New research from the University of Georgia suggests that the intermittent fasting fad might actually reduce the risk of diabetes. Published in Nutrients, the review found that time-restricted eating may reduce the chances of developing Type 2 diabetes and improve overall health.
Time-restricted eating involves having regular but fewer meals, cutting out late-night snacks and not eating for 12 to 14 hours (often overnight). After a comprehensive review of published, peer-reviewed studies, the researchers found a connection between number of meals and obesity and Type 2 diabetes.
“What we’ve been taught for many decades is that we should eat three meals a day plus snacking in between,” said Krzysztof Czaja, an associate professor of biomedical sciences in UGA’s College of Veterinary Medicine. “Unfortunately, this appears to be one of the causes of obesity.” The study was co-authored by Carlee Harris, an undergraduate biology major in UGA’s Franklin College of Arts and Sciences.
The three meals and snacks style of eating prevents insulin levels from going down during the day, and, with the amount of calories and sugars Americans consume on average, that can overload the body’s insulin receptors. That leads to insulin resistance and often Type 2 diabetes.
“That’s why it’s so hard to lose body fat,” Czaja said. “We are not giving our bodies a chance to use it. Having fewer meals a day will allow these fat deposits to be used as an energy source rather than the sugar we keep consuming.”
Modern eating approach disrupts body’s biological clock
The researchers found that time-restricted eating allows the body to relax and lower insulin and glucose levels, which in turn can improve insulin resistance, brain health and glycaemic control. It can also reduce calorie intake by around 550 calories per day without the stress of calorie counting.
Previous studies have shown disruptions to sleep and meal schedules can change both the type and amount of bacteria and other microorganisms in the digestive tract. But fasting may positively alter the gut microbiome, potentially staving off inflammation and a variety of metabolic disorders.
Additionally, the review suggests time-restricted eating can help regulate hormones responsible for appetite regulation and energy levels.
Regular meal schedules, eating breakfast and decreasing meals and snacks can help guard against obesity and Type 2 diabetes, according to the publication. And all breakfasts aren’t created equal. Aim for healthy fats and protein, like eggs, and avoid the sugar-filled breakfast cereals and pastries.
Although time-restricted eating appeared to improve health, the researchers found that other types of restricted eating, such as fasting for days on end, provided few benefits.
Regular but fewer meals can stave off obesity and metabolic disorders
The modern approach of three meals plus snacks became popular decades ago, and it’s a hard pattern to break.
“But our gut-brain signalling is not designed for this type of eating,” Czaja said.
The researchers caution that eating is not a one size fits all situation. Smaller, less active people need fewer calories on average than taller athletes, for example. So for some, one meal of nutrient-rich food might be another while others may need more.
But one thing was very clear from the literature they reviewed: Fewer meals of high-quality food is a good guideline for individuals at risk of developing Type 2 diabetes and obesity.
“Also definitely avoid late-night eating,” Czaja said. “Our midnight snacks spike insulin, so instead of us going into a resting state when we sleep, our GI is working on digestion. That’s why we wake up in the morning tired – because we don’t get enough resting sleep.”
University of Turku researchers have discovered that gliomas contain increased amount of folate receptor expression relative to adjacent brain tissue. This discovery is a new and significant finding in the field, which could allow folate-based radiopharmaceuticals can be used in positron emission tomography (PET) imaging to detect folate receptors in gliomas.
This phenomenon, which is described in Frontiers in Immunology, has been observed in both experimental models and human tumour samples.
“Prior to this discovery, the presence of folate receptors and their increased presence in gliomas had not been recognised, and thus they have not yet been used for imaging nor treatment purposes,” summarises Doctoral Researcher Maxwell Miner from the Turku PET Centre at the University of Turku in Finland.
According to research group leader and InFLAMES PI Professor Anne Roivainen this presents an especially exciting target for potential future treatments.
“Our results show an average of 100-fold increase in folate-based radiopharmaceutical accumulation in glioma tissue versus that of adjacent healthy brain tissue,” says Professor Roivainen.
Urgent need for new chemotherapy treatments
Glioma brain tumours originate from the non-neuronal glial cells in the brain, which outnumber neurons in quantity. Gliomas comprise numerous subgroups, with even a high degree of morphological and receptor variability within a single cancerous lesion.
This exceptional cellular heterogeneity can make treatment difficult. There is an urgent need for new chemotherapy treatments particularly for the most malignant brain cancers as they often grow in an infiltrative web-like manner on their periphery making distinguishing the boundaries between glioma and non-glioma difficult. The researchers at the Turku PET Centre hope that this recent discovery will lead to further investigation into folate-targeted brain tumour detection and treatment.
Using parasites to treat disease may be the stuff of mediaeval medicinal horror stories, but for inflammatory bowel disease, it might actually be a worthwhile treatment. In a feasibility study published in Inflammatory Bowel Diseases, researchers from the Malaghan Institute found that hookworms were a safe and long-lasting treatment for participants with ulcerative colitis – paving the way for wider clinical studies.
For a number of years, Malaghan Institute researchers have been investigating therapeutic benefits of human hookworms for patients suffering allergic and inflammatory disease.
“This pilot study is the first controlled evidence in the use of hookworm as a therapy in ulcerative colitis,” says Malaghan Institute clinician and gastroenterologist Dr Tom Mules who led the study alongside Rutherford Clinic gastroenterologist Dr Stephen Inns. “Our study has shown this kind of therapy is well-tolerated, safe and feasible to take into a full-scale trial.”
In this pilot randomised controlled trial, patients currently in remission from ulcerative colitis were infected with a controlled dose of hookworm larvae or given placebo, and followed up over 12 months. Patients would provide regular feedback on any changes to their gut health or discomfort. Samples were collected throughout the year-long infection to test a range of scientific parameters such as gut inflammation, microbiome and immune cell composition.
“We deliberately chose to target patients with ulcerative colitis in remission,” says Dr Mules.
“We believe that the effect of hookworms may not be strong enough to push someone from an active disease state into disease remission. However, once someone is in remission hookworm could keep them there, prevent them from having disease flares and reduce the need to take medication, such as steroids, which suppresses the immune system and has adverse effects.”
Living in remission from an inflammatory disease typically means that patients experience less pain and discomfort associated with active disease. In order to stay in remission patients generally have to take daily medications to prevent flare ups. However, Dr.= Mules explains that there are significant barriers to taking daily medication, particularly when you do not have active symptoms to remind you to take pills morning and night. Importantly, not taking the medication increases the risk of having a flare. Disease flares impact quality of life, can lead to disease complications and need strong medications to bring under control.
“One of the key findings from this study was that a single dose of hookworm can reside in the body for several years, if not longer,” says Dr Mules. “This means that if hookworm is effective at preventing disease flares you can get infected and potentially no longer have to daily medicate. ‘Infect and forget’. The worms just sit there in the background and do their thing. I think that’s where the power of this therapy lies.”
The team needed to confirm safety before they could test their “infect and forget” theory in a full-scale trial.
“We did see that around the 6–8 week mark participants reported mild tummy symptoms, but those had all resolved by week 10–12,” says Dr Mules. “Otherwise, compared to the placebo group there was no significant differences in adverse events.
“The fact that these worms are well tolerated and safe to give to people with inflammatory disease is really important. One of the big safety questions was if the immune response triggered by the hookworm in the early stages of the infection could trigger a flare of ulcerative colitis. We did not see this, again highlighting that this therapy is safe in these patients.”
With no effective cure for severe inflammatory and allergic diseases the idea of using hookworms to manage harmful and aggressive symptoms is something many people have latched onto. There exists a thriving “underground” market of people self-medicating with hookworms, and significant anecdotal evidence indicating they are helpful in treating disease and managing symptoms, says Dr Mules.
“We know that people with inflammatory bowel disease, including ulcerative colitis, already use medically unsupervised hookworms to manage their symptoms and regain some semblance of quality of life, however the evidence needed to support this is lacking. The aim of this study was to provide some solid scientific groundwork, to hopefully one day make this a real, legitimate therapy to help people living with debilitating disease.”
The team now plans larger clinical trials and applying their findings to other diseases.
“The power of our study’s findings is that we can apply them to other diseases as well,” says Dr Mules. “We are in the process of deciding what the best disease target is. It could be ulcerative colitis but there are also early findings demonstrating hookworm therapy could be beneficial to a wide-range of autoimmune, allergic and metabolic diseases.
“We’re extremely grateful to the participants for taking part in this important study which will let us apply hookworm therapy where it will have the biggest impact.”
While grandmothers today have a popular image of spoiling their grandchildren with treats, in premodern times they also acted as healthcare providers. To find out more, University of Turku researchers looked at historical data on childhood mortality from infectious diseases in the 18th and 19th century in Finland. The study, which is published in the journal Proceedings of the Royal Society B, found that grandmothers decreased all-cause and cause-specific mortality of children.
In historical and in several contemporary societies, children with living grandmothers are more likely to survive into adulthood, but the mechanism behind this effect remains poorly known.
As childhood infections have been a leading cause of death in children under the age of 5 years, the researchers aimed to investigate whether the effect of grandmothers on childhood survival was related to providing knowledge in childcare, particularly during critical times such as epidemics. One way for grandmothers to do so could be by encouraging vaccine uptake or earlier vaccination against childhood infections, as has been observed in some contemporary populations.
Researchers first studied the effects of grandmothers on children’s cause-specific mortality, using historical records of five causes of death: smallpox, measles, pulmonary infections, diarrhoeal deaths, and accidents. The large multigenerational dataset of pre-industrial Finnish families included 9705 individuals from 12 parishes across Finland, where the survival of individuals until the of age 15 years was monitored from 1761 to 1900. In the second part of the study, the researchers determined whether increased survival against the childhood infection smallpox was mediated by vaccination. To this end, they used 1594 vaccination records from two rural parishes and matched them to their individual family histories.
The results show that grandmothers decreased all-cause mortality, an effect which was mediated through improved survival from smallpox, pulmonary and diarrhoeal infections, but not from measles or accidents. However, the researchers found no evidence of increased or earlier vaccination between children with or without grandmothers.
“Our results show that the grandmother’s presence protected against some childhood infections, which could indicate that in historical Finnish society, the assistance provided by grandmothers in childcare was likely an important factor in ensuring the survival of children,” says study lead author, Doctoral Researcher Susanna Ukonaho.
Grandmothers in contemporary societies
Although grandmother care provided health benefits in many historical societies, these benefits may no longer be relevant in contemporary societies. The progress in healthcare during the 20th century especially in high-income countries likely decreased the role of grandmothers. However, some studies indicate that grandmothers improve childhood survival in several contemporary middle- and low-income countries.
“The type of benefits that grandmothers provide may vary depending on cultural contexts and individual circumstances. Even though in many societies grandmothers are no longer essential for childhood survival, their efforts in childcare remain valuable for the well-being of the whole family,” says Ukonaho.
South African scientists – notably, the team headed by Professor Tulio de Oliveira – were thrown into the global spotlight through their pivotal role in detecting and monitoring the emergence of new variants of SARS-CoV-2 – the Beta variant in 2020 and Omicron in 2021. De Oliveira is now at the University of Stellenbosch, but for much of the pandemic headed the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP).
The country’s advanced genomic sequencing capabilities and proactive surveillance efforts allowed for the early identification of the variants and the discoveries played a crucial role in alerting the global scientific community to the potential for viral mutations and the need for enhanced monitoring.
Now, scientists worldwide believe it is critical to continue investing in genomics to support disease control in public health in South Africa and the broader continent.
What is genomics?
The World Health Organization (WHO) defines genomic surveillance as “the process of constantly monitoring pathogens and analysing their genetic similarities and differences”. It is done through a method known as whole genome sequencing, which determines the entire genetic makeup of specific organisms or cell types. This method is also able to detect changes in areas of genomes, which can help scientists to establish how specific diseases form. The results of genomic sequencing can also be used in diagnosing and treating diseases.
Genomic sequencing enables scientists to read the DNA and RNA of pathogens and understand what they are and how they spread between people – and to develop vaccines and other measures to deal with them.
The US Centers for Disease Control (CDC) explains, “All organisms (bacteria, vegetable, mammal) have a unique genetic code, or genome that is composed of nucleotide bases (A, T, C, and G). If you know the sequence of the bases in an organism, you have identified its unique DNA fingerprint or pattern. Determining the order of bases is called sequencing. Whole genome sequencing is a laboratory procedure that determines the order of bases in the genome of an organism in one process.
“Scientists conduct whole genome sequencing by following these four main steps:
DNA shearing: Scientists begin by using molecular scissors to cut the DNA, which is composed of millions of bases (A’s, C’s, T’s, and G’s), into pieces that are small enough for the sequencing machine to read.
DNA barcoding: Scientists add small pieces of DNA tags, or bar codes, to identify which piece of sheared DNA belongs to which bacteria. This is similar to how a bar code identifies a product at a grocery store.
DNA sequencing: The bar-coded DNA from multiple bacteria is combined and put in a DNA sequencer. The sequencer identifies the A’s, C’s, T’s, and G’s, or bases, that make up each bacterial sequence. The sequencer uses the bar code to keep track of which bases belong to which bacteria.
Data analysis: Scientists use computer analysis tools to compare sequences from multiple bacteria and identify differences. The number of differences can tell the scientists how closely related the bacteria are, and how likely it is that they are part of the same outbreak…”
Time to expand
At a recent conference held at Stellenbosch University’s new state-of-the-art Biomedical Medical Research Institute, de Oliveira stressed that African and other experts should now build on their success in COVID-19 genomics to expand to other pathogens such as influenza, H5N1, and climate-amplified pathogens.
John Sillitoe, the Director of the Genomic Surveillance Unit at the Wellcome Sanger Institute in the United Kingdom, agreed.
“It is important now to focus on endemic diseases so we can improve our understanding and control of endemic diseases. We should also be looking at TB, particularly with the increased prevalence in drug resistance and reduced response to drugs. For other African countries, malaria should be a key focus area. We know that drug resistance now is spreading into Africa from South East Asia and understanding the right combination of drugs to use is something that is easily identifiable through genomic surveillance.”
But surveillance is also about being ready for the next pandemic.
“There’s that classic line that, ‘diseases take no notice of national borders’,” Sillitoe said in an interview. “So, it is really important that we can get as wide a picture of surveillance as possible to identify something new emerging as soon as possible.”
Marco Salemi, Professor of Experimental Pathology at the Department of Pathology, Immunology, and Laboratory Medicine at the University of Florida College of Medicine, said Africa and the world need to be “proactive, rather than reactive” in the battle against future epidemics. He said the world is currently focused on monitoring the COVID-19 pandemic. “But we forget this is this huge reservoir of pathogens out there which we know so little about and which can become more and more of a threat, especially because of climate change – so we need to understand more about all these pathogens in the wild, in animals, and their potential to jump to humans, especially with the rate of globalisation on the planet … Events of zoonotic transmissions will become more and more frequent. We need to face it.”
Building capacity
De Oliveira is of the view that Africa could, in the next few years, potentially, “leapfrog over the rest of the world” in genomic surveillance, thanks to its success in COVID-19 genomics and its experience in using genomics to monitor other pathogens over the past 20 years.
We won’t be starting from scratch.
The use of genomics in infectious diseases started in the mid-eighties during the HIV epidemic, when scientists realised HIV was a complex virus that existed in many different sub-types. Scientists around the world started using genomic tools to sequence the HIV virus, track its origin, and trace the way the virus disseminated.
Genomics has, however, changed dramatically since the 1980s.
“There have been many attempts… to use genomics for public health purposes, but the key factor that was always missing was the ability to generate DNA sequencing in real-time,” said Salemi. “Real-time means there is an epidemic, with cases happening today – and we need to generate sequences within one or two days and then to analyse the genomic data and then to have actionable information that can be immediately transmitted to the public health authorities so that they can act within a few days.”
“Now the technological and computational limitations of the past few years have been overcome, and, as was clearly shown during the COVID-19 pandemic, we have machines that can generate literally thousands of sequences, like coronavirus sequences, in less than one day, or even within a few hours. At the same time, we have high-performance computer clusters, and super calculators that are capable of analysing this data in a very short time,” he said.
These technical advances would, of course, be of little value without people to use them and develop them further.
“Investment has been made on the continent in infectious disease surveillance and genomics surveillance specifically, and so we have lots of experts on the continent who know a lot about infectious diseases and how viruses work, and why it’s important to look at the genomics to trace when there is going to be a new outbreak,” says Professor Zané Lombard, Principal Medical Scientist in the Division of Human Genetics at the University of the Witwatersrand. “South Africa’s role during COVID-19 showcased what can happen quickly and effectively for public health interventions if you have the right experts with the right platform and expertise and infrastructure in place to do that kind of surveillance.”
De Oliveira and his team have worked closely with the Africa Centres for Disease Control and Prevention (Africa CDC) to scale genomic surveillance on the continent and have actively collaborated with other African countries to share expertise, resources, and genetic data in a bid to foster a continent-wide approach to genomic surveillance.
They have also helped set up large genomics facilities in Zimbabwe, Mozambique, and Botswana.
The Africa CDC, through its Pathogen Genomics Initiative (Africa PGI), has, for the past few years, been building a continent-wide genomic disease surveillance network. In 2019, when the PGI started its work, only seven of the African Union’s 55 member states had public health institutions with the equipment and staff to do genetic sequencing. Today, 31 African nations are able to do genetic sequencing for surveillance of COVID, malaria, cholera, Ebola, and other diseases.
De Oliveira said the continent’s experience in genomic surveillance of pathogens in Africa evolved to “unheard-of” levels during COVID. “We’ve been trying to advance genomic surveillance in Africa for the past two decades, and when the pandemic came, we had the right expertise to deal with viruses and respiratory pathogens such as tuberculosis, so we were able to pivot for SARS-CoV-2. In the end, South Africa and Africa became an example to follow for the whole world.
“All the investments we have made in genomic surveillance for COVID can now be leveraged and advanced to other areas of genomics in Africa… including for rare diseases, for cancer diagnostics, and human genomics. Finally, we have the tools and the equipment, as well as the support, to do advanced genomics in Africa, as we have dreamt of doing for the last twenty years.”
What it means in practical terms
Asked what it means, practically, to build capacity for genomics research, Lombard said one aspect is the establishment of strong laboratories. “Historically, if infrastructure was not available locally, researchers would partner with international labs and send their samples to have their sequencing done there. The problem with that was that expertise in using [that] technique was not being built locally,” she said. “It is really important to train the right people who know how to do the laboratory experiments but also to interpret the data correctly.
“It’s not only about building the infrastructure in the labs but also about training the individuals and making sure there are job opportunities locally for them,” she said.
Turning to the machines used in genomics, Lombard said, “The most popular machine these days is called a next-generation sequencer. These can read the whole DNA sequence of a virus.”
Salemi added, “Some of these sequencers are very large and some are even little portable boxes. Some can sequence thousands of samples at a time, while others are capable of sequencing a few dozen samples at a time. The samples, depending on the virus (or pathogen) being tested for, are taken from blood samples, nasal swabs, or sputum from patients, from faeces, urine, or from the skin.
“The BMRI (at Stellenbosch University) – which has the largest sample storage capacity in the southern hemisphere – can store five million samples at minus 80 degrees. If someone wants to build a lab that includes top-of-the-line computational capacity, it will cost anything from $40 million (over 700 million), but to start a small operation to do a few hundred sequences of a virus every week, $100 000 to $200 000 (roughly R17 million to R34 million) is enough, which has been done in many different African countries during the pandemic.”
Training is key
While all the scientists interviewed agreed that laboratories are important in building capacity for genomics research, they stressed that what is really needed is to train more individuals.
“More people need to be trained in genomics but also in bioinformatics, which is a really important component of this work. The technology component is becoming very smart and automated, but the data being generated is becoming more and more complex, with bigger data sets. Dealing with these,” Lombard said, “requires special data analysis skills and bioinformatics skills. The field of bioinformatics will need investment so that we can deal with the deluge of data that will come out.”
She said South African and other African universities are taking this skills need seriously, with many initiatives to offer undergraduate and post-graduate training programmes in these areas.
Salami agreed. “The most important part of building capacity is the human training. I find it naïve and sad when I hear politicians talking about building top-of-the-line laboratories, when, what they really need to do is to start building human capacity. Africa is an amazing reservoir (from which to build these skills) because 50 percent of the continent [are] people who are less than 30 years old. There are about 27 excellent laboratories all over Africa. We need to start creating a strong next generation of scientists.”
In support of this, de Oliveira is trying to raise 100 million dollars to implement real-time genomic research to enable the African continent to respond to new epidemics.
He said during COVID, the Network for Genomics Surveillance was founded and funded by the Department of Science and Innovation and the South African Medical Research Council (SAMRC). This funding was until 2021.
The Centre for Epidemic Response and Innovation, which is led by de Oliveira and forms part of the BMRI, is funded by the Africa CDC, the WHO, the Rockefeller Foundation, and the Elma Foundation. These funders support the work in South Africa and in other African countries, as well as the SA government. The BMRI was mostly funded by Stellenbosch University to the effect of R900 million, while the Department of Higher Education provided about R300 million. CERI occupies one floor of the BMRI.
In de Oliveira’s words, “This truly is the genome era for Africa.”
