Background Most studies investigating human gut microbiome dynamics are conducted on humans living in an urban setting. However, few studies have researched the gut microbiome of the populations living traditional lifestyles. These understudied populations are arguably better subjects in answering human-gut microbiome evolution because of their lower exposure to antibiotics and higher dependence on natural resources. Hadza hunter-gatherers in Tanzania have exhibited high biodiversity and seasonal patterns in their gut microbiome composition at the family level, where some taxa disappear in one season and reappear later. Such seasonal changes have been profiled, but the nucleotide changes remain unexplored at the genome level. Thus, it is still elusive how microbial communities change with seasonal changes at the genome level. Results In this study, we performed a strain-level single nucleotide polymorphism (SNP) analysis on 40 Hadza fecal metagenome samples spanning three seasons. With more SNP presented in the wet season, eight prevalent species have significant SNP enrichment with the increasing number of SNP calling by VarScan2, among which only three species have relatively high abundances. Eighty-three genes have the most SNP distributions between the wet season and dry season. Many of these genes are derived from Ruminococcus obeum, and mainly participated in metabolic pathways including carbon metabolism, pyruvate metabolism, and glycolysis. Conclusions Eight prevalent species have significant SNP enrichments with the increasing number of SNP, among which only Eubacterium biforme, Eubacterium hallii and Ruminococcus obeum have relatively high species abundances. Many genes in the microbiomes also presented characteristic SNP distributions between the wet season and the dry season. This implies that the seasonal changes might indirectly impact the mutation patterns for specific species and functions for the gut microbiome of the population that lives in traditional lifestyles through changing the diet in wet and dry seasons, indicating the role of these variants in these species’ adaptation to the changing environment and diets.
Background Lactose malabsorption occurs in around 68% of the world’s population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal β-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal β-galactosidase activity and influence intestinal homeostasis. Results Here, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of β-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and β-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated. Conclusions Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain β-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.
BackgroundLactose malabsorption occurs in around 68% of the world populations, causing lactose intolerance (LI) symptoms such as abdominal pain, bloating and diarrhoea. To alleviate LI, previous studies mainly focused on strengthening intestinal β-galactosidase activity but neglected the inconspicuous colon pH drop caused by gut microbes’ fermentation on non-hydrolysed lactose. The colon pH drop will reduce intestinal β-galactosidase activity and influence the intestinal homeostasis.ResultsHere, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between expression of β-galactosidase and expression of l-lactate dehydrogenase in respond to intestinal lactose signal and intestinal pH signal. We confirmed the circuit functionality was efficient using 12-hrs in vitro culture at a range of pH levels, as well as 6-hrs in vivo simulations in mice colon. Moreover, another 21-days mice trial indicated that this circuit can recover lactose-effected gut microbiota of mice to the status (enterotypes) similar to that of mice without lactose intake.ConclusionsTaken together, the tri-stable-switch circuit can serve as a promising prototype for LI symptoms relief, especially by flexibly adapting to environmental variation, stabilizing colon pH and restoring gut microbiota.
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