathogen Candida (24 of 24 vs 9 of 24).” Candida species account for about 5% of all cases of severe sepsis and are the fourth most common pathogen isolated from patients’ bloodstreams in the United States. Not only do infections with Candida and other fungi require specific antifungal treatments, distinguishing among the various types of pathogenic fungi helps direct the appropriate antimicrobial therapy. Specifically in neonatal intensive care units, Candidainfections are a major cause of morbidity and mortality, killing as many as 40% of infants and often causing neurodevelopmental impairments in those that survive.
“By continuously adapting the powerful FcMBL pathogen capture technology to unmet and pressing diagnostic needs, such as the rapid diagnosis of sepsis in pediatric patients, we hope to profoundly alter the frequently dismal prospects of patients of all ages,” said Ingber. “Our ultimate goal is to be able to accurately and even more rapidly identify pathogens directly in small samples of blood without the need for any additional microbial cultures.” Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
The study was also authored by Sahil Loomba and Thomas Elliott at Imperial College London; Francis Yongblah, Lily Gates and Dagmar Alber at GOSH; George Downey and James Hill at BOA Biomedical; and Shanda Lightbown and Thomas Doyle at the Wyss Institute. The authors were supported in their work by the clinical microbiology staff at GOSH, as well as Erika Tranfield with MALDI-TOF MS expertise. At GOSH, critical financial help for the project from the Benecare Foundation, philanthropists Luca Albertini and Professor Pauline Barrieu, as well the Office of Vice-President (Advancement) at University College London was coordinated by Simona Santojanni. At the Wyss Institute, the study was funded by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement Number W911NF-16-C-0050, and the Wyss Institute’s technology translation engine. Additional support was provided by BOA Biomedical.
Kerry Anne Kite, Sahil Loomba, Thomas J. Elliott, Francis Yongblah, Shanda L. Lightbown, Thomas J. Doyle, Lily Gates, Dagmar Alber, George A. Downey, Michael T. McCurdy, James A. Hill, Michael Super, Donald E. Ingber, Nigel Klein, Elaine Cloutman-Green. FcMBL magnetic bead-based MALDI-TOF MS rapidly identifies paediatric blood stream infections from positive blood cultures. PLOS ONE, 2022; 17 (11): e0276777 DOI: 10.1371/journal.pone.0276777
Wyss Institute for Biologically Inspired Engineering at Harvard
Microbiome: From Research and Innovation to Market
