In this study, we found the differential frailty status of elderly resident wasassociated with different their indoor microbial classification levels, which further clarified the characteristics of the microbial flora of spouses with different frailty states, including Cellulosimicrobium, Corynebacteriaceae, and Pleosporales. We further confirmed seven bacterial genera and five fungal genera related to the frailty of elderly residents. These potentially dangerous and/or protective species were strongly associated with environmental factors (living area) and frailty in elderly residents.
Relationship between indoor microbiota and frailty
We found that the level of chao1and richness in Alpha diversity were increased with the multiplication of frailty degree; however, the Simpson index results were decreased in results for bacteria and fungi. In addition, we found that the differences in the frailty of both spousal groups did not affect the structure of the microbiota (Beta diversity). We speculated this observation may be related to the fact that the subjects of this study were all located in the same village, and houses with similar outdoor environments also had similar microbial community structures [32]. Therefore, no differences in the bacterial community structure were observed between the groups in our study.
Pseudomona, Cellulosimicrobium, Chryseomicrobium, Brevibacterium, Aerococcus, Lodderomyces, and Trichoderma were potentially dangerous bacteria in association with the frailty state of the occupants. Moreover, the relative abundance of the above-mentioned bacteria was higher for spouses who were both frail. Frailty is a predisposing and immunocompromised biological syndrome that widely occurs in older adults[13], and is associated with a high incidence of infection and adverse clinical outcomes[33, 34]. Both Pseudomona and Cellulosimicrobium can cause serious infections in immunocompromised patients, including bacteremia [35] and infectious pneumonia [36]. Lodderomyces and Trichoderma are widespread fungi occurring in nature and are potential opportunistic pathogens associated with inflammation and infection in immunocompromised hosts [37, 38]. Moreover, frail individuals are at a higher risk of developing urinary tract infections due to an immunocompromised status [39], and infectious arthritis compared to younger adults [40, 41]. Brevibacterium and Aerococcus are common pathogens in urinary tract infections [42], of which Aerococcus is also a common pathogen causing joint infections [43]. Therefore, these results indicate that most of the potentially dangerous bacteria we have identified may have the potential to promote frailty. We also noted that among the potentially hazardous bacteria, a gram-positive genus that is often found in sediment/sludge is Chryseomicrobium [44, 45]; a potentially dangerous genus that has not been identified in previous studies.
Brevibacillus was found to be a potentially protective genus regarding the frailty status of the elderly occupants and had the lowest relative abundance in the group containing both frail spouses. Brevibacillus is a widely occurring genus in nature that is pathogenic to invertebrates [46]; however, its addition to mammalian feed has a prebiotic effect [47], and also functions as an antibacterial species with clinical potential [48]. Thus, Brevibacillus may be represent a new threshold to improve the frailty status of elderly occupants.
Remarkably, we found intergroup-specific flora in both Lefse analyses of bacteria and fungi. Cellulosimicrobium and Corynebacteriaceae in Actinobacteria were bacterial-specific colonies of both frailty spouses. Both of these strains can cause severe infections in immunocompromised patients [35, 49–51]. Among them, Cellulosimicrobium is also a dangerous bacteria genus that was screened through a regression analysis. In the group containing one frail spouse, a specific fungal marker was noted: the human infectious pathogen of the order Plosporales[52], which has also been significantly associated with the differential status of periodontitis [53]. Moreover, chronic periodontitis has been found to double the risk of developing Alzheimer's disease [54], and affect frailty status [55]. We believe that there is also a close link between the specific microflora and the frailty status of elderly occupants. Further studies are warranted to confidently determine the precise mechanism(s) of action of these microbiotas in frailty.
Relationship between indoor microbiota and environmental factors
A small living area was identified to be a risk factor for the frailty status of elderly occupants, and a decrease in living area was associated with an increase in the relative abundance of potentially dangerous bacteria. Importantly, the living area also reflects the economic situation of the occupants, and the larger the living area, the more conducive to lighting and ventilation, which has a beneficial impact on human health [56]. Previous studies have demonstrated that the increase in living area can provide sufficient growth space for the microflora, promote growth of the flora, and help increase the diversity of the bacterial community [57, 58]. Conversely, our study found that the increase in living area was inversely correlated with an increased relative abundance of dangerous strains and was positively correlated with an increased relative abundance of protective strains. We believe that this finding was attributed to the two-way relationship between the occupant and indoor microorganisms [20]. When the frailty status of the elderly occupants becomes aggravated, it is possible that more dangerous bacteria are released into the indoor environment. In turn, these dangerous bacterial strains will affect the elderly occupants. However, the specific causal relationship requires further exploration.
Low artificial illumination represents a risk factor for the frailty status of elderly occupants. Most of the changes in the bacterial community structure observed in the CCA analysis in this study were caused by artificial illuminance and may even cause changes in other environmental factors. Artificial illuminance has previously been shown to affect microbial diversity [59], which is consistent with the results of this study. For occupants, artificial illumination can significantly affect their aging and longevity [60]. Since artificial illumination refers more to night illumination, and insufficient illumination at night is one of the important reasons that the elderly fall [61], falls can lead to the onset or further exacerbate frailty among the elderly [62, 63]. It is important to note that in addition to the external triggers (e.g., insufficient illuminance), the risk factors for falling are also intrinsic (physical and psychological), meaning that the frailty status may also be the cause of the fall [64, 65]. Therefore, the impact of artificial illumination on the frailty status of elderly residents warrants attention, and the mechanism by which it affects aging and longevity is conducive to the formation of lighting standards suitable for the elderly population.
Advantages of this study
This study has several strengths. First, the use of a population-based, microbiome-wide association analysis afforded high statistical power to identify associations that have not been previously identified. Moreover, this was the first study to reveal indoor microbiota exposure, indoor environmental characteristics, and the frailty state of older occupants. Another advantage was that we grouped the different frailty status in the same household couple at the same village. Identifying the flora and environmental factors that affect changes in the frailty status through this initial frailty level division provides a unique perspective by which the results of the indoor microbiome can be explained. In addition, the frailty range was calculated by converting the binary classification into three classification data with a hierarchical progressive relationship, and converting the classified data into semi-quantitative data, the information that can be presented as more scientific and accurate. We also used a causal mediation analysis to explore the association between indoor microbiota exposure, indoor environmental characteristics, and the frailty status of elderly occupants. The results showed that indoor microorganisms had a certain influence on the association between indoor environmental characteristics and the frailty status of elderly occupants, which provided further insights into understanding the interaction between the three.
Limitations of this study
Our sample size was relatively small; we conducted the survey in one location only (Songmushan Village, Dalang Town, Dongguan City), and the results had certain limitations. Another limitation was that indoor microorganisms and occupants were mutually influential. However, our study was a cross-sectional study, which failed to reveal the causal effect of indoor microorganisms and occupants. Further research is required to identify the association between microbiota and human health status.