Inner workings of infant gut

Gut microbiota-derived metabolites in early life can be promising targets for manipulating subsequent host health. Tsukuda and Yahagi et al. investigated infant gut ecosystem development intensively, finding key bacterial taxa and metabolic pathways that influence gut SCFA profile in early life.

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How is the gut microbiome established? This question first came to my mind as I changed my baby children’s diapers. Over time, I observed a drastic change in the colour and smell of their faeces, indicating that dynamic and fast-paced changes were taking place. To explore this phenomenon, we undertook a research project.

In the past decade, many studies have focused on infant gut microbiota development1 and its association with subsequent host health and disease2. Moreover, recent studies have demonstrated that short-chain fatty acids (SCFAs) are key metabolites that mediate symbiotic microbiota-host relationships3. In this study, we investigated gut SCFA dynamics, equilibria, and their association with gut microbiota, using a total of 1,048 samples collected over 2 years from 12 infants.

We found that early-life gut microbiota can be divided into three clusters and observed sequential transitions occurring from Enterobacterales- to Bifidobacteriales-, and then to Clostridiales-dominant microbiota. Analysis of metabolites revealed that the SCFA profiles also exhibited three distinct phases of progression: early-phase characterised by low acetate and high succinate, middle-phase characterised by high lactate and formate, and late-phase characterised by high propionate and butyrate.

We next evaluated the association among gut microbiota, SCFA profile, and life events, which revealed that cessation of breastfeeding induces the increase of Clostridiales abundance and butyrate concentration. We also found that early-life Clostridiales are diverse and personalised and possess sets of butyrate-producing genes.

Dynamics of gut short-chain fatty acid profile and their association with microbiota in early life. Both gut microbiota composition and SCFA profiles exhibit three phases of progression. Until breastfeeding cessation, colonisation of fucosylated human milk oligosaccharide-utilising bifidobacteria contribute to lactate and formate production. After the breastfeeding cessation, diverse and personalised Clostridiales play major roles in gut butyrate production.
Dynamics of gut short-chain fatty acid profile and their association with microbiota in early life. Both gut microbiota composition and SCFA profiles exhibit three phases of progression. Until breastfeeding cessation, colonisation of fucosylated human milk oligosaccharide-utilising bifidobacteria contribute to lactate and formate production. After the breastfeeding cessation, diverse and personalised Clostridiales play major roles in gut butyrate production.

Further, we found an association between gut formate concentration and abundance of some infant-associated bifidobacterial species: human milk oligosaccharide-derived fucose was involved in formate production during the breastfeeding period. We identified genes upregulated in fucose and fucosylated human milk oligosaccharide utilisation in infant-associated bifidobacteria. Notably, bifidobacterial species showed interspecific and intraspecific variation in their gene repertoires, and cross-feeding of fucose among bifidobacterial species contributed to gut formate production.

 To our knowledge, this is the first study demonstrating the production and accumulation of lactate and formate in breastfed infants. However, the physiological effects of these microbiota-derived metabolites are not clear. Our findings highlight the importance of elucidating the functional roles of these minor SCFAs. Additionally, gut microbiota-derived butyrate performs various health-promoting functions, including exerting protective effects against subsequent asthma risk4. Since the microbiota-derived SCFAs in early life are associated with subsequent host health4, the findings of our study pave the way to answer another question that came up in my mind: “Can we modulate the gut microbiome of our grandchildren to reduce their risk of disease in future?”    

Thank you for reading; the full paper being referred to here “Key bacterial taxa and metabolic pathways affecting gut short-chain fatty acid profiles in early life” is available at The ISME Journal: https://www.nature.com/articles/s41396-021-00937-7 

  1. Matsuki T, Yahagi K, Mori H, Matsumoto H, Hara T, Tajima S et al. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development. Nat Commun. 2016;7:11939.
  2. Stewart CJ, Ajami NJ, O'Brien JL, Hutchinson DS, Smith DP, Wong MC et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562:583-588.
  3. Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12:661-672.
  4. Depner M, Taft DH, Kirjavainen PV, Kalanetra KM, Karvonen AM, Peschel S et al. Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma. Nat Med. 2020;26:1766-1775.

Takahiro Matsuki

Group leader, Yakult Central Institute