Impact of Probiotic Combination in InR[E19]/TM2 Drosophila melanogaster on Longevity, Related Gene Expression, and Intestinal Microbiota: A Preliminary Study

Abstract

The insulin receptor (InR) pertains to the insulin receptor family, which plays a key role in the insulin/insulin-like growth factor (IGF)-like signaling (IIS) pathway. Insulin signaling defects may result in the development of metabolic diseases, such as type 2 diabetes, and the InR mutant has been suggested to bear insulin signaling deficiency. Numerous studies have reported that probiotics are beneficial for the treatment of diabetes; however, the effect of probiotics on patients with InR deficiency has seldom been reported. Therefore, we chose the InR[E19]/TM2 Drosophila melanogaster to investigate. The results indicated that probiotics significantly reduce the mean and median lifespan of InR[E19]/TM2 Drosophila (by 15.56% and 23.82%, respectively), but promote that of wild-type files (by 9.31% and 16.67%, respectively). Significant differences were obtained in the expression of lifespan- and metabolism-related genes, such as Imp-L2, Tor, and GstD2, between the standard diet groups and the probiotics groups. Furthermore, analysis of 16S rDNA via high throughput sequencing revealed that the gut bacterial diversity of Drosophila fed with a probiotic combination also differs from that of Drosophila fed with a standard diet. In summary, these findings indicate that a probiotic combination indeed affects InR[E19]/TM2 Drosophila, but not all of its impacts are positive.

Treatment with Bacterial Biologics Promotes Healthy Aging and Traumatic Brain Injury Responses in Adult Drosophila, Modeling the Gut–Brain Axis and Inflammation Responses

“…Untreated flies showed the normal NGR decline, while only one week of LGG or IAB exposure helped maintain climbing behaviors ( Figure 5 B, Supplementary Table S4A ). Longevity studies also revealed that early IAB treatment (one week, 1:800) promoted longevity, while middle-aged flies treated with either biologic had increased lifespans ( Figure 5 C, Supplementary Table S4B ) [ 3 , 21 , 22 ].…”

“…Recent studies have shown that even modest OS level changes, including the production of reactive oxygen/nitrogen species, can further exacerbate inflammation in the neural tissues [ 13 , 15 , 16 , 17 ]. Indeed, elevated OS levels, cytokine imbalances, and glial activation can further damage neural tissue, accelerating neurodegenerative disease [ 18 , 19 , 20 , 21 , 22 ]. Identifying treatments that lower OS levels and promote cellular homeostasis would be beneficial for a range of maladies related to ageing or progressive cellular damage ( Supplementary Figure S1A,B ) [ 13 , 16 , 17 , 23 ].…”

“…Complicating most human-based studies are compliance issues, leading to non-uniform administration and dosing regimens [ 28 , 30 , 33 , 34 , 35 ]. Therefore, how ingested probiotics illicit neurological responses requires a high throughput model organism, like Drosophila, that has established gut–brain axis interactions [ 3 , 6 , 22 , 25 , 26 , 36 ].…”

“…In this report, a series of in vivo Drosophila studies were conducted to examine the impact that IAB and probiotic treatments have on the mature gut–brain axis. Existing Drosophila neural aging and TBI platforms were used to look at health, immunity, and longevity profiles of adult flies [ 7 , 9 , 10 , 11 , 12 , 13 , 14 , 22 , 24 , 41 , 42 , 43 ]. This work served as a preliminary assessment of bacteriologic interactions with gut and neural tissues, providing unique insights in to conserved mechanisms that IAB or probiotic treatments have on gut–brain axis interactions, as well as the ability to lower inflammation and OS levels and promote healthy aging and neuronal function [ 16 , 18 , 28 , 32 , 37 , 44 ].…”

Young at Gut—Turning Back the Clock with the Gut Microbiome

“…In aging rats, probiotics modulate AMPK activity and prevent telomere shortening [ 116 ]; protect aging bone and muscle [ 117 ]; and improve lipid, renal, and liver profiles, while also inhibiting the growth of pathogens Escherichia coli , Staphylococcus aureus , and Staphylococcus epidermidis [ 118 ]. However, in wild-type Drosophila melanogaster, although a probiotic mixture increases mean and median lifespan, it decreases mean and median lifespan in Drosophila melanogaster with insulin receptor deficiency and a type 2 diabetes mellitus phenotype [ 119 ]. These preliminary studies suggest that although probiotics may impact pathways involved in longevity, they may not universally prolong lifespan, and thus, more work is required to distinguish factors associated with the utility or possible harm of probiotics.…”