The mounting evidence of a causal role of the gut microbiota in multiple disease conditions has led to the development of targeted therapeutic approaches designed to alter the microbial composition.

Germ-free conditions have also been found to be protective against the development of colitis and ileitis in IBD-like mouse models with disease transmission only occurring after transfer of a dysbiotic gut microbiota ( Sellon et al., 1998 Schaubeck et al., 2016). In the case of obesity, the metabolic phenotype of the donor, be it lean or obese, can be recapitulated by a fecal microbiota transfer into germ-free mice ( Ridaura et al., 2013). The use of germ-free mice, which are born and raised in a sterile environment, play a pivotal role in demonstrating causative associations between the gut microbiota and disease ( Balish and Warner, 2002 BГ¤ckhed et al., 2004 Berer et al., 2011). However, evidence that the dysbiosis is causal in the development of these conditions remains difficult to establish, in all but a few cases. Observations of microbial dysbioses are increasingly being associated with a broad range of human diseases, including allergies ( Penders et al., 2007 Bunyavanich et al., 2016), asthma ( Arrieta et al., 2015), inflammatory bowel disease (IBD) ( Fujimoto et al., 2013 Gevers et al., 2014 Takahashi et al., 2016 Nishino et al., 2018), irritable bowel syndrome (IBS) ( Liu et al., 2017), obesity ( Schwiertz et al., 2010), and cardiovascular disease ( Cui et al., 2017 Jie et al., 2017). Typically, gut dysbiosis is characterized by a low microbial diversity ( Kriss et al., 2018).

An alteration to the microbiota that is associated with negative functional outcomes on gut physiology, such as localized inflammation or disturbed metabolic processing, is known as gut dysbiosis ( Petersen and Round, 2014). Despite this, it is generally accepted that having a stable and diverse gut community correlates with a healthy intestinal state ( Lloyd-Price et al., 2016). In a healthy adult, the bacterial population within the gut predominantly consists of members from the strictly anaerobic Firmicutes and Bacteroidetes phyla, with minor representations from members of the Proteobacteria and Actinobacteria phyla ( Eckburg et al., 2005 Ley et al., 2008).Д«ecause no two gut microbiomes are identical, the definition of what comprises a healthy gut microbiome from an inventory standpoint remains unclear ( Human Microbiome Project Consortium, 2012). The composition of the gut microbiota is shaped by both genetic and environmental influences, through a continual process that may begin in utero ( Perez-MuГ±oz et al., 2017) and fluctuates throughout an individual's lifetime ( Odamaki et al., 2016). Despite the variability between individuals, it is clear that the composition and functionality of the gut microbiota associates with the health of the host, having specialized functions in nutrition, energy metabolism, immune development, and host defense ( Thursby and Juge, 2017). The human gut harbors an abundant and diverse microbial community that is as unique to an individual as a fingerprint ( Human Microbiome Project Consortium, 2012). Finally, we discuss the potential long-term applicability of FMT for chronic disease and highlight how super-donors could provide the basis for dysbiosis-matched FMTs. Possible effects of host-genetics and diet on FMT engraftment and maintenance are also considered. Here, we review the evidence for super-donors in FMT and explore the concept of keystone species as predictors of FMT success. The identification and subsequent characterization of super-donor gut microbiomes will inevitably advance our understanding of the microbial component of chronic diseases and allow for more targeted bacteriotherapy approaches in the future. Notably, a number of studies suggest that FMT success is dependent on the microbial diversity and composition of the stool donor, leading to the proposition of the existence of FMT super-donors. Meanwhile the efficacy of FMT for treating chronic diseases associated with microbial dysbiosis has so far been modest with a much higher variability in patient response.

2The Broad Institute of MIT and Harvard, Cambridge, MA, United StatesДЇecal microbiota transplantation (FMT) has become a highly effective bacteriotherapy for recurrent Clostridium difficile infection.

1The Liggins Institute, University of Auckland, Auckland, New Zealand.

Cdiff super strain