Decreased microbial co-occurrence network stability and SCFA receptor level correlates with obesity in African-origin women

Abstract

We compared the gut microbial populations in 100 women, from rural Ghana and urban US [50% lean (BMI < 25 kg/m2) and 50% obese (BMI ≥ 30 kg/m2)] to examine the ecological co-occurrence network topology of the gut microbiota as well as the relationship of short chain fatty acids (SCFAs) with obesity. Ghanaians consumed significantly more dietary fiber, had greater microbial alpha-diversity, different beta-diversity, and had a greater concentration of total fecal SCFAs (p-value < 0.002). Lean Ghanaians had significantly greater network density, connectivity and stability than either obese Ghanaians, or lean and obese US participants (false discovery rate (FDR) corrected p-value ≤ 0.01). Bacteroides uniformis was significantly more abundant in lean women, irrespective of country (FDR corrected p < 0.001), while lean Ghanaians had a significantly greater proportion of Ruminococcus callidus, Prevotella copri, and Escherichia coli, and smaller proportions of Lachnospiraceae, Bacteroides and Parabacteroides. Lean Ghanaians had a significantly greater abundance of predicted microbial genes that catalyzed the production of butyric acid via the fermentation of pyruvate or branched amino-acids, while obese Ghanaians and US women (irrespective of BMI) had a significantly greater abundance of predicted microbial genes that encoded for enzymes associated with the fermentation of amino-acids such as alanine, aspartate, lysine and glutamate. Similar to lean Ghanaian women, mice humanized with stool from the lean Ghanaian participant had a significantly lower abundance of family Lachnospiraceae and genus Bacteroides and Parabacteroides, and were resistant to obesity following 6-weeks of high fat feeding (p-value < 0.01). Obesity-resistant mice also showed increased intestinal transcriptional expression of the free fatty acid (Ffa) receptor Ffa2, in spite of similar fecal SCFAs concentrations. We demonstrate that the association between obesity resistance and increased predicted ecological connectivity and stability of the lean Ghanaian microbiota, as well as increased local SCFA receptor level, provides evidence of the importance of robust gut ecologic network in obesity.

Short Chain Fatty Acids and Fecal Microbiota Abundance in Humans with Obesity: A Systematic Review and Meta-Analysis

“…After we further examined the 29 identified articles, 22 articles were excluded (Supplementary Table S2). Finally, we identified seven articles that met the inclusion criteria [8,9,10,11,13,24,25]. The overall quality of the studies averaged eight stars (range, 7–9) on a scale from zero to nine stars (Supplementary Table S3).…”

“…All of the studies were published from 1993 to 2018. Three studies were conducted in Canada [8,9,25], three in Europe [10,11,13], and one in the United States and Ghana [24]. The participants’ ages ranged from 6 to 74 years old.…”

“…The overall number of obese cases was 246, and the number of nonobese controls was 198. Six studies [8,9,11,13,24,25] measured obesity using the body mass index (BMI), and one study [10] measured obesity using the BMI-Z score. Of the included studies, six measured SCFA status through the analysis of feces [8,9,10,11,13,24] and one measured SCFA status through the analysis of serum [25].…”

“…Five studies used gas chromatography [8,9,13,24,25], one used capillary electrophoresis [10], and one used liquid chromatography [11]. Microbiology was assessed using quantitative polymerase chain reaction (qPCR) or real-time qPCR in five studies [8,9,10,13,24,25]. One study used PCR and restriction enzyme length polymorphism analysis [11].…”

“…One article reported the data stratified by level of overweight (BMI >25 kg/m 2 ) and obese (BMI >30 kg/m 2 ) [13]. One article reported each dataset from the United States and Ghana [24]. In addition, four of the included studies reported fecal microbiota richness in obese and nonobese individuals [8,9,10,13].…”