Pandemic policies may have led to changes in infant gut microbiomes.

Although heavily flawed, a study from August provides the first look into how hygiene and lockdown practices may have altered microbiome diversity.

Edit: I incorrectly wrote “oligonucleotide” when referring to SNPs below. The correct term nucleotide was swapped in instead.

There’s been growing concern that the pandemic, through lockdowns, constant cleaning, lack of social gatherings, and poor diet, may have disrupted our microbiome.

This is made worse as growing evidence notes the significance in having a robust, diverse microbiome in overall health.

This is made worse for infants, whose early biodiversity may serve as a predictor for autoimmune disease later in life.

So it would be rather alarming for a study to suggest that the pandemic years may have been a detriment to infant microbiomes.

In mid-August a study published in Nature¹ appeared to provide insights into just that.

This study in particular was designed in order to address whether the pandemic years may have attributed to changes within the microbiome:

Due to widespread reductions in social activity outside the home, increased hand hygiene, and changes in patterns of family interactions brought on by COVID-19 public health directives, we hypothesized that samples collected after the start of the pandemic would have significantly lower alpha diversity than pre-pandemic samples.

The study looked at microbial diversity in stool samples of 12-month old infants from December 2018 up until December 2019 during the pre-pandemic period (n=34) and compared them to infants from the first year of the pandemic (n=20), with pandemic sample collection ending December 2020 .

Figure 1. A timeline of data collection for both pre-pandemic and pandemic stool samples.

Families were recruited from New York, and so the microbiome makeup of these infants are likely to be different from infants in suburban/rural environments. Families were also provided a survey asking for demographic data, caregiver mental status, infant diet and lifestyle (i.e. number of siblings, pets in household, etc.), as well as route of delivery of the infants. Unfortunately, the survey doesn’t appear to include any questions on hygiene practices in the home, and so given this uncertainty bear in mind that changes in hygiene practices during pandemic periods are likely to be assumed rather than verified.

When comparing survey data the only feature argued to meet statistical significance was the increase in fat consumption in pandemic infants relative to pre-pandemic infants. Although more pandemic mothers were breastfeeding at the time of stool sample collection relative to pre-pandemic mothers, the exact source of the higher fat diet isn’t described.

When looking at alpha diversity of pandemic infants relative to pre-pandemic infants, there appeared to be far less diversity in pandemic infant microbiomes. That is, fewer species were noted within the stools of pandemic infants relative to pre-pandemic infants. Note that alpha diversity refers to the enrichment and diversity of microbes within a given environment. In this case, the “environment” would be the gut of the infants.

The authors note that this difference is shown with a Chao1 analysis whereas a Shannon diversity analysis didn’t show statistically significant differences in gut population between the two groups.

Note that these two tests measure diversity differently, with a Chao test examining the actual species richness within a given sample. Shannon diversity, on the other hand, is more a measure of statistical probability, in which it examines the uncertainty in identifying a species from a sample selected at random (this appears to be done by comparing number of single nucleotide polymorphisms within a sample and the rate of selecting for these SNPs).²

Figure 2. When comparing species richness there was a significant different in stool richness in the pre-pandemic group relative to the pandemic group.

Note that greater species richness may not suggest a better microbiome, as unless these species are characterized we have to consider that some of these are symbiotic/commensal while others may be pathogenic. That being said, the large variation at least leaves open the question of why such a difference is being seen.

When comparing beta diversity the researchers also noted more homogeneity among pandemic infants relative to pre-pandemic infants. Beta diversity is step above alpha diversity ecology-wise, as beta diversity takes into account individual alpha diversities and compares their phylogenetic broadness. In this case, beta diversity measures, as conducted by UniFrac³ analysis, examines how much microbiome diversity exists among pandemic infants and compares that to microbiome diversity among pre-pandemic infants.

Figure 5. Beta diversity between pandemic groups.

Again, much of this statistical analysis is above my head, but the gist is that the less clustered the data points, and thus the wider/larger the circle, the more diversity there is in stool microbial species. Therefore, the more narrow oval shape of pandemic infant samples suggest that the microbial species within these stool samples are likely to be very similar, suggesting more homogeneity and less diversity.

Researchers also looked at differences in taxonomy richness of samples, noting that pre-pandemic infants showed higher levels of bacteria from the family Pasteurellaceae. More specifically, pre-pandemic infants had a higher level of bacteria from the Haemophilus genus (which is part of the Pasteurellaceae family). Bacteria from the Pasteurellaceae family are usually found within the mucosal membranes of mammals, including most cats and dogs. Of note, some bacteria from the Haemophilus genus, most notably Haemophilus Influenzae⁴, are the primary culprit in bacterial upper respiratory infections in children, and may cause bacterial pneumonia and meningitis. Thus, the presence of these bacteria among pre-pandemic infants may suggest exposure to pathogenic bacteria to some degree, or even possibly exposure to these bacteria by way of pets.

The researchers suggest that this difference may be due to hygiene practices given that bacteria from the Haemophilus genus are very sensitive to cleaning products, and so the lack of these bacteria in pandemic infant stools by indirectly infer greater use of disinfectant products during the pandemic:

In addition to differences in community-level taxonomic diversity across pandemic groups, we also found several differences on the individual taxa level: lower abundance of taxa from the Pasteurellaceae family and the Haemophilus genus within Pasteurellaceae among infants sampled during the pandemic relative to before the pandemic. Lower Haemophilus abundance has also been associated with more frequent use of cleaning/disinfectant products in infants and young children^4,35, though Pasteurellaceae and Haemophilus abundance was found to be higher in infants cared for at home compared to those in childcare^8,36, and those in childcare are presumably exposed to a larger number of same-age peer children as well as more stringent cleaning protocols. Taken together, our findings in combination with those from prior studies suggest that the lower abundance of Pasteurellaceae and Haemophilus observed in infants sampled during compared to before the pandemic may be due to more frequent cleaning during the early waves of the pandemic, rather than differences in social contact patterns.

That being said, note that these differences are due to 5 pre-pandemic samples in particular, and so it might be a bit of a stretch to infer that these differences are due to cleaning practices as most pre-pandemic samples seem to be comparable to pandemic samples. It would be worth considering whether infants who showed higher rates of Haemophilus counts lived in households with more pets relative to the other pre-pandemic infants, as well as the pandemic infants. There was a higher percentage of pandemic infants living with pets, although the number of pets isn’t described within the survey. This just leaves a question of why some of these infants showed higher levels of Haemophilus.

Figure 7. Abundance of Haemophilus taxa between pre-pandemic and pandemic infants. Although the researchers argue that this difference is significant, the 5 outlier samples within the pre-pandemic group warrant scrutiny, as these appear to be the main drivers in this difference.

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Overall, this study leaves quite a bit to be desired. Given that several of these bacteria species were never characterized it doesn’t tell us whether many beneficial bacteria were depleted in pandemic infants. The comment on higher fat intake among pandemic infants without describing the sources of this higher fat intake means that there is likely to be missing data on changes in dietary habits during the pandemic. Also, note that stool sample collection occurred at various timepoints, including during the pandemic. However, the researchers do comment that there doesn’t appear to be differences in richness of stool samples taken at different timepoints in 2020, which they suggest may be due to a loss of diversity right at the onset of the pandemic when everyone became more vigilante in their cleanliness. However, this would be a supposition given that this variable wasn’t measured.

Nonetheless, this study serves as a stepping stone in a broader, more robust investigation into the effects that pandemic measures may have had on our microbiomes. This is made even more important given the fact that microbiome diversity during the early stages of life may influence health outcomes during the adolescence and adulthood. This would raise a question of whether the lockdowns and constant cleaning may influence autoimmune disease and allergies in children growing up during this time period. It may also partially explain the supposed anecdotes of children constantly getting sick as soon as everything opened up.

The researchers conclude their study with the following:

It is rare to have a natural experiment, such as that afforded by the dramatic environmental changes that occurred when the COVID-19 pandemic began, in which to examine environmental influences on the early life gut microbiome. Overall, evidence from this study suggests that pandemic-related disruptions to infants’ environments had an impact on their gut microbiomes, with lower alpha diversity, differences in beta diversity, and lower abundance of several taxa seen in infants sampled during the first year of the pandemic compared to before the pandemic. Further research is needed to understand if differences in gut microbiome composition have persisted for these children, how pandemic disruptions may have influenced the gut microbiome of children at different developmental stages, and the long-term implications of these microbiome differences for children’s health-related outcomes. Results can inform our scientific understanding of microbiome plasticity to changing environmental conditions and contribute to a growing body of research on child development during the pandemic.

We’ll need to see what other insights come to light with additional research, but all of this just adds further evidence that all of the public health policies from the pandemic may have caused more undue harm than these policymakers realize.

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1. Querdasi, F.R., Vogel, S.C., Thomason, M.E. et al. A comparison of the infant gut microbiome before versus after the start of the covid-19 pandemic. Sci Rep 13, 13289 (2023). https://doi.org/10.1038/s41598-023-40102-y

2. Roswell, M., Dushoff, J. and Winfree, R. (2021), A conceptual guide to measuring species diversity. Oikos, 130: 321-338. https://doi.org/10.1111/oik.07202

3. Lozupone, C., Lladser, M. E., Knights, D., Stombaugh, J., & Knight, R. (2011). UniFrac: an effective distance metric for microbial community comparison. The ISME journal, 5(2), 169–172. https://doi.org/10.1038/ismej.2010.133

4. Musher DM. Haemophilus Species. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 30. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8458/