Page 53 - Read Online

Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05 Page 7 of 35

(GLP-1), polypeptide YY (PYY), and cholecystokinin (CCK) are well-known satiety hormones. After
ingestion of fats and carbohydrates, EECs in the ileum and colon release GLP-1 and PYY to delay the
transport of nutrients from the stomach into the small intestine (i.e., gastric emptying), enabling optimal
digestion and absorption of nutrients. GLP-1 also stimulates the secretion of glucose-dependent insulin,
while PYY increases water and ion absorption in the colon and prevents their secretion. Produced in the
small intestine, CCK also delays gastric emptying, stimulates the release of bile and pancreatic enzymes (e.g.,
intestinal lipase) and transmits satiety signals to the central nervous system (CNS) via vagal afferents. The
GI is innervated by intrinsic neurons of the enteric nervous system (ENS) and axons of the extrinsic
sympathetic, parasympathetic (e.g., vagus nerve), and visceral afferent neurons . The anatomy of the GI
[43]
enables bi-directional communication to the CNS, known as the gut-brain axis (GBA). The three main
mediators of the GBA include neuronal messages carried by vagal afferents, endocrine messages carried by
gut hormones, and immune messages carried by cytokines.

Gut dysbiosis in obesity and aging
The human GI tract is home to a huge and complex microbial ecosystem made up of trillions of
[44]
microorganisms, including bacteria, fungi, parasites, and viruses . This community, known as the gut
microbiota, plays an imperative role in human health and disease. A healthy gut microbiota is required for
nutrient metabolism, immunomodulation, protection against pathogens and integrity of the GI tract. The
majority of the microbiota belong to the gram-positive phylum Firmicutes (~51%) and gram-negative
phylum Bacteroidetes (~48%), necessitating a delicate balance between them, known as the Firmicutes to
Bacteroidetes (F/B) ratio. The remaining 1% of the gut microbiota is constituted by other less populous
a
p h y l a , i n c l u d i n g Proteobacteria, Actinobacteria, Fusobacteria, Spirochaetes, Verrucomicrobia, n d
Lentisphaerae. It is well-known that the gut microbiota changes throughout one’s lifespan and reaches
relative stability in adulthood . However, alterations to the gut microbiota, known as microbial dysbiosis,
[45]
[43]
may occur and are characterized by changes to local bacterial composition or bacterial metabolic activity .
Given its central role in the GI system, the gut microbiota is largely influenced by dietary habits. For
example, a high-fat diet (HFD) or a diet rich in animal proteins can impair gut eubiosis. In fact, germ-free
mice are protected against diet-induced obesity associated with a Western, high-fat and high-sugar diet,
compared to mice with a gut microbiota . Moreover, diet differs based on geographical factors, which is
[46]
reflected by varying gut compositions of similar cohorts from different populations. These notions and the
[47]
significance of dietary factors on the gut microbiota have been reviewed in detail previously . Lifestyle, age,
disease, cognitive function, antibiotic treatment, and numerous other factors can also modulate the
microbiota, triggering dysbiosis .
[48]
A comparison of gut composition and function associated with obesity and aging is critical for the
discussion of their proposed interrelationship. Evidence of gut microbial alterations in obese individuals is
[50]
[49]
well-established . However, a dysbiotic gut has only recently been recognized as an aging hallmark .
There are general trends in literature regarding gut microbial alterations associated with obesity or aging,
including a relatively higher F/B ratio and reduced bacterial α-diversity (i.e., richness and complexity of the
microbial ecosystem) [51-54] . However, a clearly defined microbial profile for either obesity or aging, among
most diseases, has not yet reached a consensus . Population-based studies have been conducted to better
[55]
understand microbiota shifts associated with these diseases. A cross-continental systematic review discussed
gut microbiota differences in obese individuals from Europe, America, and Asia . Briefly, obese individuals
[56]
from Japan and France display a higher F/B ratio compared to their non-obese counterparts. Within the
Firmicutes phylum, the abundance of Christensenellaceae family is significantly higher in individuals with a
lean BMI compared to those with an obese BMI, according to a study performed in twin pairs from the UK.
Interestingly, investigation of overweight or obese individuals with cardiovascular disease emphasized the
impact of gender and BMI on the F/B ratio, reporting an increased F/B ratio correlated with BMI in women