15.3

Age-Related Changes in Gut Microbiota Depict Health

Status in the Elderly

Trillions of microorganisms or “microbial bank” of a diverse nature inhabit the

human GI tract. All the microbes harboring the gut are collectively known as “gut

microbiota,” and their associated genomes represent the “gut microbiome.” The GI

bacterial load in a healthy adult is estimated to be around 3
10¹³ bacterial cells in a

70-kg adult (Sender et al. 2016). The major bacterial phyla consist of Bacteroidetes

and Firmicutes and subgroups like Fusobacteria, Cyanobacteria, Proteobacteria,

Verrucomicrobia, Actinobacteria, and few others (Clemente et al. 2012). With

advancing chronological age, the gut microbiota become more diverse and variable

(Kim and Jazwinski 2018). Maffei et al. (2017) found that increasing biological age

is associated with gastrointestinal dysbiosis. In healthy adults, intestinal microbiota

is relatively stable throughout adulthood, but with ageing drastic changes occur due

to exogenous factors such as antibiotics use, dietary factors, and endogenous cellular

stress. In older adults (>63–76 years), gut microbiota become unstable affecting

intestinal motility and digestion. Variations in the GI microbiota adversely impact on

the fermentation processes leading to immunosenescence and low-grade inflamma-

tory responses in the gut.

The GI tract is mostly sterile in the intrauterine stage. However, Corynebacterium

sp. is usually the early colonizers in C-section babies and Lactobacillus sp. in the

vaginal delivery. With time the commensal bacterial community grows under the

influence of solid food intake. During the initial stages of microbiota establishment,

the Toll-like receptor (TLR) actions are minimal allowing growth of commensals.

Eventually, the immune system develops by demarking the pathogens and

commensals. Bacteroidetes dominate after 2 years of birth. The relative stability is

attained at adulthood by the domination of Bacteroidetes and Firmicutes. Significant

alterations occur with the use of antibiotics, obesity, GI disorders, and diet. With

advancing age, the microbiota stability declines, and commensal community of

Bacteroidetes and Firmicutes species decreases, and pathogenic species like Clos-

tridium increase. Therefore, gut microbial dysbiosis along with malnutrition, alcohol

abuse, decline in body metabolism, frequent hospitalization, and nasopharyngeal

and lung infections lead to polypharmacy and ultimately causing iatrogenic-related

diseases in the elderly individuals (Vemuri et al. 2018).

Biagi et al. (2010) have investigated functional differences in the gut microbiota

metagenome across different age groups—young adults, older adults, and

centenarians—using illumine shotgun sequencing on fecal samples. It was observed

that the proteolytic activity was increased accompanied by a clear loss in the genes

associated with the carbohydrate metabolism with ageing. Short-chain fatty acid

(SCFA) production also declined due to the age-related reduction of genetic

pathways caused by microbiome rearrangement. The authors concluded that manip-

ulation of the intestinal microbiota and microbiome may be beneficial for

maintaining health and treating age-related disorders (Biagi et al. 2010). Circadian

rhythm, metabolism, and gut microbiota are intricately linked with each other. Most

of the glucose tolerance occurs during sleep, influencing nocturnal brain and tissue

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The Importance of Drug Dose Adjustment in Elderly Patients with Special. . .

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