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Page 8 of 35 Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05

but not men. No differences in bacterial diversity were found among men and women, nor the non-
stratified obese and non-obese groups. Another large cross-sectional study of obese, overweight, and
healthy-weight adult Americans found a global association between BMI and microbiota richness, while
observing a reduction in richness in obese women compared to healthy-weight women, which was not
found in men . Although there was no trend observed between the F/B ratio and BMI, several sub-taxa
[57]
were associated with obesity compared to healthy-weight subjects, including enriched Streptococcaceae,
Lactobacillaceae, Actinomycetaceae, and Enterobacteriaceae families and decreased Christensenellaceae,
among other Clostridiaceae families. Moreover, overweight individuals showed similar gut microbial
composition as obese individuals.

The impact of weight loss following dietary (i.e., energy-restricted) or surgical intervention on the gut
microbiota has also been assessed. A systematic review and meta-analysis recently performed by
Koutoukidis et al. included trials of weight loss interventions in overweight or obese adults on an
[58]
international scale (i.e., 17 countries across five continents) . Findings reported an overall increase in
α-diversity with weight loss, with clear evidence for RYGB and inconsistent evidence for dietary
interventions. At the phylum level, a lower F/B ratio and enriched levels of Proteobacteria and
Verrucomicrobia following weight loss were reported, although the changes were not significant. However,
the abundance of Akkermansia, Bacteroides, and Bifidobacterium genera increased with weight loss, while
there was no evidence of changes in the presence of Lactobacillus. Reduced intestinal permeability with
weight loss was also reported, but no change in intestinal inflammation was found. Changes to the gut
microbiota with weight loss did not differ between types of intervention. In addition, differences in
microbiota-related metabolites after bariatric surgery, RYGB, or sleeve gastronomy (SG) have been
[59]
analyzed . Data suggest that the metabolite p-cresol increases after SG compared to RYGB, which may be
due to increased levels of Bacteroides with weight loss, which is one of the genera that ferments amino acids
phenylalanine and tyrosine to produce p-cresol.

Gut dysbiosis in obese-aged (i.e., aged 60 and older) compared to healthy-aged older adults was recently
reviewed by Tavassol et al. Cross-continental data revealed a decreased abundance of the
Christensenellaceae family and a higher abundance of Prevotella, order Clostridiales Incertae Sedis XIII,
[60]
Ruminococcus and Staphylococcus in obese-aged individuals . In other studies, Akkermansia, Clostridium,
Clostridiales and Ruminococcus-1 were negatively associated with obesity. For individuals with metabolic
syndrome, BMI and abundance of Prevotella were negatively associated. The authors explained the
discrepancies between Prevotella and Ruminococcus genera through their association with obesity in
western populations, but leanness in eastern cohorts. Similar reasoning can be applied to other
inconsistencies found in literature, given the significant influence of diet and environmental factors on gut
microbiota composition, as discussed above. Nevertheless, many of these findings are aligned with those
from obese or aged cohorts, suggesting a similar trend in gut microbiota alterations as a result of obesity,
aging, or their comorbidity.

The process of aging may disrupt gut homeostasis through a variety of factors, such as a weak immune
response (e.g., via dendritic cell dysfunction), repeated exposure to antibiotics, decreased intestinal motility,
and less nutrient turn-over, as well as altered diets to accommodate reduced chewing strength [45,61,62] .
Moreover, numerous age-related diseases are associated with gut dysbiosis. A recent meta-analysis
compared the gut microbiota in AD patients to that in individuals with mild cognitive impairment and
healthy elders . Findings show that individuals with AD but not cognitive impairment have reduced
[63]
bacterial α-diversity compared to healthy controls. Moreover, AD patients harbor enriched levels of
Proteobacteria and less abundance of Firmicutes. A trend toward decreased abundance of Clostridiaceae is