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5th March 2024
The lockdowns imposed during the Covid-19 pandemic positively impacted the gut microbiome and subsequent allergy development of babies born during this time, a new study has revealed.
Researchers working in Ireland found significant differences in the gut microbiome development of babies born during lockdown periods compared to pre-pandemic babies, including lower than expected rates of allergenic conditions.
The findings, published in the journal Allergy, highlighted how environmental exposures and dietary components significantly impacted microbiota community assembly.
And they were the first to demonstrate gut health benefits arising from the unique lockdown environment, including lower rates of infection and consequent antibiotic use and increased duration of breastfeeding.
The researchers from the Royal College of Surgeons in Ireland (RCSI), Children’s Health Ireland and APC Microbiome Ireland at University College Cork collected faecal samples from 351 babies born during the first three months of the pandemic. The samples were collected at six months (n = 351) then at 12 (n = 343) using 16S sequencing.
Skin prick testing (SPT) was performed at 12 (n = 343) and 24 (n = 320) months of age, accompanied by atopic dermatitis and food allergy assessments.
In infants with atopic dermatitis, a Scoring Atopic Dermatitis (ScorAD) was calculated at 12 and 24 months and a total and objective ScorAD recorded. SPT was completed for the three most common food allergens (peanut, egg and milk) and aeroallergens (house dust mite, grass pollen and cat dander) in all infants.
Online questionnaires were used to gather epidemiological information about the babies’ diet, home environment, health and healthcare utilisation and allergic diseases, including suspected adverse food reactions and atopic dermatitis.
The pandemic-born babies were part of the CORAL (Impact of CoronaVirus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown) project, and the results were compared with samples from pre-pandemic cohorts of babies.
Professor Liam O’Mahony, from the University of Cork and principal investigator at APC, said: ‘We took the opportunity to study gut microbiome development in infants raised during the early Covid-19 era when strict social distancing restrictions were in place, as the complexity of early life exposures was reduced and this facilitated a more accurate identification of the key early life exposures.
‘Prior to this study, it has been difficult to fully determine the relative contribution of these multiple environmental exposures and dietary factors on early life microbiome development.’
Significant differences existed in the gut microbiomes of the two cohorts. Pandemic-born babies showed a higher relative abundance of bifidobacteria at both six and 12 months, which was associated with a reduced likelihood of atopic dermatitis and positive SPT results.
Infants with elevated Bifidobacterium levels at six months of age typically exhibited fewer allergic symptoms or a lower risk of developing allergic diseases than those with lower levels of this bacteria.
The increase in bifidobacteria was linked to reduced external exposure, an increase in breastfeeding and a decrease in antibiotics during lockdown.
Social distancing was associated with delayed acquisition of horizontally transmitted spore-forming bacteria. Bacteria such as the environmentally transmitted Clostridia were found to have lower concentrations at both six and 12 months in the pandemic cohort compared with the pre-pandemic babies, correlating with the microbial exposure index.
Levels of atopic dermatitis observed in the study were not higher than expected levels. Specifically, at 12 months of age, atopic dermatitis was observed in 24.8% of participants (n=343), and at 24 months, it was observed in 19.5% (n=320).
Levels of food allergen and airborne sensitisation were also within the expected range for this age group, with SPT positivity at 7.4% at 12 months and 12.0% at 24 months.
The prevalence of allergen sensitisation, food allergy, and atopic dermatitis did not increase over pre-pandemic levels, suggesting the lockdown period did not lead to a higher incidence of allergic conditions.
Joint senior author of the study Professor Jonathan Hourihane and head of paediatrics at RCSI, added: ‘This study offers a new perspective on the impact of social isolation in early life on the gut microbiome.
‘Notably, the lower allergy rates among newborns during the lockdown could highlight the impact of lifestyle and environmental factors, such as frequent antibiotic use, on the rise of allergic diseases.’
The researchers hope to re-examine the children born during the pandemic when they are five years old to investigate whether there are longer-term health benefits arising from the early differences seen in the gut microbiome.
In August 2023, researchers found that delays in gut microbiome maturation in young children were uniformly associated with distinct allergic diagnoses at five years of age.
20th October 2023
The potential for detection of colorectal cancer based on an analysis of the variability in a patient‘s gut microbiome has been highlighted in a study presented at United European Gastroenterology (UEG) Week.
The findings come from the Dutch microbiome project, which is a large-scale studying involving 8,208 participants. Researchers analysed the gut microbiome of those who developed pre-cancerous colorectal lesions before faecal sampling between 2000 and 2015, in addition to those who developed such lesions following sampling between 2015 and 2022.
They then compared the results with samples taken from individuals with a normal colonoscopy, as well as exploring the range of bacterial species present and their function within the gut by reconstructing their genomes from metagenomic data.
The team identified that when compared to those who had a normal colonoscopy, individuals who developed colonic lesions after faecal sampling displayed a greater diversity in their gut microbiome. In addition, the composition and function of the microbes differed in those with pre-existing or future lesions based on the type of lesion.
In terms of the specific organisms, researchers identified that those from the family of Lachnospiraceae and the genera Roseburia and Eubacterium were linked with the future development of lesions.
Significant variation in the gut microbiome of individuals who developed pre-cancerous colorectal lesions offers another potential avenue to explore to enhance the detection and prevention of colorectal cancer.
Commenting on the findings, study lead, Dr Ranko Gacesa, postdoctoral researcher at the University Medical Center Groningen in the Netherlands, said: ‘While we didn’t investigate mechanisms in this study, it is known from previous research that some of the bacterial species identified may have properties that could contribute to the development of colorectal lesions.
‘A bacterium called Bacteroides fragilis, for example, is known to produce a toxin that can lead to chronic low-grade inflammation in the gut. Prolonged inflammation is believed to be potentially genotoxic and carcinogenic, meaning it may cause genetic damage and promote cancer.’
In a discussion of the potential implications of the study findings, Dr Gacesa added: ‘The connection between the gut microbiome and pre-cancerous lesions has been underexplored, leaving uncertainty about whether gut bacteria can predict the future onset of colorectal cancer.
‘Our findings suggest that the microbiome could act as a valuable tool to improve existing tests, advancing early detection methods for pre-cancerous lesions and colorectal cancer.’
According to the World Health Organization, colorectal cancer is the third most common cancer and there were nearly two million cases and almost one million deaths in 2020, with a spike in diagnoses of the cancer at an advanced stage during the pandemic.
In addition, an increasing number of studies reveal how the progression of colorectal cancer is related to gut microbiome composition. In fact, the published literature related to the development of colorectal cancer has demonstrated that many bacteria affect tumour development and growth. It is also clear that gut microbiome can modulate the efficacy of conventional chemotherapy, through regulating cytotoxicity by participating in the metabolic process of anti-cancer drugs.
4th October 2023
Changes in the gut microbiome are known to affect the response to immunotherapy in patients with melanoma, but whether it is therefore possible that modulating gut dysbiosis could halt disease progression remains unclear. Clinical writer Rod Tucker investigates.
Cutaneous melanoma is the 17th most common cancer worldwide and the last 40 years has seen a steady increase in the number of cases, with a more than eight-fold increase from 1985 to 2018.
A further cause for concern is that melanoma has invasive metastatic growth patterns and is one of the most aggressive types of skin cancer.
Fortunately, in recent years, the introduction of immunotherapies has marked a major advancement in the treatment of melanoma. As a result, immunotherapy is now considered to be a promising new approach for the treatment of metastatic melanoma.
Curiously, one factor that appears to influence the outcome of immunotherapy in patients with melanoma is their gut microbiome.
This vast microbial community resides symbiotically within the human gut, contributing to homeostasis and regulating immune function. The terms microbiota and microbiome are often used interchangeably, although, strictly speaking, the ‘microbiome’ refers to a collection of genomes from all of the microorganisms, the microbial structural elements and metabolites.
The fact that the gut microbiome influences a patient’s response to chemotherapy, was first revealed in a 2013 study using mouse models. Researchers observed that among either antibiotic-treated or germ-free mice, tumour-infiltrating myeloid-derived cells responded poorly to chemotherapy.
Later work confirmed this relationship. Again, using mouse melanoma models, it was shown that supplementing with oral bifidobacterium, improved tumour control to the same degree as programmed cell death protein 1 ligand 1-specific antibody therapy.
This effect was also observed in humans in a 2017 study. Researchers examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 (anti-PD-1) immunotherapy. They were able to show via immune profiling, that there was an enhanced systemic and anti-tumour immunity in responding patients who had a favourable gut microbiome.
In fact, it became clear that there was a significant association between commensal microbial composition and clinical response in patients with metastatic melanoma.
Taken together, these findings made clear that a patient’s gut microbiome was able to influence their response to immune checkpoint inhibitor therapy. But the observations only raised more questions.
For example, was the diversity of the gut microbiome linked to the development of melanoma? Furthermore, did melanoma progress because of a gut dysbiosis? And, if the two were linked, could this information be used either prognostically or even therapeutically?
Some answers to these emerging questions came from a recent study. Researchers were interested in exploring if there were any differences in the gut microbiome of patients with melanoma compared to healthy controls and between those at an early and late stage of the cancer.
The study, which was published in the journal JAMA Dermatology, characterised and compared gut microbiota profiles between healthy volunteers and patients with melanoma either at an early (stages 0 to II) or at a late stage (III to IV) of their disease.
A total of 228 participants were enrolled, of whom 49 were healthy controls, 38 had early stage disease and 141 had with late stage disease.
When comparing the microbiomes of individuals with melanoma against healthy controls, there were significant differences in alpha diversity with a higher number of unique species present among the healthy control group (p = 0.06).
But when looking at the beta diversity, which measures the differences between the two groups, healthy control samples formed distinct or distant communities as compared with patients who had melanoma (p <0.001). In fact, healthy controls had a greater abundance of the bacterial phyla Actinomycetota and Firmicutes.
One interesting observation was the higher level of species from the bacterial genus Fusobacterium, was significantly more abundant in the melanoma group compared to controls. This species has been found to be present at higher levels in patients with colorectal cancer and is associated with a shorter survival. Nevertheless, in the current study, while higher in melanoma patients, the difference was no longer significant after statistical adjustment.
When researchers compared the microbiome of those with early and late-stage melanoma, they found both a significantly higher alpha and beta diversity in those in the earliest stage of their cancer. In other words, it seems that melanoma progression is associated with a reduction in the diversity of the gut microbiome.
So, if microbiome diversity reduces as malignant melanoma progresses, could improving the alpha diversity prevent the subsequent development of the cancer?
It is an intriguing thought that simply by enhancing the range of microorganisms within the gut, it could be possible to halt melanoma progression. And this idea may not be as far fetched as it might sound.
There is emerging evidence to suggest that improving the gut microbiome, might represent an effective adjunct to immunotherapy. For example, in a study from 2021, researchers showed that the use of faecal microbiota transplantation in 10 patients with anti-PD-1-refractory metastatic melanoma elicited a clinical responses in three patients: two achieved a partial response and one complete response.
More recently, in a second trial, researchers found that faecal microbiota transplantation from healthy donors to 20 patients with advanced melanoma who were in receipt of anti-PD-1 therapy, gave rise to an objective response rate of 65% and a complete response rate of 4%.
While faecal transplantation may not appeal to many, an alternative approach could be to increase alpha diversity with probiotics. In a case report of two patients with metastatic melanoma whose cancer progressed on immune checkpoint inhibitors, the combination of the Camu Camu probiotic with immunotherapy produced a both a complete and near complete response to therapy.
There is no doubt that the evidence to date has been able to shine a light on the importance of the gut microbiome in shaping a patient’s response to immunotherapy. Unfortunately, so far, research has only been able to demonstrates an association rather than causality. For instance, it remains unclear as to whether the reduced alpha diversity is actually the cause or merely a consequence, of melanoma progression. Research is also be hampered by the absence of what constitutes an ’optimal’ gut microbiome composition.
Despite these limitations, in the current era of precision medicine, a strategy that involves modulation therapy to improve the alpha diversity of the gut microbiome could play an important role in the future management of melanoma.
4th September 2023
Delays in gut microbiome maturation in young children are uniformly associated with distinct allergic diagnoses at five years of age, according to the findings of a study by Canadian researchers.
The study, which was published in the journal Nature Communications, revealed how specific gut microbiome features and early life influences are associated with children developing any of four common allergies: atopic eczema, asthma, food allergy and/or allergic rhinitis.
It is possible, therefore, that these findings could lead to methods for predicting whether a child would develop an allergic disease. They could also form the foundation of strategies to prevent them from developing, especially given that food allergies in particular continue to be a major source of life-threatening reactions in children.
Courtney Hoskinson, PhD candidate at the University of British Columbia (UBC) and the study‘s lead author said: ‘Typically, our bodies tolerate the millions of bacteria living in our guts because they do so many good things for our health. Some of the ways we tolerate them are by keeping a strong barrier between them and our immune cells and by limiting inflammatory signals that would call those immune cells into action.‘
‘We found a common breakdown in these mechanisms in babies prior to the development of allergies.‘
In the study, researchers evaluated the four clinically distinct allergic diseases diagnosed at five years of age in the large, deeply characterised CHILD cohort study. The team adopted a multi-omics approach to profile infant stool collected at study visits scheduled for ages three months and one year.
The study used a deeply phenotyped cohort of 1,115 children. A total of 523 participants could be defined as a ‘healthy‘ control group in that they did not develop allergic sensitisation at any time in their life up to five years of age.
Some 592 children had been diagnosed by an expert physician at the five-year scheduled visit with one or more allergic disorders: atopic eczema (n = 367), asthma (n = 165), food allergy (n = 136) and allergic rhinitis (n = 187). There were gut microbiome features uniformly associated with these allergic diagnoses at five years of age.
When evaluating the association between early-life factors and a diagnosis of allergic disease at age five, male sex, a history of either maternal of paternal atopy and antibiotic usage before age one were all significantly linked with an increased risk of developing an allergic disease.
In contrast, breastfeeding up to age six months and self-identifying as Caucasian were negatively associated with an allergy diagnosis.
Dr Stuart Turvey, professor in the department of pediatrics at UBC, investigator at British Columbia Children‘s Hospital Research Institute and co-senior author on the study, added: ‘There are a lot of potential insights from this robust analysis. From these data we can see that factors such as antibiotic usage in the first year of life are more likely to result in later allergic disorders, while breastfeeding for the first six months is protective. This was universal to all the allergic disorders we studied.
‘Developing therapies that change these interactions during infancy may therefore prevent the development of all sorts of allergic diseases in childhood, which often last a lifetime.‘
8th August 2023
Irregular sleep patterns, caused by ‘social jetlag’ – the shift in a person’s internal body clock when sleeping patterns change between workdays and free days – are associated with harmful gut bacteria and adverse health outcomes, according to a new study.
Undertaken by King’s College London (KCL) and published in the European Journal of Nutrition, the study was designed to explore the relationship between social jetlag and gut microbial composition, diet and cardiometabolic health.
It found that social jetlag is associated with unfavourable diet quality, including a higher intake of potatoes and sugar-sweetened beverages and lower intakes of fruits and nuts, together with slightly higher markers of inflammation, compared to those without social jetlag.
The researchers used information from the ZOE PREDICT 1 study, which includes data from 1,002 monozygotic, dizygotic and non-twin healthy UK individuals aged 18-65 years.
The team assessed demographic, diet, cardiometabolic, stool metagenomics and postprandial metabolic measures. Sleep patterns were self-reported and used to calculate social jetlag. This was deemed to be a 90-minute difference in the timing of the midpoint of sleep – the halfway point between when a person goes to sleep and when they wake up – on weekdays versus weekend days.
The team also collected blood samples following the consumption of a standardised meal consisting of two high-fat muffins and a milkshake.
A total of 934 individuals were included in the analysis and 145 were defined as having social jetlag and the others had a routine sleep schedule. All participants were healthy and lean, and slept for over seven hours a night throughout the week.
In an analysis of their gut microbiomes, three out of six microbiota species linked to ‘unfavourable’ health outcomes were more abundant in the social jet lag group. These microbes are associated with poor diet quality and are indicators of obesity and cardiometabolic health, and create markers in the blood related to higher levels of inflammation.
Senior author for the study Wendy Hall, said: ‘We know that major disruptions in sleep, such as shift work, can have a profound impact on your health. This is the first study to show that even small differences in sleep timings across the week seems to be linked to differences in gut bacterial species.
‘Some of these associations were linked to dietary differences, but our data also indicates that other, as yet unknown, factors may be involved. We need intervention trials to find out whether improving sleep time consistency can lead to beneficial changes in the gut microbiome and related health outcomes.‘
The gut microbiome refers to the community of bacterial species within the intestines and plays an important role in the overall health of the host. In fact, the microbiome can be easily disturbed, for instance after taking antibiotics, although taking a probiotic yogurt appears to restore the antibiotic-induced disturbance.
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